LHCGR
luteinizing hormone/choriogonadotropin receptor, the group of Glycoprotein hormone receptors
Basic information
Region (hg38): 2:48686774-48755730
Previous symbols: [ "HHG" ]
Links
Phenotypes
GenCC
Source:
- familial male-limited precocious puberty (Supportive), mode of inheritance: AD
- Leydig cell hypoplasia, type 1 (Strong), mode of inheritance: AR
- familial male-limited precocious puberty (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Leydig cell hypoplasia type I; Leydig cell hypoplasia type II; Luteinizing hormone resistance, female; Precocious puberty, male | AR | Endocrine; Genitourinary; Oncologic | In mild forms of LCH, the disorder may not be clinically recognized early, and exogenous testosterone can result in normal virilization; In Precocious puberty, male, medical therapy (eg, with combined spironolactone and testolactone) has been reported as beneficial; Surveillance for related neoplasms (eg, testicular neoplasms) may allow prompt diagnosis and treatment | Endocrine; Genitourinary; Oncologic | 184390; 6792847; 3557461; 3812586; 2492636; 7692306; 7719343; 7581384; 8559204; 8923827; 9703386; 9817592; 10580072; 10714363; 10704433; 11391350; 11857565; 19129711; 21060208; 21683950; 21720050; 22369774; 22931948 |
| Both germline and somatic variants have been described |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (118 variants)
- Leydig_cell_agenesis (66 variants)
- Inborn_genetic_diseases (59 variants)
- Gonadotropin-independent_familial_sexual_precocity (53 variants)
- Hypergonadotropic_hypogonadism (15 variants)
- LHCGR-related_disorder (14 variants)
- not_specified (10 variants)
- Luteinizing_hormone_resistance,_female (4 variants)
- Leydig_cell_hypoplasia,_type_II (3 variants)
- Disorder_of_sexual_differentiation (2 variants)
- See_cases (2 variants)
- Precocious_puberty_in_males (2 variants)
- Pseudohermaphroditism (1 variants)
- 46,XY_disorder_of_sex_development (1 variants)
- Leydig_cell_adenoma,_somatic,_with_male-limited_precocious_puberty (1 variants)
- Leydig_hypoplasia,_type_I (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LHCGR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000233.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 22 | 29 | ||||
| missense | 22 | 10 | 95 | 15 | 142 | |
| nonsense | 10 | |||||
| start loss | 0 | |||||
| frameshift | 5 | |||||
| splice donor/acceptor (+/-2bp) | 7 | |||||
| Total | 32 | 22 | 99 | 37 | 3 |
Highest pathogenic variant AF is 0.0000932133
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LHCGR | protein_coding | protein_coding | ENST00000294954 | 11 | 123453 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 5.30e-8 | 0.962 | 125691 | 0 | 57 | 125748 | 0.000227 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.163 | 350 | 359 | 0.976 | 0.0000182 | 4543 |
| Missense in Polyphen | 110 | 120.06 | 0.91621 | 1604 | ||
| Synonymous | -0.0419 | 141 | 140 | 1.00 | 0.00000726 | 1398 |
| Loss of Function | 2.02 | 16 | 27.4 | 0.584 | 0.00000142 | 353 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000358 | 0.000358 |
| Ashkenazi Jewish | 0.000397 | 0.000397 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000291 | 0.000290 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.000490 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Receptor for lutropin-choriogonadotropic hormone (PubMed:11847099). The activity of this receptor is mediated by G proteins which activate adenylate cyclase (PubMed:11847099). {ECO:0000269|PubMed:11847099}.;
- Disease
- DISEASE: Familial male precocious puberty (FMPP) [MIM:176410]: In FMPP the receptor is constitutively activated. {ECO:0000269|PubMed:11134146, ECO:0000269|PubMed:11391350, ECO:0000269|PubMed:7629248, ECO:0000269|PubMed:7692306, ECO:0000269|PubMed:7714085, ECO:0000269|PubMed:7757065, ECO:0000269|PubMed:8281137, ECO:0000269|PubMed:8829636, ECO:0000269|PubMed:8929952, ECO:0000269|PubMed:9467560, ECO:0000269|PubMed:9661624}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Luteinizing hormone resistance (LHR) [MIM:238320]: 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. {ECO:0000269|PubMed:12050206, ECO:0000269|PubMed:15372531, ECO:0000269|PubMed:15472221, ECO:0000269|PubMed:19551906, ECO:0000269|PubMed:7719343, ECO:0000269|PubMed:8559204, ECO:0000269|PubMed:9215288, ECO:0000269|PubMed:9514160, ECO:0000269|PubMed:9626144, ECO:0000269|PubMed:9626653}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Calcium signaling pathway - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Intracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/Choriogonadotropin;Peptide GPCRs;Ovarian Infertility Genes;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Hormone ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR downstream signalling;Arf6 signaling events
(Consensus)
Recessive Scores
- pRec
- 0.426
Intolerance Scores
- loftool
- 0.283
- rvis_EVS
- 0.36
- rvis_percentile_EVS
- 74.63
Haploinsufficiency Scores
- pHI
- 0.130
- hipred
- N
- hipred_score
- 0.410
- ghis
- 0.441
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.668
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Lhcgr
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; normal phenotype; reproductive system phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- lhcgr
- Affected structure
- postovulatory follicle
- Phenotype tag
- abnormal
- Phenotype quality
- increased amount
Gene ontology
- Biological process
- G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;adenylate cyclase-activating G protein-coupled receptor signaling pathway;activation of adenylate cyclase activity;phospholipase C-activating G protein-coupled receptor signaling pathway;male gonad development;hormone-mediated signaling pathway;ovulation cycle process;male genitalia development;positive regulation of inositol trisphosphate biosynthetic process;luteinizing hormone signaling pathway;positive regulation of adenylate cyclase activity;cognition;cellular response to gonadotropin stimulus;cellular response to luteinizing hormone stimulus
- Cellular component
- endosome;plasma membrane;integral component of plasma membrane
- Molecular function
- luteinizing hormone receptor activity;G protein-coupled peptide receptor activity;choriogonadotropin hormone receptor activity;choriogonadotropin hormone binding