GH1
growth hormone 1, the group of Growth hormone family
Basic information
Region (hg38): 17:63917200-63918839
Links
Phenotypes
GenCC
Source:
- short stature due to growth hormone qualitative anomaly (Supportive), mode of inheritance: AR
- isolated growth hormone deficiency type IA (Supportive), mode of inheritance: AR
- isolated growth hormone deficiency type IB (Supportive), mode of inheritance: AR
- isolated growth hormone deficiency type II (Supportive), mode of inheritance: AD
- isolated growth hormone deficiency type II (Strong), mode of inheritance: AD
- isolated growth hormone deficiency type IA (Strong), mode of inheritance: AR
- isolated growth hormone deficiency type IA (Definitive), mode of inheritance: AR
- isolated growth hormone deficiency type II (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Isolated growth hormone deficiency, type IA; Isolated growth hormone deficiency, type 1B; Isolated growth hormone deficiency, type II; Kowarski syndrome | AD/AR | Endocrine | Some individuals respond well to exogenous GH treatment, and benefits may be increased with early diagnosis and treatment | Endocrine | 7714096; 8530604; 9076339; 9024229; 9024235; 8552145; 9276733; 9435425; 10678654; 11443201; 12915652; 12655557; 15713716; 16060904; 15671105; 17785701; 18554279; 17925337; 20852587 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (89 variants)
- Decreased_response_to_growth_hormone_stimulation_test (39 variants)
- Inborn_genetic_diseases (28 variants)
- Autosomal_dominant_isolated_somatotropin_deficiency (26 variants)
- not_specified (25 variants)
- Ateleiotic_dwarfism (17 variants)
- Isolated_growth_hormone_deficiency_type_IB (10 variants)
- GH1-related_disorder (10 variants)
- Short_stature_due_to_growth_hormone_qualitative_anomaly (9 variants)
- Idiopathic_growth_hormone_deficiency (2 variants)
- Isolated_congenital_growth_hormone_deficiency (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GH1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000515.5. 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 | 28 | 34 | ||||
| missense | 66 | 86 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 7 | |||||
| Total | 14 | 7 | 74 | 36 | 0 |
Highest pathogenic variant AF is 0.00000342023
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GH1 | protein_coding | protein_coding | ENST00000323322 | 5 | 1620 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0301 | 0.929 | 125735 | 1 | 10 | 125746 | 0.0000437 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.939 | 148 | 119 | 1.24 | 0.00000775 | 1411 |
| Missense in Polyphen | 32 | 33.366 | 0.95905 | 465 | ||
| Synonymous | -2.80 | 81 | 54.7 | 1.48 | 0.00000386 | 429 |
| Loss of Function | 1.76 | 4 | 10.0 | 0.399 | 5.40e-7 | 107 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000905 | 0.0000904 |
| Ashkenazi Jewish | 0.000198 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.0000264 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000131 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.;
- Disease
- DISEASE: Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400]: An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone. {ECO:0000269|PubMed:8364549}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]: An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:12655557}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Kowarski syndrome (KWKS) [MIM:262650]: A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy. {ECO:0000269|PubMed:17519310, ECO:0000269|PubMed:8552145, ECO:0000269|PubMed:9276733}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100]: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:11502836, ECO:0000269|PubMed:9152628}. 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;Adipogenesis;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;Prolactin receptor signaling;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Growth hormone signaling;Immune System;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;growth hormone signaling pathway;GPCR signaling-G alpha i
(Consensus)
Recessive Scores
- pRec
- 0.251
Intolerance Scores
- loftool
- 0.0442
- rvis_EVS
- 0.31
- rvis_percentile_EVS
- 72.6
Haploinsufficiency Scores
- pHI
- 0.106
- hipred
- N
- hipred_score
- 0.240
- ghis
- 0.435
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.958
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gh
- Phenotype
- endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism 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); hematopoietic system 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); reproductive system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- gh1
- Affected structure
- fat cell
- Phenotype tag
- abnormal
- Phenotype quality
- hypertrophic
Gene ontology
- Biological process
- positive regulation of receptor internalization;regulation of signaling receptor activity;positive regulation of activation of Janus kinase activity;positive regulation of glucose transmembrane transport;positive regulation of phosphatidylinositol 3-kinase signaling;response to nutrient levels;response to estradiol;positive regulation of multicellular organism growth;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of MAP kinase activity;positive regulation of insulin-like growth factor receptor signaling pathway;positive regulation of growth;positive regulation of JAK-STAT cascade;animal organ development;positive regulation of peptidyl-tyrosine phosphorylation;growth hormone receptor signaling pathway;JAK-STAT cascade involved in growth hormone signaling pathway;bone maturation
- Cellular component
- extracellular region;extracellular space;endosome lumen;collagen-containing extracellular matrix;growth hormone receptor complex
- Molecular function
- growth hormone receptor binding;prolactin receptor binding;hormone activity;protein binding;growth factor activity;metal ion binding