GHR
growth hormone receptor, the group of Fibronectin type III domain containing
Basic information
Region (hg38): 5:42423439-42721878
Links
Phenotypes
GenCC
Source:
- Laron syndrome (Definitive), mode of inheritance: AR
- Laron syndrome (Supportive), mode of inheritance: AR
- short stature due to partial GHR deficiency (Supportive), mode of inheritance: Unknown
- short stature due to partial GHR deficiency (Strong), mode of inheritance: AD
- Laron syndrome (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Growth hormone insensitivity syndrome (Laron syndrome) | AD/AR | Endocrine | Medical treatment (eg, with recombinant human IGF1) can be beneficial | Endocrine | 5707789; 4470894; 1349669; 8488849; 7565946; 8784089; 9140387; 9024266; 9360502; 9851797; 11297575; 11468686; 12679461; 15001620; 17148568; 18404972; 18073295; 19789204; 20583548; 19812236; 20606392; 20962506; 21325617; 21396571; 21900382; 22117696; 22423513; 22587301; 23006617 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (18 variants)
- Laron-type isolated somatotropin defect (10 variants)
- Growth hormone insensitivity syndrome (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GHR gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 116 | 124 | ||||
| missense | 128 | 145 | ||||
| nonsense | 11 | |||||
| start loss | 1 | |||||
| frameshift | 9 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 7 | |||||
| splice region | 1 | 2 | 3 | 12 | 18 | |
| non coding | 37 | 42 | 36 | 117 | ||
| Total | 21 | 9 | 173 | 164 | 48 |
Highest pathogenic variant AF is 0.0000658
Variants in GHR
This is a list of pathogenic ClinVar variants found in the GHR region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-42423791-A-G | Laron-type isolated somatotropin defect | Uncertain significance (Jan 13, 2018) | ||
| 5-42423803-A-G | Laron-type isolated somatotropin defect | Benign (Jun 11, 2020) | ||
| 5-42423817-C-A | Laron-type isolated somatotropin defect | Likely benign (Jan 12, 2018) | ||
| 5-42423849-C-T | Laron-type isolated somatotropin defect | Uncertain significance (Jan 13, 2018) | ||
| 5-42423878-G-T | Laron-type isolated somatotropin defect | Uncertain significance (Jan 13, 2018) | ||
| 5-42423891-C-T | Laron-type isolated somatotropin defect | Uncertain significance (Jan 12, 2018) | ||
| 5-42423893-C-T | Laron-type isolated somatotropin defect | Uncertain significance (Jan 13, 2018) | ||
| 5-42423928-G-C | Laron-type isolated somatotropin defect | Benign (Jan 12, 2018) | ||
| 5-42424171-A-AGTGT | Benign (Jun 19, 2021) | |||
| 5-42424171-A-AGTGTGT | Benign (Jun 19, 2021) | |||
| 5-42424598-G-A | Short stature due to partial GHR deficiency | Uncertain significance (Dec 04, 2019) | ||
| 5-42424601-A-T | GHR-related disorder | Benign (Oct 31, 2019) | ||
| 5-42565741-C-T | Benign (Nov 12, 2018) | |||
| 5-42565863-G-C | not specified | Uncertain significance (Jun 11, 2024) | ||
| 5-42565865-T-C | Laron-type isolated somatotropin defect | Uncertain significance (Jan 13, 2018) | ||
| 5-42565869-A-G | Laron-type isolated somatotropin defect | Uncertain significance (Jan 13, 2018) | ||
| 5-42565875-A-G | Pathogenic (Mar 09, 2023) | |||
| 5-42565883-C-T | Likely benign (Aug 20, 2022) | |||
| 5-42565885-G-A | Pathogenic (Feb 14, 2023) | |||
| 5-42565886-G-C | Laron-type isolated somatotropin defect | Uncertain significance (Mar 30, 2009) | ||
| 5-42565892-G-T | Likely benign (Aug 16, 2023) | |||
| 5-42565895-G-A | Likely benign (Jan 08, 2024) | |||
| 5-42565899-A-G | Uncertain significance (Nov 15, 2022) | |||
| 5-42565907-A-C | Likely benign (Dec 01, 2023) | |||
| 5-42565908-C-T | Likely benign (Aug 07, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GHR | protein_coding | protein_coding | ENST00000230882 | 9 | 298101 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0000844 | 0.999 | 125708 | 0 | 40 | 125748 | 0.000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.361 | 346 | 328 | 1.06 | 0.0000158 | 4222 |
| Missense in Polyphen | 137 | 142.31 | 0.96269 | 1889 | ||
| Synonymous | -0.305 | 125 | 121 | 1.04 | 0.00000618 | 1199 |
| Loss of Function | 2.97 | 12 | 29.4 | 0.408 | 0.00000145 | 360 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000395 | 0.000395 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000248 | 0.000246 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity). {ECO:0000250}.; FUNCTION: Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.;
- Disease
- DISEASE: Laron syndrome (LARS) [MIM:262500]: A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone. {ECO:0000269|PubMed:10870033, ECO:0000269|PubMed:14678285, ECO:0000269|PubMed:2779634, ECO:0000269|PubMed:8137822, ECO:0000269|PubMed:8450064, ECO:0000269|PubMed:8504296, ECO:0000269|PubMed:9024232, ECO:0000269|PubMed:9661642, ECO:0000269|PubMed:9851797}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Growth hormone insensitivity, partial (GHIP) [MIM:604271]: A disease characterized by partial resistance to growth hormone resulting in short stature. Short stature is defined by a standing height more than 2 standard deviations below the mean (or below the 2.5 percentile) for sex and chronological age, compared with a well-nourished, healthy, genetically relevant population. {ECO:0000269|PubMed:7565946}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;JAK-STAT;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Endochondral Ossification;mtor signaling pathway;trefoil factors initiate mucosal healing;regulation of eif-4e and p70s6 kinase;Growth hormone receptor signaling;akt signaling pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Growth hormone signaling;Immune System;growth hormone signaling pathway;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;Notch-mediated HES/HEY network
(Consensus)
Recessive Scores
- pRec
- 0.528
Intolerance Scores
- loftool
- 0.210
- rvis_EVS
- 0.76
- rvis_percentile_EVS
- 86.8
Haploinsufficiency Scores
- pHI
- 0.382
- hipred
- Y
- hipred_score
- 0.553
- ghis
- 0.418
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.579
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Ghr
- Phenotype
- embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Gene ontology
- Biological process
- activation of MAPK activity;endocytosis;JAK-STAT cascade;cytokine-mediated signaling pathway;taurine metabolic process;cellular response to hormone stimulus;regulation of multicellular organism growth;positive regulation of multicellular organism growth;hormone metabolic process;positive regulation of tyrosine phosphorylation of STAT protein;activation of Janus kinase activity;positive regulation of JAK-STAT cascade;insulin-like growth factor receptor signaling pathway;positive regulation of peptidyl-tyrosine phosphorylation;growth hormone receptor signaling pathway;JAK-STAT cascade involved in growth hormone signaling pathway
- Cellular component
- extracellular region;extracellular space;cytosol;plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell surface;integral component of membrane;cytoplasmic ribonucleoprotein granule;receptor complex;growth hormone receptor complex
- Molecular function
- cytokine receptor activity;growth hormone receptor activity;protein binding;peptide hormone binding;growth factor binding;protein kinase binding;cytokine binding;identical protein binding;protein homodimerization activity;proline-rich region binding