FSHR (follicle stimulating hormone receptor)

Gene

• Entrez ID: 2492
• Gene name: Follicle stimulating hormone receptor
• Gene symbol: FSHR
• Synonyms: FSHR1, FSHRO, LGR1, ODG1
• Chromosome: 2
• Chromosome location: 2p16.3
• Summary: The protein encoded by this gene belongs to family 1 of G-protein coupled receptors. It is the receptor for follicle stimulating hormone and functions in gonad development. Mutations in this gene cause ovarian dysgenesis type 1, and also ovarian hyperstim

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs6165	C>A,G,T	Drug-response, benign	Coding sequence variant, missense variant, genic downstream transcript variant
rs28928870	G>A,T	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs28928871	C>T	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs121909658	G>A	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs121909659	A>G,T	Likely-pathogenic, pathogenic	Intron variant, 5 prime UTR variant, coding sequence variant, missense variant
rs121909660	G>A	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs121909661	C>T	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs121909662	G>A,T	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs121909663	T>C	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs121909664	A>G,T	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs121909665	G>T	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs386833510	G>C	Likely-pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs386833511	G>A	Likely-pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs386833512	G>T	Pathogenic-likely-pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs386833513	G>C	Likely-pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs386833514	A>C	Likely-pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs386833515	T>A,C	Likely-pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs955385021	A>G	Pathogenic	5 prime UTR variant, initiator codon variant, missense variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT440611	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT440611	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT1005489	hsa-miR-3200-5p	CLIP-seq
MIRT1005490	hsa-miR-4504	CLIP-seq
MIRT1005491	hsa-miR-4539	CLIP-seq
MIRT1005492	hsa-miR-542-3p	CLIP-seq
MIRT1005493	hsa-miR-758	CLIP-seq
MIRT2231551	hsa-miR-31	CLIP-seq
MIRT2231552	hsa-miR-4499	CLIP-seq
MIRT2231553	hsa-miR-4680-3p	CLIP-seq
MIRT2231554	hsa-miR-4696	CLIP-seq
MIRT2231555	hsa-miR-548an	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
E2F1	Unknown	11883315
E2F5	Unknown	11883315
MTA2	Repression	23086931
NR5A1	Unknown	11328853

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004963	Function	Follicle-stimulating hormone receptor activity	IBA	21873635
GO:0004963	Function	Follicle-stimulating hormone receptor activity	IDA	24692546
GO:0004963	Function	Follicle-stimulating hormone receptor activity	IMP	11847099
GO:0005515	Function	Protein binding	IPI	15196694, 17030088, 20600589
GO:0005886	Component	Plasma membrane	IDA	11847099
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0007186	Process	G protein-coupled receptor signaling pathway	IDA	24692546
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA	21873635
GO:0007190	Process	Activation of adenylate cyclase activity	IBA	21873635
GO:0007283	Process	Spermatogenesis	TAS	9020851
GO:0007292	Process	Female gamete generation	TAS	9020851
GO:0008406	Process	Gonad development	TAS	9020851
GO:0008528	Function	G protein-coupled peptide receptor activity	IBA	21873635
GO:0008584	Process	Male gonad development	IBA	21873635
GO:0008584	Process	Male gonad development	IEP	17848411
GO:0008585	Process	Female gonad development	TAS	7553856
GO:0009755	Process	Hormone-mediated signaling pathway	IBA	21873635
GO:0010738	Process	Regulation of protein kinase A signaling	IMP	24058690
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	IMP	24058690
GO:0016021	Component	Integral component of membrane	IDA	24692546
GO:0042699	Process	Follicle-stimulating hormone signaling pathway	IBA	21873635
GO:0042699	Process	Follicle-stimulating hormone signaling pathway	IDA	24692546
GO:0042699	Process	Follicle-stimulating hormone signaling pathway	IMP	11847099
GO:0043235	Component	Receptor complex	IDA	24692546
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IDA	24058690
GO:0071372	Process	Cellular response to follicle-stimulating hormone stimulus	IMP	11847099

