GHRL

ghrelin and obestatin prepropeptide, the group of Neuropeptides

Basic information

Region (hg38): 3:10285665-10292947

Links

ENSG00000157017 ∙ NCBI:51738 ∙ OMIM:605353 ∙ HGNC:18129 ∙ Uniprot:Q9UBU3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• not provided (8 variants)
• Inborn genetic diseases (7 variants)
• Obesity (3 variants)
• Obesity, age at onset of (1 variants)
• Metabolic syndrome, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GHRL 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						0
missense			7	1	1	9
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding					4	4
Total	0	0	9	1	5

Variants in GHRL

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

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

Position	Type	Phenotype	Significance	ClinVar
3-10286566-A-C			Benign (Nov 12, 2018)
3-10286724-A-T		not specified	Uncertain significance (Oct 25, 2022)
3-10286769-T-A		Obesity	Benign (Jun 09, 2021)
3-10286773-C-T		not specified	Uncertain significance (Jan 31, 2022)
3-10286782-GC-G		Obesity	Uncertain significance (Aug 12, 2021)
3-10286799-A-G		not specified	Uncertain significance (Feb 14, 2024)
3-10287098-G-A			Benign (Nov 12, 2018)
3-10287125-T-C			Benign (Nov 12, 2018)
3-10289760-A-C			Uncertain significance (Jul 01, 2022)
3-10289773-G-T		Metabolic syndrome, susceptibility to • Obesity, age at onset of • Obesity	Benign/Likely benign (Apr 19, 2022)
3-10289785-C-A		not specified	Uncertain significance (Dec 26, 2023)
3-10289811-G-A		not specified	Uncertain significance (Aug 17, 2022)
3-10289814-C-T		not specified	Likely benign (Jan 18, 2023)
3-10289820-C-A		not specified	Uncertain significance (Dec 22, 2023)
3-10289835-C-T		Metabolic syndrome, susceptibility to • Obesity	risk factor (Dec 01, 2005)
3-10289914-C-T			Benign (Jun 20, 2021)
3-10290074-T-C		not specified	Uncertain significance (Apr 12, 2023)
3-10290080-C-G		not specified	Uncertain significance (Oct 17, 2023)
3-10290098-A-G		not specified	Uncertain significance (Jun 21, 2023)
3-10292847-C-T		not specified	Uncertain significance (Feb 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GHRL	protein_coding	protein_coding	ENST00000335542	4	7273

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.39e-11	0.00397	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.797	84	65.8	1.28	0.00000362	743
Missense in Polyphen		27	18.339	1.4723		263
Synonymous	0.0896	28	28.6	0.979	0.00000172	233
Loss of Function	-2.19	13	6.82	1.91	3.76e-7	66

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000503	0.000489
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000220	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000979	0.0000967
Middle Eastern	0.000220	0.000217
South Asian	0.000230	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation.
• Pathway: cAMP signaling pathway - Homo sapiens (human);Synthesis, secretion, and deacylation of Ghrelin;Signaling by GPCR;Signal Transduction;Peptide hormone metabolism;Synthesis, secretion, and deacylation of Ghrelin;Metabolism of proteins;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: 0.359

Intolerance Scores

• loftool: 0.973
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.14

Haploinsufficiency Scores

• pHI: 0.0783
• hipred: N
• hipred_score: 0.170

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.753

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ghrl
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; homeostasis/metabolism 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)

Zebrafish Information Network

• Gene name: ghrl
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: activation of MAPK activity;gastric acid secretion;negative regulation of endothelial cell proliferation;glucose metabolic process;G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;actin polymerization or depolymerization;adult feeding behavior;response to hormone;hormone-mediated signaling pathway;regulation of signaling receptor activity;dendrite development;negative regulation of angiogenesis;growth hormone secretion;positive regulation of insulin secretion;regulation of response to food;positive regulation of appetite;negative regulation of interleukin-1 beta production;gastric emptying;positive regulation of insulin secretion involved in cellular response to glucose stimulus;positive regulation of growth rate;negative regulation of locomotion;positive regulation of multicellular organism growth;regulation of cell population proliferation;negative regulation of circadian sleep/wake cycle, REM sleep;negative regulation of tumor necrosis factor biosynthetic process;negative regulation of apoptotic process;cortisol secretion;response to estrogen;negative regulation of interleukin-6 biosynthetic process;positive regulation of circadian sleep/wake cycle, non-REM sleep;negative regulation of insulin secretion;decidualization;negative regulation of inflammatory response;cartilage development;positive regulation of corticotropin secretion;positive regulation of cortisol secretion;response to electrical stimulus;positive regulation of synapse assembly;regulation of transmission of nerve impulse;excitatory postsynaptic potential;positive regulation of growth hormone secretion;positive regulation of growth hormone receptor signaling pathway;positive regulation of protein tyrosine kinase activity;postsynaptic modulation of chemical synaptic transmission;regulation of postsynapse organization;positive regulation of small intestinal transit;positive regulation of cold-induced thermogenesis;positive regulation of bone development;positive regulation of sprouting angiogenesis;positive regulation of eating behavior;positive regulation of adipose tissue development;positive regulation of gastric mucosal blood circulation;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 component: extracellular region;extracellular space;endoplasmic reticulum lumen;axon;secretory granule lumen;Schaffer collateral - CA1 synapse;postsynapse;glutamatergic synapse
• Molecular function: G protein-coupled receptor binding;protein binding;growth hormone-releasing hormone activity;protein tyrosine kinase activator activity;ghrelin receptor binding