LHCGR (luteinizing hormone/choriogonadotropin receptor)

Gene

• Entrez ID: 3973
• Gene name: Luteinizing hormone/choriogonadotropin receptor
• Gene symbol: LHCGR
• Synonyms (NCBI Gene): HHG, LCGR, LGR2, LH/CG-R, LH/CGR, LHR, LHRHR, LSH-R, ULG5
• Chromosome: 2
• Chromosome location: 2p16.3
• Summary: This gene encodes the receptor for both luteinizing hormone and choriogonadotropin. This receptor belongs to the G-protein coupled receptor 1 family, and its activity is mediated by G proteins which activate adenylate cyclase. Mutations in this gene resul

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019289	hsa-miR-148b-3p	Microarray	17612493
MIRT437925	hsa-miR-513a-3p	qRT-PCR, Luciferase reporter assay	24747085
MIRT437925	hsa-miR-513a-3p	qRT-PCR, Luciferase reporter assay	24747085
MIRT437925	hsa-miR-513a-3p	qRT-PCR, Luciferase reporter assay	24747085
MIRT437925	hsa-miR-513a-3p	qRT-PCR, Luciferase reporter assay	24747085
MIRT437925	hsa-miR-513a-3p	qRT-PCR, Luciferase reporter assay	24747085
MIRT437925	hsa-miR-513a-3p	qRT-PCR, Luciferase reporter assay	24747085
MIRT1108648	hsa-miR-146a	CLIP-seq
MIRT1108649	hsa-miR-146b-5p	CLIP-seq
MIRT1108650	hsa-miR-3065-3p	CLIP-seq
MIRT1108651	hsa-miR-4461	CLIP-seq
MIRT1108652	hsa-miR-512-5p	CLIP-seq
MIRT1108653	hsa-miR-580	CLIP-seq
MIRT1108654	hsa-miR-589	CLIP-seq
MIRT1108655	hsa-miR-759	CLIP-seq
MIRT2030000	hsa-miR-3160-5p	CLIP-seq
MIRT2030001	hsa-miR-3929	CLIP-seq
MIRT2030002	hsa-miR-409-3p	CLIP-seq
MIRT2030003	hsa-miR-4419b	CLIP-seq
MIRT2030004	hsa-miR-4478	CLIP-seq
MIRT2030002	hsa-miR-409-3p	CLIP-seq
MIRT2260964	hsa-miR-548c-3p	CLIP-seq
MIRT2390115	hsa-miR-3677-5p	CLIP-seq
MIRT2390116	hsa-miR-4251	CLIP-seq
MIRT2390117	hsa-miR-4474-3p	CLIP-seq
MIRT2390118	hsa-miR-4662a-5p	CLIP-seq
MIRT2390119	hsa-miR-4775	CLIP-seq
MIRT2390120	hsa-miR-539	CLIP-seq
MIRT2390121	hsa-miR-891b	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
NR2C2	Activation	11682620
NR2F1	Repression	11682620
NR2F6	Repression	11682620

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001541	Process	Ovarian follicle development	IBA
GO:0001541	Process	Ovarian follicle development	IEA
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004964	Function	Luteinizing hormone receptor activity	IBA
GO:0004964	Function	Luteinizing hormone receptor activity	IEA
GO:0004964	Function	Luteinizing hormone receptor activity	IMP	11847099
GO:0005768	Component	Endosome	TAS	10617611
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	11847099
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	ISS
GO:0005886	Component	Plasma membrane	TAS	7719343, 10617611
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	9626653
GO:0007187	Process	G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS	7719343
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISS
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IBA
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IEA
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	ISS
GO:0007283	Process	Spermatogenesis	IEA
GO:0008528	Function	G protein-coupled peptide receptor activity	IBA
GO:0008584	Process	Male gonad development	IBA
GO:0008584	Process	Male gonad development	IEA
GO:0008584	Process	Male gonad development	TAS	7719343
GO:0008585	Process	Female gonad development	IEA
GO:0009755	Process	Hormone-mediated signaling pathway	IBA
GO:0016020	Component	Membrane	IEA
GO:0016500	Function	Protein-hormone receptor activity	IEA
GO:0022602	Process	Ovulation cycle process	IBA
GO:0022602	Process	Ovulation cycle process	IEA
GO:0030539	Process	Male genitalia development	TAS	9626653
GO:0032870	Process	Cellular response to hormone stimulus	IEA
GO:0032962	Process	Positive regulation of inositol trisphosphate biosynthetic process	IEA
GO:0032962	Process	Positive regulation of inositol trisphosphate biosynthetic process	ISS
GO:0034451	Component	Centriolar satellite	IDA
GO:0034698	Process	Response to gonadotropin	IEA
GO:0035472	Function	Choriogonadotropin hormone receptor activity	IEA
GO:0035472	Function	Choriogonadotropin hormone receptor activity	ISS
GO:0038106	Function	Choriogonadotropin hormone binding	IEA
GO:0038106	Function	Choriogonadotropin hormone binding	ISS
GO:0042700	Process	Luteinizing hormone signaling pathway	IBA
GO:0042700	Process	Luteinizing hormone signaling pathway	IMP	11847099
GO:0046544	Process	Development of secondary male sexual characteristics	IEA
GO:0050890	Process	Cognition	IMP	23227193
GO:0060065	Process	Uterus development	IEA
GO:0071371	Process	Cellular response to gonadotropin stimulus	IEA
GO:0071371	Process	Cellular response to gonadotropin stimulus	ISS
GO:0071373	Process	Cellular response to luteinizing hormone stimulus	IMP	11847099
GO:0072520	Process	Seminiferous tubule development	IEA
GO:0090030	Process	Regulation of steroid hormone biosynthetic process	IEA

Other IDs

• MIM: 152790
• HGNC: 6585
• e!Ensembl: ENSG00000138039

Protein

• UniProt ID: P22888
• Protein name: Lutropin-choriogonadotropic hormone receptor (LH/CG-R) (Luteinizing hormone receptor) (LHR) (LSH-R)
• Protein function: Receptor for lutropin-choriogonadotropic hormone (PubMed:11847099). The activity of this receptor is mediated by G proteins which activate adenylate cyclase (PubMed:11847099).
• PDB: 7FIG, 7FIH, 7FII, 7FIJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13306	LRR_5	49 → 149	BspA type Leucine rich repeat region (6 copies)	Repeat
  PF13306	LRR_5	141 → 267	BspA type Leucine rich repeat region (6 copies)	Repeat
  PF00001	7tm_1	376 → 623	7 transmembrane receptor (rhodopsin family)	Family

• Tissue specificity: TISSUE SPECIFICITY: Gonadal and thyroid cells.
• Sequence:

  MKQRFSALQLLKLLLLLQPPLPRALREALCPEPCNCVPDGALRCPGPTAGLTRLSLAYLP
  VKVIPSQAFRGLNEVIKIEISQIDSLERIEANAFDNLLNLSEILIQNTKNLRYIEPGAFI
  NLPRLKYLSICNTGIRKFPDVTKVFSSESNFILEICDNLHITTIPGNAFQGMNNESVTLK
  LYGNGFEEVQSHAFNGTTLTSLELKENVHLEKMHNGAFRGATGPKTLDISSTKLQALPSY
  GLESIQRLIATSSYSLKKLPSRETFVNLLEATLTYPSHCCAFRNLPTKEQNFSHSISENF
  SKQCESTVRKVNNKTLYSSMLAESELSGWDYEYGFCLPKTPRCAPEPDAFNPCEDIMGYD
  FLRVLIWLINILAIMGNMTVLFVLLTSRYKLTVPRFLMCNLSFADFCMGLYLLLIASVDS
  QTKGQYYNHAIDWQTGSGCSTAGFFTVFASELSVYTLTVITLERWHTITYAIHLDQKLRL
  RHAILIMLGGWLFSSLIAMLPLVGVSNYMKVSICFPMDVETTLSQVYILTILILNVVAFF
  IICACYIKIYFAVRNPELMATNKDTKIAKKMAILIFTDFTCMAPISFFAISAAFKVPLIT
  VTNSKVLLVLFYPINSCANPFLYAIFTKTFQRDFFLLLSKFGCCKRRAELYRRKDFSAYT
  SNCKNGFTGSNKPSQSTLKLSTLHCQGTALLDKTRYTEC

• Sequence length: 699

Pathways

KEGG:

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

Reactome:

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

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Disorder of sexual differentiation	Likely pathogenic; Pathogenic	rs121912524	RCV005623062	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Gonadotropin-independent familial sexual precocity	Pathogenic; Likely pathogenic	rs121912540, rs757225917, rs121912518, rs121912519, rs121912521, rs121912523, rs121912526, rs121912528, rs121912531, rs121912533, rs121912534, rs121912535, rs121912532	RCV005925362 RCV005399152 RCV000015461 RCV000015462 RCV000015467 RCV002490374 RCV000015473 RCV000015476 RCV000015483 RCV000015487 RCV000015488 RCV000015489 RCV000015493 RCV000030141	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leydig cell adenoma, somatic, with male-limited precocious puberty	Pathogenic	rs121912532	RCV000015484	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leydig cell agenesis	Pathogenic; Likely pathogenic	rs757225917, rs2529810344, rs1680042817, rs121912518, rs121912537, rs121912520, rs121912523, rs121912524, rs121912525, rs121912529, rs2104352652, rs71245621, rs121912536, rs121912538, rs121912539, rs144859947, rs773279269, rs1553387851, rs140568136, rs1572874955, rs1668121333	RCV005399152 RCV005059182 RCV003142542 RCV000763499 RCV000015464 RCV000015465 RCV000015469 RCV000015470 RCV003137526 RCV000015477 RCV000015479 RCV000015486 RCV000015490 RCV000015491 RCV000015492 RCV000581164 RCV000582170 RCV000656703 RCV000768371 RCV001027713 RCV001291522	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leydig cell hypoplasia, type II	Pathogenic	rs121912527, rs121912530	RCV000015475 RCV000015481	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leydig cell tumor	Pathogenic	rs121912532	RCV006253624	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leydig hypoplasia, type I	Likely pathogenic; Pathogenic	rs121912525	RCV000015472	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
LHCGR-related disorder	Likely pathogenic; Pathogenic	rs917607255, rs755654915, rs121912531, rs773279269	RCV003391556 RCV003408511 RCV003407338 RCV004754480	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Luteinizing hormone resistance, female	Pathogenic; Likely pathogenic	rs121912520, rs121912524, rs121912529, rs2104352652	RCV000015466 RCV000015471 RCV000015478 RCV000015480	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Precocious puberty in males	Pathogenic; Likely pathogenic	rs121912518, rs121912526	RCV000583503 RCV000581515	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pseudohermaphroditism	Pathogenic	rs750481017	RCV000583426	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
46,XY disorder of sex development	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISORDER OF SEX DEVELOPMENT, 46,XY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISORDERS OF SEX DEVELOPMENT	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL TESTOTOXICOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypergonadotropic hypogonadism	Benign; Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFERTILITY, MALE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Luteinizing hormone/choriogonadotropin receptor, lq variant	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MALE INFERTILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYSTIC OVARY SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY HYPOGONADISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TESTOTOXICOSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
46, XY Disorders of Sex Development	46, XY disorder of sex development	CTD_human_DG	19887492, 7719343		★☆☆☆☆ Found in Text Mining only
46, XY Disorders of Sex Development	46, XY disorder of sex development	BEFREE	21720050, 29912377		★☆☆☆☆ Found in Text Mining only
46,XY Disorder of Sex Development Due To LH Defects	46,XY Disorder Of Sex Development	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
46,XY Sex Reversal 3	46, XY Sex Reversal	CTD_human_DG	19887492, 7719343		★☆☆☆☆ Found in Text Mining only
Acne	Acne	HPO_DG			★☆☆☆☆ Found in Text Mining only
Acth-Independent Macronodular Adrenal Hyperplasia	Cushing`s Syndrome	BEFREE	19578593		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma, Endometrioid	Endometrial Cancer	BEFREE	22902918		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	16332935, 18971217, 26397949		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	LHGDN	16332935		★☆☆☆☆ Found in Text Mining only
Adrenal Gland Neoplasms	Adrenal neoplasia	BEFREE	19131502		★☆☆☆☆ Found in Text Mining only
Adrenocortical carcinoma	Adrenocortical carcinoma	BEFREE	18971217		★☆☆☆☆ Found in Text Mining only
Adrenocortical Carcinoma	Adrenocortical carcinoma	Pubtator	30924919	Associate	★☆☆☆☆ Found in Text Mining only
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	BEFREE	30053001		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	18439297	Associate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	18439297	Inhibit	★☆☆☆☆ Found in Text Mining only
Ambiguous Genitalia	Ambiguous Genitalia	CTD_human_DG	22615892		★☆☆☆☆ Found in Text Mining only
Amenorrhea	Amenorrhea	Pubtator	22369774, 27016457	Associate	★☆☆☆☆ Found in Text Mining only
Androgen Insensitivity Syndrome	Androgen insensitivity syndrome	Pubtator	24849377	Associate	★☆☆☆☆ Found in Text Mining only
Angiofibroma	Angiofibroma	BEFREE	23996526		★☆☆☆☆ Found in Text Mining only
Aplasia Cutis Congenita	Aplasia Cutis Congenita	BEFREE	30053001		★☆☆☆☆ Found in Text Mining only
ATAXIA-TELANGIECTASIA-LIKE DISORDER	Ataxia-Telangiectasia-Like Disorder	BEFREE	24733832		★☆☆☆☆ Found in Text Mining only
Ataxia-Telangiectasisa-Like Disorder 1	Ataxia-telangiectasia-like disorder	BEFREE	24733832		★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Azoospermia	Azoospermia	BEFREE	16730882		★☆☆☆☆ Found in Text Mining only
Azoospermia	Azoospermia	Pubtator	18508780	Associate	★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	31579974		★☆☆☆☆ Found in Text Mining only
BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS (disorder)	Blepharophimosis, ptosis, and epicanthus inversus syndrome	BEFREE	9762009		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	16464948, 17692113, 17709176, 26458823		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	17692113, 17709176, 18758818, 26458823	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms, Male	Neoplasm of male breast	LHGDN	15292356		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	18758818, 21490077	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	18971217, 21327682		★☆☆☆☆ Found in Text Mining only
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	21711548, 23951246, 33374698	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Endometrioid	Endometrioid cancer	BEFREE	22902918		★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	11063638, 20444430, 23951246, 31729966		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	BEFREE	3993676		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	3993676		★☆☆☆☆ Found in Text Mining only
Cartilage-hair hypoplasia	Cartilage-Hair Hypoplasia	BEFREE	19209621		★☆☆☆☆ Found in Text Mining only
Central Precocious Puberty	Central Precocious Puberty	BEFREE	29506309		★☆☆☆☆ Found in Text Mining only
Choroid Plexus Papilloma	Choroid Plexus Papilloma	BEFREE	29506309		★☆☆☆☆ Found in Text Mining only
Chronic kidney disease stage 5	Kidney Disease	BEFREE	9067910		★☆☆☆☆ Found in Text Mining only
Chronic Kidney Diseases	Kidney Disease	BEFREE	9067910		★☆☆☆☆ Found in Text Mining only
Congenital diaphragmatic hernia	Congenital diaphragmatic hernia	BEFREE	28295742, 31600412		★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of lung	Pulmonary hypoplasia	BEFREE	31269833		★☆☆☆☆ Found in Text Mining only
Conn Adenoma	Conn Adenoma	BEFREE	27196470		★☆☆☆☆ Found in Text Mining only
Conn Syndrome	Conn Syndrome	BEFREE	21330483		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	BEFREE	17161332		★☆☆☆☆ Found in Text Mining only
Cushing Syndrome	Cushing`s Syndrome	LHGDN	12519858		★☆☆☆☆ Found in Text Mining only
Cushing Syndrome	Cushing syndrome	Pubtator	12519858	Associate	★☆☆☆☆ Found in Text Mining only
Cushing Syndrome	Cushing`s Syndrome	BEFREE	16249277		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	31250581		★☆☆☆☆ Found in Text Mining only
Disorder of Sex Development 46 XY	46, xy disorder of sex development	Pubtator	12050206, 15719037, 18433292, 21720050, 31167162, 34338568, 39285472, 7719343	Associate	★☆☆☆☆ Found in Text Mining only
Disorders of Sex Development	Disorders of sex development	Pubtator	15719037, 18508780, 30444213, 31167162	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Down Syndrome	Down Syndrome	BEFREE	15969756		★☆☆☆☆ Found in Text Mining only
Dyslipidemias	Dyslipidemias	Pubtator	38129424	Associate	★☆☆☆☆ Found in Text Mining only
Eclampsia	Eclampsia	BEFREE	16087288		★☆☆☆☆ Found in Text Mining only
Empty follicle syndrome	Empty Follicle Syndrome	BEFREE	21683950, 29912377, 31734689		★☆☆☆☆ Found in Text Mining only
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	22902918		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	29808163	Associate	★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	BEFREE	25935136, 30965114		★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	25935136	Associate	★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	11063638, 23951246, 31729966		★☆☆☆☆ Found in Text Mining only
Erectile Dysfunction	Erectile dysfunction	Pubtator	30322327	Associate	★☆☆☆☆ Found in Text Mining only
Familial male-limited precocious puberty	Male-Limited Precocious Puberty	Orphanet			★☆☆☆☆ Found in Text Mining only
Familial Testotoxicosis	Testotoxicosis	BEFREE	10704433, 11134146, 11228053, 16087288, 16887451, 20333877, 21060208, 23861372, 26831561, 28339861, 29029242, 7527413, 7593421, 7629248, 7714085, 7892197, 8281137, 8607787, 8812739, 9661624, 9973550		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Testotoxicosis	Testotoxicosis	UNIPROT_DG	11134146, 11391350, 7629248, 7692306, 7714085, 7757065, 8281137, 8829636, 8929952, 9467560, 9661624		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Testotoxicosis	Testotoxicosis	Pubtator	11200941, 11228053, 15719037, 32757547, 35909557, 7562970, 7593421, 9973550	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Testotoxicosis	Testotoxicosis	CTD_human_DG	16684832, 18345393, 19209621, 26831561, 7692306		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Testotoxicosis	Testotoxicosis	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Testotoxicosis	Testotoxicosis	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Testotoxicosis	Testotoxicosis	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Galactosemias	Galactosemia	BEFREE	6433809		★☆☆☆☆ Found in Text Mining only
Glaucoma, Primary Open Angle	Glaucoma	BEFREE	24597656		★☆☆☆☆ Found in Text Mining only
granulosa cell tumor	Granulosa Cell Tumor	BEFREE	11063655		★☆☆☆☆ Found in Text Mining only
Graves Disease	Graves Disease	BEFREE	10524566		★☆☆☆☆ Found in Text Mining only
Gynecomastia	Gynecomastia	LHGDN	15292356		★☆☆☆☆ Found in Text Mining only
Hereditary Breast and Ovarian Cancer Syndrome	Hereditary breast and ovarian cancer syndrome	Pubtator	18758818	Associate	★☆☆☆☆ Found in Text Mining only
Hermaphroditism	Hermaphroditism	CTD_human_DG	22615892		★☆☆☆☆ Found in Text Mining only
Histiocytosis, Langerhans-Cell	Histiocytosis	BEFREE	10704433, 29305568, 7581384		★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops Fetalis	BEFREE	29304545		★☆☆☆☆ Found in Text Mining only
Hyperaldosteronism	Hyperaldosteronism	Pubtator	26397949, 27196470, 34385710	Associate	★☆☆☆☆ Found in Text Mining only
Hyperandrogenism	Hyperandrogenism	BEFREE	25586784		★☆☆☆☆ Found in Text Mining only
Hyperandrogenism	Hyperandrogenism	Pubtator	31184707	Associate	★☆☆☆☆ Found in Text Mining only
Hyperplasia	Hyperplasia	Pubtator	21490077	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	30081869		★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	LHGDN	18508780		★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	Pubtator	23884663	Associate	★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	BEFREE	17161332		★☆☆☆☆ Found in Text Mining only
Infertility	Infertility	Pubtator	18508780, 21683950, 24849377, 25935136	Associate	★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	28367994	Associate	★☆☆☆☆ Found in Text Mining only
Intersex Conditions	Disorder of sex development	CTD_human_DG	22615892		★☆☆☆☆ Found in Text Mining only
Kidney Failure, Chronic	Kidney Failure	BEFREE	9067910		★☆☆☆☆ Found in Text Mining only
Leydig Cell Adenoma, Somatic, with Male-Limited Precocious Puberty	Somatic Leydig Cell Adenoma With Male-Limited Precocious Puberty	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leydig cell agenesis	Leydig Cell Agenesis	BEFREE	10704433, 11299516, 11857565, 15607529, 16433250, 19551906, 25079470, 26246498, 26554443, 29305568, 7581384, 8843415		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leydig cell agenesis	Leydig Cell Agenesis	UNIPROT_DG	12050206, 15372531, 15472221, 19551906, 7719343, 8559204, 9215288, 9514160, 9626144, 9626653		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leydig cell agenesis	Leydig Cell Agenesis	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leydig cell agenesis	Leydig Cell Agenesis	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leydig cell agenesis	Leydig Cell Agenesis	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leydig cell hypoplasia due to complete LH resistance	Leydig Cell Hypoplasia	Orphanet			★☆☆☆☆ Found in Text Mining only
Leydig cell hypoplasia due to partial LH resistance	Leydig Cell Hypoplasia	Orphanet			★☆☆☆☆ Found in Text Mining only
Leydig Cell Tumor	Leydig Cell Tumor	CTD_human_DG	10580072, 11857565		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leydig Cell Tumor	Leydig Cell Tumor	BEFREE	11056247, 11857565, 22727875		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leydig Cell Tumor	Leydig Cell Tumor	UNIPROT_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Luteinizing Hormone Resistance, Female	Luteinizing Hormone Resistance, Female	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Luteinizing Hormone Resistance, Female	Luteinizing Hormone Resistance, Female	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Macular Degeneration	Macular degeneration	Pubtator	28775256	Associate	★☆☆☆☆ Found in Text Mining only
Male Pseudohermaphroditism	Male Pseudohermaphroditism	BEFREE	10704433, 10714363, 16433250, 19551906, 7719343		★☆☆☆☆ Found in Text Mining only
Male Pseudohermaphroditism	Male Pseudohermaphroditism	CTD_human_DG	19887492, 7719343		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	16464948, 17692113, 17709176, 26458823		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	11063638, 20444430, 21327682, 28427435		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	25393079		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of testis	Malignant Neoplasm Of Testis	BEFREE	22882535		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	10704433		★☆☆☆☆ Found in Text Mining only
Malignant Testicular Germ Cell Tumor	Malignant testicular germ cell tumor	BEFREE	22245602, 22882535		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	12679452		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	11063638, 11857565, 12150333, 17337116, 17363137, 18971217, 21327682, 23951246, 8807640		★☆☆☆☆ Found in Text Mining only
Nephroblastoma	Nephroblastoma	BEFREE	25434310		★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Primary ovarian failure	Ovarian Failure	Orphanet			★☆☆☆☆ Found in Text Mining only
Oestrogen receptor positive breast cancer	Oestrogen Receptor Positive Breast Cancer	BEFREE	26458823		★☆☆☆☆ Found in Text Mining only
Oligospermia	Oligospermia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ovarian Diseases	Ovarian diseases	Pubtator	22355044	Stimulate	★☆☆☆☆ Found in Text Mining only
Ovarian Diseases	Ovarian diseases	Pubtator	38297261	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Dysgenesis 2	Ovarian dysgenesis	Pubtator	25565299	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Hyperstimulation Syndrome	Ovarian Hyperstimulation Syndrome	BEFREE	17074323, 23883350, 31115963		★☆☆☆☆ Found in Text Mining only
Ovarian Hyperstimulation Syndrome	Ovarian hyperstimulation syndrome	Pubtator	23883350, 25888426	Associate	★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	11063638, 20444430		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	LHGDN	19010824		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	19010824, 21711548, 21765906, 22214378, 24554412, 25528498, 28427435, 31729966, 33374698	Associate	★☆☆☆☆ Found in Text Mining only
Paroxysmal ventricular fibrillation	Paroxysmal ventricular fibrillation	Pubtator	22369774	Associate	★☆☆☆☆ Found in Text Mining only
Penile hypospadias	Penile Hypospadias	BEFREE	17161332		★☆☆☆☆ Found in Text Mining only
Pheochromocytoma	Pheochromocytoma	Pubtator	35189708	Associate	★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	10704433, 11238527, 22180642, 22356187, 22546001, 22902918, 23208300, 24592983, 25649397, 25978310, 26305227, 26474478, 26662070, 28068351, 30182769, 31276164, 31735954		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	GWASDB_DG	21151128, 22885925		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	GWASCAT_DG	21151128, 22885925		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	22546001, 23118426, 24592983, 25565299, 25649397, 25978310, 26305227, 26474478, 26662070, 28068351, 30844144, 31184707, 35872929, 36585675, 38129424	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	31276164	Stimulate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	38008503	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Precocious Puberty	Precocious puberty	BEFREE	10704433, 11288780, 11936470, 16887451, 19209621, 29029242, 7527413, 7692306, 7757065, 8072545, 8812739, 9255219, 9661624		★☆☆☆☆ Found in Text Mining only
Precocious Puberty	Precocious puberty	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary hypogonadism	Hypogonadism	BEFREE	28591755, 29363275		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary hypogonadism	Hypogonadism	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary physiologic amenorrhea	Physiologic Amenorrhea	BEFREE	10704433		★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Primary pigmented nodular adrenocortical disease	Pigmented Nodular Adrenocortical Disease	BEFREE	19578593		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	25393079		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	32881970	Associate	★☆☆☆☆ Found in Text Mining only
Pseudohermaphroditism	Pseudohermaphroditism	CTD_human_DG	22615892		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pseudohermaphroditism	Pseudohermaphroditism	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Respiratory Distress Syndrome, Adult	Respiratory Distress Syndrome	BEFREE	29609546		★☆☆☆☆ Found in Text Mining only
Secondary physiologic amenorrhea	Secondary Physiologic Amenorrhea	BEFREE	25774885		★☆☆☆☆ Found in Text Mining only
Seminoma	Seminoma	BEFREE	22245602		★☆☆☆☆ Found in Text Mining only
Sex Differentiation Disorders	Sex Differentiation Disorders	CTD_human_DG	22615892		★☆☆☆☆ Found in Text Mining only
Sexual Dysfunction	Sexual Dysfunction	BEFREE	28339861		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 2	Spinocerebellar Ataxia	BEFREE	19473475		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	31807530		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	32034058	Associate	★☆☆☆☆ Found in Text Mining only
Subfertility	Subfertility	BEFREE	16730882		★☆☆☆☆ Found in Text Mining only
Testicular hypogonadism	Testicular Hypogonadism	BEFREE	10704433		★☆☆☆☆ Found in Text Mining only
Testicular Neoplasms	Testicular Neoplasms	BEFREE	10704433		★☆☆☆☆ Found in Text Mining only
Testotoxicosis	Testotoxicosis	BEFREE	11857565, 16087288, 16759041, 16887451, 19492585, 20333877, 29029242, 29538680, 7527413, 7714085, 8607787, 8812739		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Testotoxicosis	Testotoxicosis	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid Gland Follicular Adenoma	Thyroid Gland Follicular Adenoma	BEFREE	25586784		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	21483740	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Fibrillation, Paroxysmal Familial, 1	Ventricular Fibrillation	BEFREE	24874553		★☆☆☆☆ Found in Text Mining only