Other IDs

• MIM: 136435
• HGNC: 3969
• e!Ensembl: ENSG00000170820

Protein

• UniProt ID: P23945
• Protein name: Follicle-stimulating hormone receptor (FSH-R) (Follitropin receptor)
• Protein function: G protein-coupled receptor for follitropin, the follicle-stimulating hormone (PubMed:11847099, PubMed:24058690, PubMed:24692546). Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways (PubMed:24058690). {ECO:
• PDB: 1XWD, 4AY9, 4MQW, 8I2G, 8I2H
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01462	LRRNT	17 → 45	Leucine rich repeat N-terminal domain	Family
  PF13306	LRR_5	46 → 147	BspA type Leucine rich repeat region (6 copies)	Repeat
  PF13306	LRR_5	139 → 257	BspA type Leucine rich repeat region (6 copies)	Repeat
  PF12369	GnHR_trans	282 → 349	Gonadotropin hormone receptor transmembrane region	Family
  PF00001	7tm_1	379 → 626	7 transmembrane receptor (rhodopsin family)	Family

• Sequence:

  MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRV
  IQKGAFSGFGDLEKIEISQNDVLEVIEADVFSNLPKLHEIRIEKANNLLYINPEAFQNLP
  NLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVILWLNKN
  GIQEIHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILDISRTRIHSLPSYGLEN
  LKKLRARSTYNLKKLPTLEKLVALMEASLTYPSHCCAFANWRRQISELHPICNKSILRQE
  VDYMTQARGQRSSLAEDNESSYSRGFDMTYTEFDYDLCNEVVDVTCSPKPDAFNPCEDIM
  GYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLCIGIYLLLIAS
  VDIHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERWHTITHAMQLDCK
  VQLRHAASVMVMGWIFAFAAALFPIFGISSYMKVSICLPMDIDSPLSQLYVMSLLVLNVL
  AFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLCMAPISFFAISASLKVP
  LITVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSKCGCYEMQAQIYRTETSS
  TVHNTHPRNGHCSSAPRVTNGSTYILVPLSHLAQN

• Sequence length: 695

Pathways

KEGG:

cAMP signaling pathway
Neuroactive ligand-receptor interaction
Hormone signaling
Ovarian steroidogenesis

Reactome:

Hormone ligand-binding receptors
G alpha (s) signalling events
ADORA2B mediated anti-inflammatory cytokines production

