LHCGR

Protein identityUniProt · HPA

UniProt accession

P22888

Gene

LHCGR

Ensembl

ENSG00000138039

Chromosome

2

Canonical length

699 aa

Protein class

Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Plasma membrane,Centriolar satellite

OverviewNCBI Gene

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 result in disorders of male secondary sexual character development, including familial male precocious puberty, also known as testotoxicosis, hypogonadotropic hypogonadism, Leydig cell adenoma with precocious puberty, and male pseudohermaphtoditism with Leydig cell hypoplasia. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

699 residues, UniProt reviewed canonical sequence.

>P22888|LHCGR
     1  MKQRFSALQL LKLLLLLQPP LPRALREALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP
    61  VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLNL SEILIQNTKN LRYIEPGAFI
   121  NLPRLKYLSI CNTGIRKFPD VTKVFSSESN FILEICDNLH ITTIPGNAFQ GMNNESVTLK
   181  LYGNGFEEVQ SHAFNGTTLT SLELKENVHL EKMHNGAFRG ATGPKTLDIS STKLQALPSY
   241  GLESIQRLIA TSSYSLKKLP SRETFVNLLE ATLTYPSHCC AFRNLPTKEQ NFSHSISENF
   301  SKQCESTVRK VNNKTLYSSM LAESELSGWD YEYGFCLPKT PRCAPEPDAF NPCEDIMGYD
   361  FLRVLIWLIN ILAIMGNMTV LFVLLTSRYK LTVPRFLMCN LSFADFCMGL YLLLIASVDS
   421  QTKGQYYNHA IDWQTGSGCS TAGFFTVFAS ELSVYTLTVI TLERWHTITY AIHLDQKLRL
   481  RHAILIMLGG WLFSSLIAML PLVGVSNYMK VSICFPMDVE TTLSQVYILT ILILNVVAFF
   541  IICACYIKIY FAVRNPELMA TNKDTKIAKK MAILIFTDFT CMAPISFFAI SAAFKVPLIT
   601  VTNSKVLLVL FYPINSCANP FLYAIFTKTF QRDFFLLLSK FGCCKRRAEL YRRKDFSAYT
   661  SNCKNGFTGS NKPSQSTLKL STLHCQGTAL LDKTRYTEC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LHCGR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

2.1 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LHCGR.

Disease | AllUniProt

Conditions LHCGR is implicated in, by any mechanism.

• Familial male precocious puberty (FMPP) MIM:176410
• Luteinizing hormone resistance (LHR) MIM:238320

Disease | GeneticClinVar

55 pathogenic / likely-pathogenic of 317 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Leydig cell agenesis
• Gonadotropin-independent familial sexual precocity
• Luteinizing hormone resistance, female
• LHCGR-related disorder
• Leydig cell hypoplasia, type II

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.89

gnomAD pLI

0

gnomAD missense Z

0.16

DepMap mean gene effect

0.08

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• cellular response to gonadotropin stimulus
• cellular response to luteinizing hormone stimulus
• cognition
• development of secondary male sexual characteristics
• G protein-coupled receptor signaling pathway
• G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• hormone-mediated signaling pathway
• luteinizing hormone signaling pathway
• male genitalia development
• male gonad development
• ovarian follicle development
• ovulation cycle process
• phospholipase C-activating G protein-coupled receptor signaling pathway
• positive regulation of inositol trisphosphate biosynthetic process
• seminiferous tubule development
• spermatogenesis
• uterus development
• regulation of steroid hormone biosynthetic process

Molecular functions

• G protein-coupled peptide receptor activity
• choriogonadotropin hormone binding
• choriogonadotropin hormone receptor activity
• luteinizing hormone receptor activity

Cellular components

• centriolar satellite
• endosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Glycoprotein hormone receptor family
• GPCR, rhodopsin-like, 7TM
• BspA-type LRR region
• Leucine-rich repeat domain superfamily
• 7 transmembrane receptor (rhodopsin family)
• BspA type Leucine rich repeat region (6 copies)
• Lutropin-choriogonadotropic hormone receptor

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Leucine-rich repeat
• Lipoprotein
• Membrane
• Palmitate
• Receptor
• Repeat
• Signal
• Sulfation
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of LHCGR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARRB1
• COPS5