GHSR
protein-codinggrowth hormone secretagogue receptor, the group of Peptide receptors
Gene summary
This gene encodes a member of the G-protein coupled receptor family. The encoded protein may play a role in energy homeostasis and regulation of body weight. Two identified transcript variants are expressed in several tissues and are evolutionary conserved in fish and swine. One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the Ghrelin ligand and defines a neuroendocrine pathway for growth hormone release. The second transcript (1b) retains the intron and does not function as a receptor for Ghrelin; however, it may function to attenuate activity of isoform 1a. Mutations in this gene are associated with autosomal idiopathic short stature.[provided by RefSeq, Apr 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014403
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0014403
Submitter: Orphanet
Inheritance Pattern: SD
Disease ID:MONDO:0014403
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0014403
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014403
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014403
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GHSR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198407.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 56 | 3 | 61 | ||
| missense | 3 | 150 | 9 | 162 | ||
| nonsense | 1 | 5 | 6 | |||
| start loss | 0 | |||||
| frameshift | 11 | 11 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 1 | 3 | 170 | 65 | 3 | 242 |
Highest pathogenic variant AF is 0.00003346015
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_940799.1 | 2 | MANE Select | |
| Ensembl | ENSP00000241256.2 | 2 | MANE Select | |
| RefSeq | NP_004113.1 | 1 | Standard | |
| Ensembl | ENSP00000395344.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- cAMP signaling pathway - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Peptide GPCRs
- GPCRs, Class A Rhodopsin-like
- Signaling by GPCR
Biological Process
- G protein-coupled receptor signaling pathway
- spermatogenesis
- learning or memory
- actin polymerization or depolymerization
- adult feeding behavior
Molecular Function
- growth hormone secretagogue receptor activity
- G protein-coupled receptor activity
- growth hormone-releasing hormone receptor activity
- peptide hormone binding
Cellular Component
- plasma membrane
- cell surface
- neuron projection
- membrane raft
- Schaffer collateral - CA1 synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000241256
- Coding exons
- 2
- Length
- 3324
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125747
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.190 | 212 | 220 | 0.964 | 0.0000128 | 2364 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.224
Intolerance Scores
- LoFtool
- 0.429
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 46.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.276
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |