Human Gene LHCGR (uc002rwu.4) Description and Page Index
  Description: Homo sapiens luteinizing hormone/choriogonadotropin receptor (LHCGR), mRNA.
RefSeq Summary (NM_000233): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The extent of this transcript is supported by transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: M63108.1, S57793.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA2148874, SAMEA2149178 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000294954.12/ ENSP00000294954.6 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr2:48,913,913-48,982,880 Size: 68,968 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg19 chr2:48,914,836-48,982,810 Size: 67,975 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:48,913,913-48,982,880)mRNA (may differ from genome)Protein (699 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKB

-  Comments and Description Text from UniProtKB
  ID: LSHR_HUMAN
DESCRIPTION: RecName: Full=Lutropin-choriogonadotropic hormone receptor; Short=LH/CG-R; AltName: Full=Luteinizing hormone receptor; Short=LHR; Short=LSH-R; Flags: Precursor;
FUNCTION: Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
TISSUE SPECIFICITY: Gonadal and thyroid cells.
DISEASE: Defects in LHCGR are a cause of familial male precocious puberty (FMPP) [MIM:176410]; also known as testotoxicosis. In FMPP the receptor is constitutively activated.
DISEASE: Defects in LHCGR are the cause of luteinizing hormone resistance (LHR) [MIM:238320]; also known as Leydig cell hypoplasia in males. LHR is an autosomal recessive disorder characterized by unresponsiveness to luteinizing hormone, defective sexual development in males, and defective follicular development and ovulation, amenorrhea and infertility in females. Two forms of the disorder have been defined in males. Type 1 is a severe form characterized by complete 46,XY male pseudohermaphroditism, low testosterone and high luteinizing hormone levels, total lack of responsiveness to luteinizing and chorionic gonadotropin hormones, lack of breast development, and absent development of secondary male sex characteristics. Type 2, a milder form, displays a broader range of phenotypic expression ranging from micropenis to severe hypospadias.
SIMILARITY: Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.
SIMILARITY: Contains 6 LRR (leucine-rich) repeats.
SIMILARITY: Contains 1 LRRNT domain.
WEB RESOURCE: Name=GRIS; Note=Glycoprotein-hormone Receptors Information System; URL="http://gris.ulb.ac.be/";
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/LHRID288.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LHCGR";
WEB RESOURCE: Name=Sequence-structure-function-analysis of glycoprotein hormone receptors; URL="http://www.ssfa-gphr.de/";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): LHCGR
CDC HuGE Published Literature: LHCGR
Positive Disease Associations: Body Weight , Body Weights and Measures , breast cancer , Erythrocyte Count , familial male-limited precocious puberty. , Menarch|Obesity|POF - Premature ovarian failure|POLYCYSTIC OVARIAN SYNDROME|Polycystic Ovary Syndrome|Primary Ovarian Insufficiency|Puberty, Delayed|Puberty, Precocious , Polycystic Ovary Syndrome , Response to radiation , Stroke
Related Studies:
  1. Body Weight
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  2. Body Weights and Measures
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  3. Body Weights and Measures
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: LHCGR
Diseases sorted by gene-association score: precocious puberty, male* (1679), leydig cell hypoplasia with pseudohermaphroditism* (1550), leydig cell hypoplasia* (429), testotoxicosis* (428), leydig cell hypoplasia/agenesis* (100), precocious puberty (63), infertility (28), leydig cell tumor (28), pseudohermaphroditism (26), amenorrhea (24), familial male-limited precocious puberty (19), hypogonadism (13), penis agenesis (13), lactocele (11), adenoma (9), mccune-albright syndrome, somatic, mosaic (8), testicular germ cell cancer (7), sex differentiation disease (7), ovarian hyperstimulation syndrome (7), estrogen excess (6), hypospadias (3), reproductive system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1.63 RPKM in Esophagus - Muscularis
Total median expression: 6.54 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -24.2070-0.346 Picture PostScript Text
3' UTR -213.96923-0.232 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000276 - 7TM_GPCR_Rhodpsn
IPR017452 - GPCR_Rhodpsn_supfam
IPR002131 - Gphrmn_rcpt
IPR000372 - LRR-contain_N
IPR002273 - LSH_rcpt

