GHSR

growth hormone secretagogue receptor, the group of Peptide receptors

Basic information

Region (hg38): 3:172443291-172448456

Links

ENSG00000121853 ∙ NCBI:2693 ∙ OMIM:601898 ∙ HGNC:4267 ∙ Uniprot:Q92847 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short stature due to GHSR deficiency (Moderate), mode of inheritance: Semidominant
• short stature due to GHSR deficiency (Supportive), mode of inheritance: AD
• short stature due to GHSR deficiency (Limited), mode of inheritance: AR
• short stature due to GHSR deficiency (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short stature	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	16511605; 19789204; 21646290

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GHSR gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GHSR 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			3	35	8	46
missense			89	3	1	93
nonsense			4			4
start loss						0
frameshift			8			8
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			27	11	13	51
Total	0	0	131	49	22

Variants in GHSR

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

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

Position	Type	Phenotype	Significance	ClinVar
3-172443304-C-T		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172443329-C-T		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172443346-G-C		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172443356-C-T		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 12, 2018)
3-172443386-C-T		Short stature due to growth hormone secretagogue receptor deficiency	Likely benign (Jan 13, 2018)
3-172443425-T-C		Short stature due to growth hormone secretagogue receptor deficiency	Benign (Jan 13, 2018)
3-172443433-T-C		Short stature due to growth hormone secretagogue receptor deficiency	Likely benign (Jan 13, 2018)
3-172443449-A-T		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172443481-TTATC-T		Short stature due to partial GHR deficiency	Likely benign (Jun 14, 2016)
3-172443553-G-A		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172443607-G-A		Short stature due to partial GHR deficiency	Uncertain significance (Jun 14, 2016)
3-172443629-G-C		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 12, 2018)
3-172443655-G-T		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172443716-T-C		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Mar 16, 2018)
3-172443816-C-A		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 12, 2018)
3-172443853-A-C		Short stature due to growth hormone secretagogue receptor deficiency	Benign (Jan 13, 2018)
3-172443893-A-G		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172444000-G-A		Short stature due to growth hormone secretagogue receptor deficiency	Likely benign (Jan 12, 2018)
3-172444003-C-T		Short stature due to growth hormone secretagogue receptor deficiency	Likely benign (Jan 12, 2018)
3-172444052-C-A		Short stature due to growth hormone secretagogue receptor deficiency	Benign (Jan 13, 2018)
3-172444088-T-C		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172444115-A-T		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172444137-C-G		Short stature due to growth hormone secretagogue receptor deficiency	Benign (Jan 12, 2018)
3-172444211-T-G		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)
3-172444319-A-T		Short stature due to growth hormone secretagogue receptor deficiency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GHSR	protein_coding	protein_coding	ENST00000241256	2	3324

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00658	0.921	125721	0	26	125747	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.190	212	220	0.964	0.0000128	2364
Missense in Polyphen		63	74.868	0.84148		816
Synonymous	-1.26	116	99.9	1.16	0.00000628	783
Loss of Function	1.55	5	10.4	0.481	5.36e-7	102

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000204	0.000204
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.00	0.00
South Asian	0.0000981	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for ghrelin, coupled to G-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-peptide, low molecular weight secretagogues (e.g. L-692,429, MK-0677, adenosine). {ECO:0000269|PubMed:10604470, ECO:0000269|PubMed:11322507}.
• Pathway: cAMP signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Peptide GPCRs;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;Ghrelin;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.224

Intolerance Scores

• loftool: 0.429
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.92

Haploinsufficiency Scores

• pHI: 0.589
• hipred: Y
• hipred_score: 0.651
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.276

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ghsr
• Phenotype: digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;spermatogenesis;learning or memory;actin polymerization or depolymerization;adult feeding behavior;response to hormone;hormone-mediated signaling pathway;negative regulation of norepinephrine secretion;growth hormone secretion;response to food;negative regulation of appetite;positive regulation of appetite;response to follicle-stimulating hormone;response to estradiol;negative regulation of interleukin-1 beta production;cellular response to insulin stimulus;ghrelin secretion;positive regulation of multicellular organism growth;negative regulation of tumor necrosis factor biosynthetic process;regulation of hindgut contraction;positive regulation of insulin-like growth factor receptor signaling pathway;negative regulation of interleukin-6 biosynthetic process;positive regulation of fatty acid metabolic process;negative regulation of insulin secretion;decidualization;negative regulation of inflammatory response;regulation of synapse assembly;regulation of transmission of nerve impulse;regulation of growth hormone secretion;response to growth hormone;cellular response to lipopolysaccharide;response to dexamethasone;negative regulation of locomotion involved in locomotory behavior;cellular response to thyroid hormone stimulus;regulation of neurotransmitter receptor localization to postsynaptic specialization membrane;postsynaptic modulation of chemical synaptic transmission;regulation of postsynapse organization;positive regulation of small intestinal transit;positive regulation of sprouting angiogenesis;positive regulation of eating behavior;response to monosodium glutamate;positive regulation of small intestine smooth muscle contraction;negative regulation of tumor necrosis factor secretion;regulation of gastric motility;positive regulation of vascular endothelial cell proliferation;cellular response to insulin-like growth factor stimulus;negative regulation of macrophage apoptotic process
• Cellular component: plasma membrane;cell surface;neuron projection;membrane raft;Schaffer collateral - CA1 synapse;postsynapse;glutamatergic synapse;integral component of synaptic membrane
• Molecular function: growth hormone secretagogue receptor activity;G protein-coupled receptor activity;growth hormone-releasing hormone receptor activity;peptide hormone binding