FSH receptor

Target not currently curated in GtoImmuPdb

Target id: 253

Nomenclature: FSH receptor

Family: Glycoprotein hormone receptors

Gene and Protein Information
Previous and Unofficial Names
Database Links
Natural/Endogenous Ligands
Rank order lists
Agonists
Antagonists
Immuno Process Associations
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
General Comments
References
Contributors
How to cite this page

Gene and Protein Information
class A G protein-coupled receptor
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	7	695	2p16.3	FSHR	follicle stimulating hormone receptor	23
Mouse	7	692	17 E5	Fshr	follicle stimulating hormone receptor	32
Rat	7	692	6q12	Fshr	follicle stimulating hormone receptor	27

Previous and Unofficial Names
Follitropin receptor \| LGR1 \| FSH-R

Previous and Unofficial Names

Follitropin receptor | LGR1 | FSH-R

Database Links
Specialist databases
GPCRdb	fshr_human (Hs), fshr_mouse (Mm), fshr_rat (Rn)
Other databases
Alphafold	P23945 (Hs), P35378 (Mm), P20395 (Rn)
CATH/Gene3D	3.80.10.10
ChEMBL Target	CHEMBL2024 (Hs), CHEMBL4288 (Rn)
DrugBank Target	P23945 (Hs)
Ensembl Gene	ENSG00000170820 (Hs), ENSMUSG00000032937 (Mm), ENSRNOG00000016783 (Rn)
Entrez Gene	2492 (Hs), 14309 (Mm), 25449 (Rn)
Human Protein Atlas	ENSG00000170820 (Hs)
KEGG Gene	hsa:2492 (Hs), mmu:14309 (Mm), rno:25449 (Rn)
OMIM	136435 (Hs)
Orphanet	ORPHA121943 (Hs)
Pharos	P23945 (Hs)
RefSeq Nucleotide	NM_000145 (Hs), NM_013523 (Mm), NM_199237 (Rn)
RefSeq Protein	NP_000136 (Hs), NP_038551 (Mm), NP_954707 (Rn)
UniProtKB	P23945 (Hs), P35378 (Mm), P20395 (Rn)
Wikipedia	FSHR (Hs)

Natural/Endogenous Ligands
FSH {Sp: Human} , FSH {Sp: Mouse} , FSH {Sp: Rat}

Potency order of endogenous ligands
FSH (CGA, FSHB, P01215, P01225)

Potency order of endogenous ligands

FSH (CGA, FSHB, P01215, P01225)

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists

Key to terms and symbols

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Ligand	Sp.	Action	Value	Parameter
FSH {Sp: Human}	Hs	Agonist	-	-
⤷
[¹²⁵I]FSH (human)	Hs	Full agonist	-	-
⤷

Agonist Comments

The FSH receptor is the primary target of the approved drug urofollitropin, a recombinamt form of endogenous FSH.

Various cyclic and acyclic α and β aminocarboxamide derivatives (pK_d ∼ 8.4 - 5.8) [25], thiazolidine derivatives (pK_d ∼ 7.5) [21], biaryl derivatives (pK_d ∼ 8.15 - 7.5) [15-16] and thienopyrimidine derivatives (pK_d ∼ 7.4 - 6.0) [34] are known to be FSH receptor agonists.

Antagonists

Key to terms and symbols

Click column headers to sort

Ligand											Sp.	Action	Value	Parameter	Reference
FSH deglycosylated α/β											Hs	Antagonist	10.0	pK_d	13,19
⤷	pK_d 10.0 [13,19]

Antagonist Comments

Various aminoalkylamide derivatives (pIC₅₀ ∼ 7.0 - 4.3), tetrahydroquinoline derivatives (pIC₅₀ ∼ 6.0) [35] and arylsulfonic acids (pIC₅₀ ∼ 5.5)[5,28,37] are known to be FSH receptor antagonists.

Immuno Process Associations

Immuno Process:

Immune regulation

Immuno Process:

Immune system development

Primary Transduction Mechanisms
Transducer	Effector/Response
G_s family G_i/G_o family G_q/G₁₁ family	Adenylyl cyclase stimulation
Comments: In gonadal cells, the receptor primarily activates G_s. However, other G proteins and signaling pathways have been reported as being activated.
References: 14

Tissue Distribution

Placenta and Decidua

Species:	Human
Technique:	Immunohistochemistry, PCR
References:	29

Bone

Species:	Human
Technique:	Immunohistochemistry, Western blot and PCR
References:	8,38

Endothelium.