Pfam Domains:
PF00001 - 7 transmembrane receptor (rhodopsin family)
PF13306 - Leucine rich repeats (6 copies)

SCOP Domains:
52047 - RNI-like
52058 - L domain-like
52075 - Outer arm dynein light chain 1
81321 - Family A G protein-coupled receptor-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1LUT
- Model

1XUL
- Model


ModBase Predicted Comparative 3D Structure on P22888
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
Gene SorterGene Sorter Gene Sorter  
 RGDEnsemblFlyBase  
 Protein SequenceProtein SequenceProtein Sequence  
 AlignmentAlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004871 signal transducer activity
GO:0004930 G-protein coupled receptor activity
GO:0004963 follicle-stimulating hormone receptor activity
GO:0004964 luteinizing hormone receptor activity
GO:0008528 G-protein coupled peptide receptor activity
GO:0016500 protein-hormone receptor activity
GO:0035472 choriogonadotropin hormone receptor activity
GO:0038106 choriogonadotropin hormone binding

Biological Process:
GO:0001545 primary ovarian follicle growth
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
GO:0007189 adenylate cyclase-activating G-protein coupled receptor signaling pathway
GO:0007190 activation of adenylate cyclase activity
GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway
GO:0008584 male gonad development
GO:0009755 hormone-mediated signaling pathway
GO:0030539 male genitalia development
GO:0032962 positive regulation of inositol trisphosphate biosynthetic process
GO:0042699 follicle-stimulating hormone signaling pathway
GO:0042700 luteinizing hormone signaling pathway
GO:0045670 regulation of osteoclast differentiation
GO:0045762 positive regulation of adenylate cyclase activity
GO:0050890 cognition
GO:0071371 cellular response to gonadotropin stimulus
GO:0071373 cellular response to luteinizing hormone stimulus

Cellular Component:
GO:0005768 endosome
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  LP896193 - Sequence 1057 from Patent EP3253886.
AK123498 - Homo sapiens cDNA FLJ41504 fis, clone BRTHA2008527, moderately similar to LUTROPIN-CHORIOGONADOTROPIC HORMONE RECEPTOR PRECURSOR.
M73746 - Homo sapiens lutropin/choriogonadotropin receptor (LHCGR) mRNA, complete cds.
E05678 - cDNA encoding human LH-hCG(luteinizing hormone-human choriogonadotropic hormone)receptor.
M63108 - Human luteinizing hormone-choriogonadrotropin receptor mRNA, complete cds.
JD553685 - Sequence 534709 from Patent EP1572962.
JD345170 - Sequence 326194 from Patent EP1572962.
JD084769 - Sequence 65793 from Patent EP1572962.
JD411136 - Sequence 392160 from Patent EP1572962.
BC157028 - Synthetic construct Homo sapiens clone IMAGE:100063266, MGC:190727 luteinizing hormone/choriogonadotropin receptor (LHCGR) mRNA, encodes complete protein.
S57793 - Homo sapiens luteinizing hormone receptor mRNA, complete cds.
BC156303 - Synthetic construct Homo sapiens clone IMAGE:100061765, MGC:190094 luteinizing hormone/choriogonadotropin receptor (LHCGR) mRNA, encodes complete protein.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04020 - Calcium signaling pathway
hsa04080 - Neuroactive ligand-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein P22888 (Reactome details) participates in the following event(s):

R-HSA-391377 Luteinizing hormone receptor can bind LH
R-HSA-744886 The Ligand:GPCR:Gs complex dissociates
R-HSA-744887 Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs
R-HSA-379044 Liganded Gs-activating GPCR acts as a GEF for Gs
R-HSA-375281 Hormone ligand-binding receptors
R-HSA-418555 G alpha (s) signalling events
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-388396 GPCR downstream signalling
R-HSA-500792 GPCR ligand binding
R-HSA-372790 Signaling by GPCR
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: LCGR, LGR2, LHRHR, LSHR_HUMAN, NM_000233, NP_000224, P22888, Q14751, Q15996, Q9UEW9
UCSC ID: uc002rwu.4
RefSeq Accession: NM_000233
Protein: P22888 (aka LSHR_HUMAN)
CCDS: CCDS1842.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000233.3
exon count: 11CDS single in 3' UTR: no RNA size: 3093
ORF size: 2100CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4400.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.