GHR

growth hormone receptor, the group of Fibronectin type III domain containing

Basic information

Region (hg38): 5:42423438-42721878

Links

ENSG00000112964 ∙ NCBI:2690 ∙ OMIM:600946 ∙ HGNC:4263 ∙ Uniprot:P10912 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the GHR gene.

• not provided (232 variants)
• Laron-type isolated somatotropin defect (116 variants)
• not specified (20 variants)
• Inborn genetic diseases (14 variants)
• Short stature due to partial GHR deficiency (11 variants)
• See cases (3 variants)
• GHR-related condition (3 variants)
• Growth hormone insensitivity syndrome (2 variants)
• 7 conditions (1 variants)
• Short stature due to partial GHR deficiency;Laron-type isolated somatotropin defect;Hypercholesterolemia, familial, 1 (1 variants)
• Short stature due to partial GHR deficiency;Laron-type isolated somatotropin defect;Short stature due to growth hormone secretagogue receptor deficiency;Hypercholesterolemia, familial, 1 (1 variants)
• Hypercholesterolemia, familial, 1 (1 variants)
• Laron-type isolated somatotropin defect;Short stature due to partial GHR deficiency (1 variants)
• Short stature due to partial GHR deficiency;Laron-type isolated somatotropin defect (1 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	1		3	47	4	55
missense	1	3	108	4	6	122
nonsense	6	1				7
start loss	1					1
frameshift	4	3	2			9
inframe indel						0
splice donor/acceptor (+/-2bp)	5		1			6
splice region	1	2	3	6		12
non coding	1	1	36	20	34	92
Total	19	8	150	71	44

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			Uncertain significance (Nov 09, 2019)
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: gnomAD

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: dbNSFP

• 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