Species:	Human
Technique:	Immunohistochemistry, PCR
References:	29-30

Myometrium, Endometrium, and Cervix

Species:	Human
Technique:	Immunohistochemistry, PCR
References:	29

Testis.

Species:	Human
Technique:	in situ hybridisation.
References:	6

Endothelium.

Species:	Mouse
Technique:	Immunohistochemistry, PCR
References:	29-30

Testis.

Species:	Mouse
Technique:	in situ hybridisation.
References:	6

Bone

Species:	Mouse
Technique:	Immunohistochemistry, Western blot and PCR
References:	8,38

Myometrium, Endometrium, and Cervix

Species:	Mouse
Technique:	Immunohistochemistry, PCR
References:	29

Placenta and Decidua

Species:	Mouse
Technique:	Immunohistochemistry, PCR
References:	29

Ovary.

Species:	Rat
Technique:	QRT-PCR and in situ hybridisation.
References:	9

Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays

Measurement of steroidogeneis in rat testes endogenously expressing the FSH receptor.

Species:	Rat
Tissue:	Testes.
Response measured:	Steroidogenesis.
References:	20

Measurement of cAMP levels and steroidogenesis in rat granulosa cells of the ovary endogenously expressing the FSH receptor.

Species:	Rat
Tissue:	Granulosa cells of the ovary.
Response measured:	Stimulation of cAMP accumulation and steroidogenesis.
References:	2

Measurement of cAMP levels in rat Sertoli cells of the testis endogenously expressing the FSH receptor.

Species:	Rat
Tissue:	Sertoli cells of the testis.
Response measured:	Stimulation of cAMP production.
References:	36

Physiological Functions

Spermatogenesis.

Species:	Human
Tissue:	Testis.
References:	1,10

Folliculogenesis.

Species:	Human
Tissue:	Ovary.
References:	1,3-4,10,17

Physiological Consequences of Altering Gene Expression

FSH receptor knockout mice exhibit failure of ovarian follicles to mature beyond antral follicle as well as reduced testicular size without azoospermia.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	1,10

Phenotypes, Alleles and Disease Models

Mouse data from MGI

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Allele	Composition & genetic background	Accession	Phenotype Id	Phenotype	Reference
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0000010	abnormal abdominal fat pad morphology	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0002660	abnormal caput epididymis morphology	PMID: 10775161
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0002661	abnormal corpus epididymis morphology	PMID: 15973687
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0000812	abnormal dentate gyrus morphology	PMID: 14502087
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009094	abnormal endometrial gland morphology	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0005584	abnormal enzyme/coenzyme activity	PMID: 14502087
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0004933	abnormal epididymis epithelium morphology	PMID: 15973687
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0002631	abnormal epididymis morphology	PMID: 10775161
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001927	abnormal estrous cycle	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001927	abnormal estrous cycle	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0009016	abnormal estrus	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0006361	abnormal female germ cell morphology	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0000559	abnormal femur morphology	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0008868	abnormal granulosa cell morphology	PMID: 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0006362	abnormal male germ cell morphology	PMID: 10775161
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0008871	abnormal ovarian follicle number	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001130	abnormal ovarian folliculogenesis	PMID: 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001130	abnormal ovarian folliculogenesis	PMID: 12135868
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0002783	abnormal ovarian secretion	PMID: 10803590
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001126	abnormal ovary morphology	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001126	abnormal ovary morphology	PMID: 11089565 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0001126	abnormal ovary morphology	PMID: 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0003507	abnormal ovary physiology	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0006304	abnormal seminiferous epithelium morphology	PMID: 10775161 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0002216	abnormal seminiferous tubule morphology	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0006380	abnormal spermatid morphology	PMID: 10775161
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0006380	abnormal spermatid morphology	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001156	abnormal spermatogenesis	PMID: 10775161 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0006378	abnormal spermatogonia morphology	PMID: 10775161
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0002685	abnormal spermatogonia proliferation	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009838	abnormal sperm axoneme morphology	PMID: 15973687
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0008892	abnormal sperm flagellum morphology	PMID: 10775161 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009230	abnormal sperm head morphology	PMID: 15973687
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001932	abnormal spermiogenesis	PMID: 10775161
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0001932	abnormal spermiogenesis	PMID: 10775161
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001932	abnormal spermiogenesis	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009232	abnormal sperm nucleus morphology	PMID: 15973687
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0004543	abnormal sperm physiology	PMID: 10775161
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0004543	abnormal sperm physiology	PMID: 10775161
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0002782	abnormal testicular secretion	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0003830	abnormal testis development	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0004849	abnormal testis size	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0003047	abnormal thoracic vertebrae morphology	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0004014	abnormal uterine environment	PMID: 12193578
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001120	abnormal uterus morphology	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0001120	abnormal uterus morphology	PMID: 12193578
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001140	abnormal vagina epithelium morphology	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001142	abnormal vagina opening	PMID: 11089565
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001134	absent corpus luteum	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001134	absent corpus luteum	PMID: 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001134	absent corpus luteum	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001134	absent corpus luteum	PMID: 11089565 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0001134	absent corpus luteum	PMID: 14502087
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0009009	absent estrous cycle	PMID: 10803590
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0009009	absent estrous cycle	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009009	absent estrous cycle	PMID: 11089565 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0009009	absent estrous cycle	PMID: 12193578
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001132	absent mature ovarian follicles	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001132	absent mature ovarian follicles	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001132	absent mature ovarian follicles	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0004805	absent oocytes	PMID: 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0002777	absent ovarian follicles	PMID: 14502087
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001577	anemia	PMID: 11459817
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0008869	anovulation	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0008869	anovulation	PMID: 11459817
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0002675	asthenozoospermia	PMID: 10775161 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0002675	asthenozoospermia	PMID: 15973687
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0003354	astrocytosis	PMID: 14502087
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0005150	cachexia	PMID: 11459817
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0003195	calcinosis	PMID: 11459817
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0000063	decreased bone density	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0005181	decreased circulating estradiol level	PMID: 11089565 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0005181	decreased circulating estradiol level	PMID: 12193578 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0005185	decreased circulating progesterone level	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0005185	decreased circulating progesterone level	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0005185	decreased circulating progesterone level	PMID: 12193578
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0002780	decreased circulating testosterone level	PMID: 10775161 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0002780	decreased circulating testosterone level	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0002780	decreased circulating testosterone level	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0004929	decreased epididymis weight	PMID: 10775161
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0004929	decreased epididymis weight	PMID: 11466221
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0001935	decreased litter size	PMID: 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001935	decreased litter size	PMID: 11089565 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001935	decreased litter size	PMID: 11466221
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0001935	decreased litter size	PMID: 12193578
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0004856	decreased ovary weight	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0004856	decreased ovary weight	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0004910	decreased seminal vesicle weight	PMID: 10775161
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0004852	decreased testis weight	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0004852	decreased testis weight	PMID: 10775161
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0004852	decreased testis weight	PMID: 11466221
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0004905	decreased uterus weight	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0004905	decreased uterus weight	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0008980	decreased vagina weight	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0008976	delayed female fertility	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0008975	delayed male fertility	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001938	delayed sexual maturation	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009231	detached acrosome	PMID: 15973687
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0008995	early reproductive senescence	PMID: 11089565 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0008995	early reproductive senescence	PMID: 12193578 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0008994	early vaginal opening	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0008366	enlarged adenohypophysis	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0003529	enlarged clitoris	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0009251	enlarged endometrial glands	PMID: 12193578
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0009233	enlarged sperm head	PMID: 10775161
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0000691	enlarged spleen	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0004906	enlarged uterus	PMID: 12193578
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001926	female infertility	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001926	female infertility	PMID: 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001926	female infertility	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001926	female infertility	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0000811	hippocampal neuron degeneration	PMID: 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001505	hunched posture	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001505	hunched posture	PMID: 11089565
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001129	impaired ovarian folliculogenesis	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001129	impaired ovarian folliculogenesis	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001129	impaired ovarian folliculogenesis	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0001363	increased anxiety-related response	PMID: 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0006042	increased apoptosis	PMID: 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001260	increased body weight	PMID: 11089565 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001260	increased body weight	PMID: 11089565
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001750	increased circulating follicle stimulating hormone level	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001750	increased circulating follicle stimulating hormone level	PMID: 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0001750	increased circulating follicle stimulating hormone level	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001750	increased circulating follicle stimulating hormone level	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0001750	increased circulating follicle stimulating hormone level	PMID: 12193578
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001751	increased circulating luteinizing hormone level	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001751	increased circulating luteinizing hormone level	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0001751	increased circulating luteinizing hormone level	PMID: 12193578
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0002781	increased circulating testosterone level	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0002781	increased circulating testosterone level	PMID: 11089565 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0002781	increased circulating testosterone level	PMID: 12193578 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0002678	increased follicle recruitment	PMID: 12135868
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0005131	increased follicle stimulating hormone level	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0005131	increased follicle stimulating hormone level	PMID: 11459817
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0008334	increased gonadotroph cell number	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0005133	increased luteinizing hormone level	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0008000	increased ovary tumor incidence	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0003132	increased pre-B cell number	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0002797	increased thigmotaxis	PMID: 14502087
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0008337	increased thyrotroph cell number	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0008908	increased total fat pad weight	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0004904	increased uterus weight	PMID: 12193578
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0009237	kinked sperm flagellum	PMID: 10775161
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0000160	kyphosis	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0000160	kyphosis	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0002293	long gestation period	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009090	myometrium hypoplasia	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0002058	neonatal lethality	PMID: 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0002229	neurodegeneration	PMID: 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001261	obese	PMID: 11089565 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001261	obese	PMID: 11089565 11459817
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0002687	oligozoospermia	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0002687	oligozoospermia	PMID: 15973687
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0009093	oocyte degeneration	PMID: 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0003579	ovarian carcinoma	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0004833	ovary atrophy	PMID: 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0002016	ovary cysts	PMID: 11459817 12135868
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0002016	ovary cysts	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0002016	ovary cysts	PMID: 12193578 14502087
Fshr⁺\|Fshr^tm1Hht	Fshr^tm1Hht/Fshr⁺ involves: 129S7/SvEvBrd	MGI:95583	MP:0004834	ovary hemorrhage	PMID: 20172968
Fshr^tm1Hht	Fshr^tm1Hht/Fshr^tm1Hht involves: 129S7/SvEvBrd	MGI:95583	MP:0004834	ovary hemorrhage	PMID: 20172968
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0003717	pallor	PMID: 11459817
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0009433	polyovular ovarian follicle	PMID: 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0002082	postnatal lethality	PMID: 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0003786	premature aging	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0003786	premature aging	PMID: 14502087
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0009011	prolonged diestrus	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0009006	prolonged estrous cycle	PMID: 11089565 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0001923	reduced female fertility	PMID: 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129/Sv	MGI:95583	MP:0001923	reduced female fertility	PMID: 12135868
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0001923	reduced female fertility	PMID: 12193578
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001922	reduced male fertility	PMID: 10775161 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0001922	reduced male fertility	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001922	reduced male fertility	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0005250	Sertoli cell hypoplasia	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009248	small caput epididymis	PMID: 15973687
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0004930	small epididymis	PMID: 10775161
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001127	small ovary	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001127	small ovary	PMID: 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0001127	small ovary	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001127	small ovary	PMID: 11459817
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001157	small seminal vesicle	PMID: 10775161 9811848
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001153	small seminiferous tubules	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001153	small seminiferous tubules	PMID: 10775161 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001153	small seminiferous tubules	PMID: 11466221
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0001147	small testis	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0002637	small uterus	PMID: 9811848
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: C57BL/6	MGI:95583	MP:0002637	small uterus	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0005578	teratozoospermia	PMID: 15973687
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: C57BL/6	MGI:95583	MP:0009081	thin uterus	PMID: 9811848
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0009081	thin uterus	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0005048	thrombosis	PMID: 12193578
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0004898	uterine hemorrhage	PMID: 12193578
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0009221	uterus adenomyosis	PMID: 12193578
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0004894	uterus atrophy	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0004894	uterus atrophy	PMID: 11089565
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0009082	uterus cysts	PMID: 12193578
Fshr⁺\|Fshr^tm1Saco	Fshr^tm1Saco/Fshr⁺ involves: 129T2/SvEmsJ	MGI:95583	MP:0009222	uterus tumor	PMID: 12193578
Fshr^tm1Mha	Fshr^tm1Mha/Fshr^tm1Mha involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:95583	MP:0001144	vagina atresia	PMID: 10803590
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0004895	vagina atrophy	PMID: 11089565
Fshr^tm1Saco	Fshr^tm1Saco/Fshr^tm1Saco involves: 129/Sv	MGI:95583	MP:0001263	weight loss	PMID: 11459817

Clinically-Relevant Mutations and Pathophysiology

Disease:

Ovarian dysgenesis 1; ODG1

Synonyms:	46,XX gonadal dysgenesis [Orphanet: ORPHA243] [Disease Ontology: DOID:14450]
Disease Ontology:	DOID:14450
OMIM:	233300
Orphanet:	ORPHA243

Comments:

An A189V substitution in the extracellular ligand-binding domain resulting in impaired trafficking to the cell membrane. This receptor variant has been identified in humans suffering from hypergonadotropic ovarian dysgenesis (ODG).

References:

3-4,26

Click column headers to sort

Type	Species	Amino acid change	Nucleotide change	Description	Reference
Missense	Human	A189V			3-4,26

Disease:

Ovarian hyperstimulation syndrome

Disease Ontology:	DOID:5425
OMIM:	608115
Orphanet:	ORPHA64739

Comments:

A T449A mutation in the 3rd transmembrane results in a receptor with increased ligand sensitivity. This mutation has been identified in patients with ovarian hyperstimulation syndrome.

References:

Click column headers to sort

Type	Species	Amino acid change	Nucleotide change	Description	Reference
Missense	Human	T449A			24

Disease:

Primary ovarian failure

Synonyms:	Premature ovarian failure
Disease Ontology:	DOID:5426
Orphanet:	ORPHA619

Comments:

A D224V mutation in the extracellular domain of the receptor results in impaired targeting of the receptor to the cell membrane while a L601V mutation in the 3rd extracellular loop creates a receptor that bind ligands but has impaired signalling (Touraine et al., 1999). A P519T mutation in the 2nd extracellular loop of the receptor results in impaired targeting of the receptor to the cell membrane (Meduri et al., 2003). These mutations have been indentified in patients suffering from primary ovarian failure.

An A419T mutation in the 2nd transmembrane domain results in abolished adenylyl cyclase signalling, although has no effect on ligand binding. This mutation has been identified in a patient suffering from primary ovarian failure (Doherty et al., 2002).

References:

11,22,33

Click column headers to sort

Type	Species	Amino acid change	Reference
Missense	Human	D224V	33
Missense	Human	A419T	11
Missense	Human	P519T	22
Missense	Human	L601V	33

Clinically-Relevant Mutations and Pathophysiology Comments

Several inactivating mutations of the FSHR have been reported. Most, but not all, cause the mutant receptor to be retained intracellularly, thereby reducing cell surface expression [31].

Biologically Significant Variants

Type:	Single nucleotide polymorphisms
Species:	Human
Description:	Two polymorphisms in linkage disequilibrium, p.N307A and p.N680S, have been suggested to alter gonadal responsiveness to endogenous and exogenous FSH.
References:	7

General Comments
FSH can bind with high affinity to the extracellular domain of the receptor in the absence of transmembrane domains. The structure of the extracellular domain of the receptor complexed with FSH has been determined [12,18].

References

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1. Abel MH, Wootton AN, Wilkins V, Huhtaniemi I, Knight PG, Charlton HM. (2000) The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction. Endocrinology, 141 (5): 1795-803. [PMID:10803590]

2. Aharoni D, Dantes A, Oren M, Amsterdam A. (1995) cAMP-mediated signals as determinants for apoptosis in primary granulosa cells. Exp Cell Res, 218 (1): 271-82. [PMID:7537693]

3. Aittomäki K, Herva R, Stenman UH, Juntunen K, Ylöstalo P, Hovatta O, de la Chapelle A. (1996) Clinical features of primary ovarian failure caused by a point mutation in the follicle-stimulating hormone receptor gene. J Clin Endocrinol Metab, 81 (10): 3722-6. [PMID:8855829]

4. Aittomäki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehväslaiho H, Engel AR et al.. (1995) Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell, 82 (6): 959-68. [PMID:7553856]

5. Arey BJ, Deecher DC, Shen ES, Stevis PE, Meade Jr EH, Wrobel J, Frail DE, López FJ. (2002) Identification and characterization of a selective, nonpeptide follicle-stimulating hormone receptor antagonist. Endocrinology, 143 (10): 3822-9. [PMID:12239093]

6. Baccetti B, Collodel G, Costantino-Ceccarini E, Eshkol A, Gambera L, Moretti E, Strazza M, Piomboni P. (1998) Localization of human follicle-stimulating hormone in the testis. FASEB J, 12 (11): 1045-54. [PMID:9707177]

7. Behre HM, Greb RR, Mempel A, Sonntag B, Kiesel L, Kaltwasser P, Seliger E, Röpke F, Gromoll J, Nieschlag E et al.. (2005) Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation. Pharmacogenet Genomics, 15 (7): 451-6. [PMID:15970792]

8. Beubler E, Hinterleitner T, Horina G. (1990) Protein kinase C and intestinal fluid secretion: involvement of prostaglandin E2 but not of 5-hydroxytryptamine. Eur J Pharmacol, 182 (3): 543-8. [PMID:2171950]

9. Camp TA, Rahal JO, Mayo KE. (1991) Cellular localization and hormonal regulation of follicle-stimulating hormone and luteinizing hormone receptor messenger RNAs in the rat ovary. Mol Endocrinol, 5 (10): 1405-17. [PMID:1723141]

10. Dierich A, Sairam MR, Monaco L, Fimia GM, Gansmuller A, LeMeur M, Sassone-Corsi P. (1998) Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc Natl Acad Sci USA, 95 (23): 13612-7. [PMID:9811848]

11. Doherty E, Pakarinen P, Tiitinen A, Kiilavuori A, Huhtaniemi I, Forrest S, Aittomäki K. (2002) A Novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure. J Clin Endocrinol Metab, 87: 1151-1155. [PMID:11889179]

12. Fan QR, Hendrickson WA. (2005) Structure of human follicle-stimulating hormone in complex with its receptor. Nature, 433 (7023): 269-77. [PMID:15662415]

13. Flack MR, Froehlich J, Bennet AP, Anasti J, Nisula BC. (1994) Site-directed mutagenesis defines the individual roles of the glycosylation sites on follicle-stimulating hormone. J Biol Chem, 269 (19): 14015-20. [PMID:8188681]

14. Gloaguen P, Crépieux P, Heitzler D, Poupon A, Reiter E. (2011) Mapping the follicle-stimulating hormone-induced signaling networks. Front Endocrinol (Lausanne), 2: 45. [PMID:22666216]

15. Guo T, Adang AE, Dolle RE, Dong G, Fitzpatrick D, Geng P, Ho KK, Kultgen SG, Liu R, McDonald E et al.. (2004) Small molecule biaryl FSH receptor agonists. Part 1: Lead discovery via encoded combinatorial synthesis. Bioorg Med Chem Lett, 14 (7): 1713-6. [PMID:15026056]

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Contributors

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Contributors:

Sabine Costagliola
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM)
Université Libre de Bruxelles
Campus Erasme
808 Route de Lennik
Bruxelles
B-1070
Belgium

James A. Dias
Division of Molecular Medicine
Lab. of Clin.Exper. Endoc. Immunol.
Wadsworth Center
New York State Department of Health
David Axelrod Institute
120 New Scotland Avenue
Albany
N.Y.
12208
USA

Deborah L. Segaloff
Professor, Dept. Molecular Physiology and Biophysics
Professor, Dept. Obstetrics and Gynecology
University of Iowa Carver College of Medicine
Iowa City, IA 52242
USA

Axel P.N. Themmen
Department of Internal Medicine
Erasmus MC - Room Ee532
PO Box 1738
Rotterdam
3000 DR
The Netherlands

Gilbert Vassart
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM)
Université Libre de Bruxelles
Campus Erasme
808 Route de Lennik
Bruxelles
B-1070
Belgium

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