GAS6
protein-codinggrowth arrest specific 6, the group of Gla domain containing
Gene summary
This gene encodes a gamma-carboxyglutamic acid (Gla)-containing protein thought to be involved in the stimulation of cell proliferation. This gene is frequently overexpressed in many cancers and has been implicated as an adverse prognostic marker. Elevated protein levels are additionally associated with a variety of disease states, including venous thromboembolic disease, systemic lupus erythematosus, chronic renal failure, and preeclampsia. [provided by RefSeq, Aug 2014]
- AXLLG
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GAS6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000820.4. 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 | 3 | 2 | 3 | 8 | ||
| missense | 112 | 10 | 5 | 127 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 119 | 12 | 8 | 139 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000811.1 | 15 | MANE Select | |
| Ensembl | ENSP00000331831.6 | 15 | MANE Select | |
| Ensembl | ENSP00000551779.1 | 16 | Standard | |
| Ensembl | ENSP00000551780.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gas6 | Danio rerio | Structure: dorsal longitudinal anastomotic vessel Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Warfarin Pathway, Pharmacodynamics
- Ebola Virus Pathway on Host
- Ebola Virus Pathway on Host
- Post-translational protein phosphorylation
- Post-translational protein modification
Biological Process
- neuron migration
- positive regulation of protein phosphorylation
- positive regulation of cytokine-mediated signaling pathway
- platelet degranulation
- positive regulation of glomerular filtration
Molecular Function
- phosphatidylserine binding
- signaling receptor binding
- voltage-gated calcium channel activity
- calcium ion binding
- protein binding
Cellular Component
- extracellular region
- extracellular space
- cytoplasm
- endoplasmic reticulum lumen
- Golgi lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000327773
- Coding exons
- 15
- Length
- 43525
- Individuals with no LoFs
- 125676
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125696
- p
- 0.0000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.19 | 344 | 412 | 0.835 | 0.0000275 | 4366 |
| Missense (PolyPhen) | 149 | 197.43 | 0.75472 | 2095 | ||
| Synonymous | -0.103 | 193 | 191 | 1.01 | 0.0000151 | 1357 |
| Loss of Function | 3.80 | 9 | 32.3 | 0.278 | 0.00000163 | 369 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00012 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. {ECO:0000269|PubMed:12364394, ECO:0000269|PubMed:18840707}.;
Recessive Scores
- pRec
- 0.266
Intolerance Scores
- LoFtool
- 0.327
- RVIS EVS
- -0.44
- RVIS percentile EVS
- 24.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.736
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |