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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
LHCGR
luteinizing hormone/choriogonadotropin receptor
Chromosome 2 Β· 2p16.3
NCBI Gene: 3973Ensembl: ENSG00000138039.16HGNC: HGNC:6585UniProt: P22888
260PubMed Papers
22Diseases
5Drugs
55Pathogenic Variants
FUNCTIONAL ROLE
Receptor
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cellular response to luteinizing hormone stimulusplasma membranecognitionluteinizing hormone signaling pathwayLeydig cell hypoplasia, type 1familial male-limited precocious pubertyinfertilityfemale infertility
✦AI Summary

LHCGR encodes the luteinizing hormone/choriogonadotropin receptor, a G-protein coupled receptor that binds both luteinizing hormone (LH) and human chorionic gonadotropin (hCG) 1. The receptor mediates its activity through G proteins that activate adenylyl cyclase signaling pathways 2. LHCGR activation follows a distinctive 'push-and-pull' mechanism where hormone binding pushes the extracellular domain upward while a conserved 10-residue fragment (P10) from the hinge loop acts as a tethered agonist to induce transmembrane domain conformational changes 1. The receptor plays essential roles in reproductive physiology, including ovarian follicle development, steroidogenesis, and corpus luteum maintenance 34. LHCGR expression is regulated by transcription factors including SP1 and shows positive feedback regulation by hCG 4. Inactivating mutations cause a spectrum of disorders from Leydig cell hypoplasia and ambiguous genitalia in males to primary amenorrhea and infertility in females 2. The receptor has been implicated in polycystic ovary syndrome pathogenesis 5 and primary ovarian insufficiency 6. Beyond reproductive tissues, aberrant LHCGR expression occurs in various endocrine tumors including adrenal adenomas and pheochromocytomas 7.

Sources cited
1
LHCGR binds both LH and hCG, and uses a 'push-and-pull' activation mechanism with P10 fragment as tethered agonist
PMID: 34552239
2
Receptor activates G proteins and adenylyl cyclase; mutations cause reproductive disorders
PMID: 23392092
3
LHCGR plays roles in ovarian follicle development and maturation
PMID: 40663384
4
LHCGR is regulated by SP1 transcription factor and shows positive feedback by hCG in luteal cells
PMID: 30954507
5
LHCGR is implicated in polycystic ovary syndrome pathogenesis
PMID: 34161185
6
LHCGR mutations are associated with primary ovarian insufficiency
PMID: 34794894
7
Aberrant LHCGR expression occurs in various endocrine tumors
PMID: 39326429
Disease Associationsβ“˜22
Leydig cell hypoplasia, type 1Open Targets
0.78Strong
familial male-limited precocious pubertyOpen Targets
0.74Strong
infertilityOpen Targets
0.56Moderate
female infertilityOpen Targets
0.56Moderate
peripheral precocious pubertyOpen Targets
0.56Moderate
Leydig cell hypoplasiaOpen Targets
0.49Moderate
Precocious puberty in malesOpen Targets
0.49Moderate
Abnormality of the skeletal systemOpen Targets
0.49Moderate
primary ovarian insufficiencyOpen Targets
0.48Moderate
anovulationOpen Targets
0.46Moderate
obesityOpen Targets
0.45Moderate
disorder of sexual differentiationOpen Targets
0.43Moderate
Genetic 46,XY disorder of sex developmentOpen Targets
0.43Moderate
polycystic ovary syndromeOpen Targets
0.39Weak
hypogonadismOpen Targets
0.39Weak
Leydig cell hypoplasia due to complete LH resistanceOpen Targets
0.37Weak
Leydig cell hypoplasia due to partial LH resistanceOpen Targets
0.37Weak
positive regulation of ovulationOpen Targets
0.37Weak
pseudohermaphroditismOpen Targets
0.33Weak
smoking initiationOpen Targets
0.33Weak
Familial male precocious pubertyUniProt
Luteinizing hormone resistanceUniProt
Pathogenic Variants55
NM_000233.4(LHCGR):c.1691A>G (p.Asp564Gly)Pathogenic
Gonadotropin-independent familial sexual precocity|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 564
NM_000233.4(LHCGR):c.1733A>G (p.Asp578Gly)Pathogenic
Gonadotropin-independent familial sexual precocity|Precocious puberty in males|not provided|Gonadotropin-independent familial sexual precocity;Leydig cell agenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 578
NM_000233.4(LHCGR):c.1847C>A (p.Ser616Tyr)Pathogenic
Leydig hypoplasia, type I|not provided|Leydig cell agenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 616
NM_000233.4(LHCGR):c.1691A>T (p.Asp564Val)Pathogenic
not provided|Gonadotropin-independent familial sexual precocity
β˜…β˜…β˜†β˜†2025β†’ Residue 564
NM_000233.4(LHCGR):c.562G>T (p.Glu188Ter)Pathogenic
not provided|Leydig cell agenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 188
NM_000233.4(LHCGR):c.370C>T (p.Arg124Ter)Pathogenic
Leydig cell agenesis|not provided|LHCGR-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 124
NM_000233.4(LHCGR):c.1624A>C (p.Ile542Leu)Pathogenic
Gonadotropin-independent familial sexual precocity|not provided|LHCGR-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 542
NM_000233.4(LHCGR):c.1635C>A (p.Cys545Ter)Pathogenic
Leydig cell agenesis|Gonadotropin-independent familial sexual precocity;Leydig cell agenesis|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 545
NM_000233.4(LHCGR):c.1660C>T (p.Arg554Ter)Pathogenic
Leydig cell agenesis|Luteinizing hormone resistance, female|not provided|See cases|Disorder of sexual differentiation
β˜…β˜…β˜†β˜†2023β†’ Residue 554
NM_000233.4(LHCGR):c.1435C>T (p.Arg479Ter)Pathogenic
not provided|Gonadotropin-independent familial sexual precocity;Leydig cell agenesis
β˜…β˜…β˜†β˜†2023β†’ Residue 479
NM_000233.4(LHCGR):c.384-2A>GPathogenic
Leydig cell agenesis
β˜…β˜†β˜†β˜†2026
NM_000233.4(LHCGR):c.1118C>T (p.Ala373Val)Likely pathogenic
Gonadotropin-independent familial sexual precocity
β˜…β˜†β˜†β˜†2025β†’ Residue 373
NM_000233.4(LHCGR):c.947+1G>CPathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_000233.4(LHCGR):c.1060G>A (p.Glu354Lys)Pathogenic
Leydig cell agenesis|Luteinizing hormone resistance, female
β˜…β˜†β˜†β˜†2024β†’ Residue 354
NM_000233.4(LHCGR):c.1111_1112dup (p.Leu372fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 372
NM_000233.4(LHCGR):c.220G>T (p.Glu74Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 74
NM_000233.4(LHCGR):c.866+1G>CLikely pathogenic
Gonadotropin-independent familial sexual precocity;Leydig cell agenesis
β˜…β˜†β˜†β˜†2024
NM_000233.4(LHCGR):c.1193T>C (p.Met398Thr)Likely pathogenic
Gonadotropin-independent familial sexual precocity|Precocious puberty in males
β˜…β˜†β˜†β˜†2024β†’ Residue 398
NM_000233.4(LHCGR):c.1786del (p.Val596fs)Likely pathogenic
Gonadotropin-independent familial sexual precocity;Leydig cell agenesis
β˜…β˜†β˜†β˜†2024β†’ Residue 596
NM_000233.4(LHCGR):c.1732G>A (p.Asp578Asn)Likely pathogenic
Gonadotropin-independent familial sexual precocity;Leydig cell agenesis
β˜…β˜†β˜†β˜†2024β†’ Residue 578
View on ClinVar β†—
Drug Targets5
CHORIOGONADOTROPIN ALFAApproved
Luteinizing hormone/Choriogonadotropin receptor agonist
anovulation
GONADOTROPIN, CHORIONICApproved
Luteinizing hormone/Choriogonadotropin receptor agonist
LH (MENOTROPINS)Phase III
Luteinizing hormone/Choriogonadotropin receptor agonist
infertility
LUTROPIN ALFAApproved
Luteinizing hormone/Choriogonadotropin receptor agonist
female infertility
MENOTROPINSApproved
Follicle stimulating hormone receptor agonist
female infertility
Related Genes
GPHB5Protein interaction100%HSD3B2Protein interaction99%CGB5Protein interaction97%CGAProtein interaction95%TSHBProtein interaction95%GNASProtein interaction93%
Tissue Expression6 tissues
Ovary
100%
Lung
3%
Bone Marrow
1%
Heart
0%
Liver
0%
Brain
0%
Gene Interaction Network
Click a node to explore
LHCGRGPHB5HSD3B2CGB5CGATSHBGNAS
PROTEIN STRUCTURE
Preparing viewer…
PDB7FIH Β· 3.20 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.06LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.81 [0.62–1.06]
RankingsWhere LHCGR stands among ~20K protein-coding genes
  • #1,459of 20,598
    Most Researched260 Β· top 10%
  • #385of 1,025
    FDA-Approved Drug Targets4
  • #1,239of 5,498
    Most Pathogenic Variants55 Β· top quartile
  • #10,588of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedLHCGR
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Autophagy in ovary and polycystic ovary syndrome: role, dispute and future perspective.
PMID: 34161185
Autophagy Β· 2021
1.00
2
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
0.90
3
Hormone- and antibody-mediated activation of the thyrotropin receptor.
PMID: 35940204
Nature Β· 2022
0.80
4
Gene expression pattern predictive of human ovarian follicle development and maturation.
PMID: 40663384
Reproduction Β· 2025
0.70
5
Precise Correction of Lhcgr Mutation in Stem Leydig Cells by Prime Editing Rescues Hereditary Primary Hypogonadism in Mice.
PMID: 37697644
Adv Sci (Weinh) Β· 2023
0.60