GAS1
protein-codinggrowth arrest specific 1
Gene summary
Growth arrest-specific 1 plays a role in growth suppression. GAS1 blocks entry to S phase and prevents cycling of normal and transformed cells. Gas1 is a putative tumor suppressor gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0016296
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0016296
Submitter: ClinGen
GAS1 was first reported in relation to autosomal dominant holoprosencephaly in 2010 (Ribero et al., PMID: 20583117). GAS1 has been associated with the phenotypic spectrum of holoprosencephaly in the literature and has therefore been curated for this disease relationship. 10 missense variants have been reported in 10 probands in 2 publications (PMIDs: 20583117, 21842183), of which one is included in this curation. The mechanism of pathogenicity appears to be loss o function. GAS1 and SHH have been reported to physically interact with variants in GAS1 suggesting a decrease in SHH downstream signaling cascades (PMID: 17525797). This gene-disease association is also supported by aminal models (PMIDs: 17525797, 17504940). GAS1 -/- mice were observed to recapitulate some phenotypic features of microform holoprosencephaly, midfacial hypoplasia, and cleft palate, in addition to additional craniofacial malformations. Interestingly, Gas1−/−; Shh−/− mice were not found at birth, suggesting embryonic lethality, while Gas1+/−; Shh+/− mice were phenotypically normal. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Brain Malformations GCEP on the meeting date 01/10/2023 (SOP Version 9).
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Endocrine; Neurologic
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
Comments: Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GAS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002048.3. 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 | 5 | 29 | 1 | 35 | ||
| missense | 82 | 3 | 1 | 86 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 88 | 32 | 2 | 122 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002039.2 | 1 | MANE Select | |
| Ensembl | ENSP00000298743.7 | 1 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hedgehog signaling pathway - Homo sapiens (human)
- HH-Ncore
- Hedgehog Signaling Pathway
- Signal Transduction
- Ligand-receptor interactions
Biological Process
- cell cycle arrest
- regulation of smoothened signaling pathway
- negative regulation of protein processing
- cellular response to vascular endothelial growth factor stimulus
- regulation of apoptotic process
Molecular Function
- protein binding
Cellular Component
- plasma membrane
- integral component of membrane
- anchored component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000298743
- Coding exons
- 1
- Length
- 2826
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.747 | 110 | 134 | 0.819 | 0.00000633 | 2126 |
| Missense (PolyPhen) | 28 | 48.425 | 0.57821 | 690 | ||
| Synonymous | -3.42 | 95 | 61.1 | 1.56 | 0.00000309 | 758 |
| Loss of Function | 2.20 | 0 | 5.65 | 0.00 | 2.45e-7 | 84 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specific growth arrest protein involved in growth suppression. Blocks entry to S phase. Prevents cycling of normal and transformed cells. {ECO:0000269|PubMed:8127893}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |