GH1

growth hormone 1, the group of Growth hormone family

Basic information

Region (hg38): 17:63917200-63918839

Links

ENSG00000259384 ∙ NCBI:2688 ∙ OMIM:139250 ∙ HGNC:4261 ∙ Uniprot:P01241 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the GH1 gene.

• not provided (4 variants)
• Autosomal dominant isolated somatotropin deficiency (4 variants)
• Idiopathic growth hormone deficiency (1 variants)
• Short stature due to growth hormone qualitative anomaly;Isolated growth hormone deficiency type IB;Ateleiotic dwarfism;Autosomal dominant isolated somatotropin deficiency (1 variants)
• Ateleiotic dwarfism (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.

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			5	16		21
missense	1	4	48	6		59
nonsense	1					1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)	4		1			5
splice region	1		1			2
non coding			6	16	5	27
Total	6	4	61	38	5

Highest pathogenic variant AF is 0.00000657

Variants in GH1

This is a list of pathogenic ClinVar variants found in the GH1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-63917314-AGCCACAGCT-A		Autosomal dominant isolated somatotropin deficiency	Uncertain significance (Jul 22, 2024)
17-63917324-G-A		GH1-related disorder	Likely benign (Jul 01, 2019)
17-63917337-C-T		Autosomal dominant isolated somatotropin deficiency	Pathogenic (Oct 24, 2023)
17-63917338-G-A			Uncertain significance (Nov 09, 2023)
17-63917348-G-C		not specified	Uncertain significance (Dec 21, 2023)
17-63917366-G-C		Decreased response to growth hormone stimulation test • not specified	Conflicting classifications of pathogenicity (Apr 18, 2024)
17-63917375-C-T		Ateleiotic dwarfism	Uncertain significance (Dec 24, 2019)
17-63917400-A-G		Decreased response to growth hormone stimulation test	Uncertain significance (Jan 12, 2018)
17-63917402-C-T		Decreased response to growth hormone stimulation test	Uncertain significance (Jan 12, 2018)
17-63917404-C-T		Decreased response to growth hormone stimulation test	Uncertain significance (Jan 13, 2018)
17-63917416-G-A		Inborn genetic diseases	Uncertain significance (May 21, 2023)
17-63917417-T-C		Decreased response to growth hormone stimulation test	Conflicting classifications of pathogenicity (Mar 27, 2023)
17-63917428-C-G		Decreased response to growth hormone stimulation test	Uncertain significance (Dec 27, 2022)
17-63917432-G-A		Inborn genetic diseases	Likely benign (Jan 17, 2024)
17-63917434-G-C		not specified	Uncertain significance (Jul 08, 2024)
17-63917446-C-G			Uncertain significance (Feb 20, 2023)
17-63917447-G-A		GH1-related disorder • Inborn genetic diseases	Likely benign (Dec 18, 2023)
17-63917453-G-C			Uncertain significance (Sep 18, 2023)
17-63917461-T-A		Ateleiotic dwarfism	Uncertain significance (Oct 15, 2023)
17-63917470-A-G		not specified	Uncertain significance (Jul 09, 2024)
17-63917485-G-A		Decreased response to growth hormone stimulation test	Uncertain significance (Jul 18, 2022)
17-63917489-G-A			Likely benign (Nov 30, 2023)
17-63917490-C-A			Uncertain significance (Sep 14, 2022)
17-63917493-C-T		Decreased response to growth hormone stimulation test	Uncertain significance (Jan 13, 2018)
17-63917495-A-G		Decreased response to growth hormone stimulation test	Conflicting classifications of pathogenicity (Jul 18, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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