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Microcephaly	Microcephaly	rs397704721, rs267607176, rs267607177, rs397704725, rs267606717, rs267606718, rs199422202, rs121434311, rs199422203, rs199422126, rs387906274, rs121434305, rs199422125, rs199422135, rs189678019, rs199422184, rs137852994, rs137852995, rs137852996, rs137852997, rs145489194, rs80338860, rs137852494, rs121918609, rs199422207, rs199422206, rs29001566, rs864321658, rs199422138, rs199422139, rs199422141, rs199422144, rs199422147, rs199422151, rs199422152, rs199422153, rs199422157, rs199422159, rs199422160, rs199422161, rs140602858, rs199422164, rs199422165, rs148294838, rs199422134, rs199422168, rs199422172, rs199422173, rs199422131, rs199422177, rs199422180, rs199422185, rs199422186, rs199422187, rs143931757, rs199422189, rs199422192, rs199422194, rs199422195, rs199422196, rs199422197, rs199422199, rs753597039, rs1488084787, rs387906961, rs755862917, rs387907082, rs587776899, rs387907083, rs587776900, rs587776901, rs387907084, rs863223322, rs764201220, rs202247811, rs763915472, rs587776986, rs587777036, rs398122971, rs374351172, rs373278668, rs398122976, rs121909123, rs587783393, rs730882076, rs587783211, rs144716013, rs606231255, rs587783215, rs587783216, rs587783220, rs587783221, rs587783225, rs587783227, rs587783228, rs587783230, rs587783238, rs587783239, rs587783240, rs587783245, rs587783247, rs587783248, rs587783258, rs587783259, rs587783263, rs587783265, rs587783268, rs587783269, rs587783272, rs587783275, rs587783277, rs587783278, rs587783280, rs587783282, rs587783283, rs587783285, rs587783287, rs587783288, rs587783289, rs587783292, rs587783295, rs587784452, rs587783741, rs587783735, rs587783392, rs587783390, rs587783387, rs587783410, rs202058504, rs587783423, rs587783421, rs587783414, rs587784553, rs587784558, rs587784546, rs587784549, rs587784554, rs587784412, rs876661307, rs869025200, rs747831095, rs748529285, rs797045316, rs797045315, rs797045314, rs759632528, rs797045313, rs797045311, rs754282058, rs797045441, rs797045454, rs797045430, rs869312853, rs797046109, rs767399782, rs863225127, rs863225464, rs863225465, rs780270096, rs864321621, rs864321620, rs775277800, rs879253817, rs869312824, rs761447719, rs753406334, rs147622433, rs199422137, rs879255522, rs879255524, rs879255523, rs886037892, rs886037893, rs886037894, rs886037895, rs199422169, rs886041709, rs886041282, rs138228629, rs759188041, rs769688376, rs1057517688, rs1057519087, rs1057518268, rs933106143, rs201362977, rs754909135, rs1057520873, rs1060499758, rs1060499757, rs199422146, rs748016594, rs1085307120, rs763715733, rs1064795945, rs763800571, rs1554728351, rs1553227021, rs555866170, rs1553895368, rs1334947797, rs769818500, rs1321892596, rs1553227645, rs1404276011, rs1553228275, rs1554471681, rs1554496609, rs1555420891, rs1555418825, rs587784548, rs1555723585, rs199736219, rs745997770, rs765275884, rs1553924800, rs1554730137, rs1229568621, rs1482100822, rs979186313, rs758157294, rs1555294652, rs1555299107, rs1553264033, rs1553259539, rs1553254322, rs1553259528, rs981349334, rs1553264036, rs1553253022, rs754267846, rs776034810, rs1342429887, rs752140135, rs1006898944, rs571640983, rs1477524771, rs763909256, rs199910503, rs1553223496, rs759663956, rs1553446603, rs1555139372, rs1555143325, rs1350194762, rs1555141158, rs1553225179, rs769481947, rs769364943, rs748011724, rs1334301723, rs746341112, rs149225624, rs765113367, rs1567024512, rs142865061, rs772050241, rs201721894, rs1557966012, rs1379578836, rs1568334868, rs1185537869, rs1602333390, rs1163303148, rs774338373, rs770540184, rs1571600045, rs1571601267, rs1571602991, rs1588472215, rs1599841026, rs1558328287, rs1571600860, rs1571596976, rs1309880692, rs1435239428, rs1588634016, rs1751797979, rs1810830776, rs1815354949, rs1949984655, rs886039658, rs1943461045, rs777711720, rs2031759596, rs1555710223, rs1221031683, rs774069989, rs2058919680, rs1170413397, rs1213710245, rs1599851667, rs1599760058, rs1971033478, rs746967357
Osteoporosis	Osteoporosis	rs72658152, rs72667023, rs587776916, rs72656370, rs768615287
Ovarian hyperstimulation syndrome	Ovarian Hyperstimulation Syndrome, Ovarian Hyperstimulation Syndrome, Familial Gestational Spontaneous	rs28928870, rs28928871, rs121909663, rs121909664, rs121909665	12930928, 19573286, 12930927, 17721928, 25581598, 16278261, 24058690, 15080154, 18248882
Prostate cancer	Prostate carcinoma	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	20932654
Pulmonary fibrosis	Pulmonary Fibrosis	rs121918666, rs199422300, rs121917737, rs121917834, rs199422294, rs201159197, rs199422297, rs199422305, rs751381953, rs876661305, rs878853260, rs863223336, rs786205702, rs1555811762, rs1060502990, rs1555903332, rs1554038539, rs1554042899, rs938938578

Unknown
Disease name	Disease term	dbSNP ID	References
46, xx gonadal dysgenesis	46,XX gonadal dysgenesis
46,xx gonadal dysgenesis	Pure Gonadal Dysgenesis, 46, XX		7553856, 11889179, 12571157
Arachnodactyly	Arachnodactyly
Dwarfism	Dwarfism
Enlarged polycystic ovaries	Enlarged polycystic ovaries
Erectile dysfunction	Erectile dysfunction		20932654
Gonadal dysgenesis	Gonadal Dysgenesis, Gonadal Dysgenesis, 46,XX		12915623, 7553856, 9851774, 11889179, 10551778, 9769327, 12571157
Osteopenia	Osteopenia
Osteoporosis of vertebrae	Osteoporosis of vertebrae
Sclerocystic ovaries	Sclerocystic Ovaries		22885925
Physiologic amenorrhea	Primary physiologic amenorrhea
Pleural effusion	Pleural effusion disorder
Polycystic ovary syndrome	Polycystic Ovary Syndrome		22885925
Premature menopause	Premature Menopause
Ovarian failure	NON RARE IN EUROPE: Primary ovarian failure
Secondary physiologic amenorrhea	Secondary physiologic amenorrhea
Streak ovary	Streak ovary
Urogenital abnormalities	Urogenital Abnormalities