AXL
AXL receptor tyrosine kinase, the group of Fibronectin type III domain containing|V-set domain containing|Receptor tyrosine kinases
Basic information
Region (hg38): 19:41219223-41261766
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (145 variants)
- not_specified (85 variants)
- AXL-related_disorder (22 variants)
- Hypogonadotropic_hypogonadism_7_with_or_without_anosmia (2 variants)
- Amenorrhea (2 variants)
- NK-cell_enteropathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the AXL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021913.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 30 | 12 | 45 | |||
| missense | 110 | 16 | 130 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 118 | 46 | 15 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| AXL | protein_coding | protein_coding | ENST00000301178 | 20 | 42564 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0130 | 0.987 | 125712 | 0 | 36 | 125748 | 0.000143 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.44 | 463 | 559 | 0.829 | 0.0000342 | 5743 |
| Missense in Polyphen | 176 | 235.19 | 0.74833 | 2456 | ||
| Synonymous | -0.0157 | 228 | 228 | 1.00 | 0.0000142 | 1845 |
| Loss of Function | 4.62 | 13 | 47.3 | 0.275 | 0.00000221 | 519 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000361 | 0.000361 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000164 | 0.000163 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000106 | 0.000105 |
| Middle Eastern | 0.000164 | 0.000163 |
| South Asian | 0.000229 | 0.000229 |
| Other | 0.000327 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3- kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. 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. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. {ECO:0000269|PubMed:10403904, ECO:0000269|PubMed:11484958, ECO:0000269|PubMed:12364394, ECO:0000269|PubMed:12490074, ECO:0000269|PubMed:15507525, ECO:0000269|PubMed:15733062, ECO:0000269|PubMed:1656220, ECO:0000269|PubMed:18840707}.; FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:22673088}.;
- Disease
- DISEASE: Note=AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer.;
- Pathway
- miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Signal Transduction;VEGFA-VEGFR2 Pathway;EGFR1;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;Validated transcriptional targets of deltaNp63 isoforms
(Consensus)
Recessive Scores
- pRec
- 0.233
Intolerance Scores
- loftool
- 0.241
- rvis_EVS
- -0.95
- rvis_percentile_EVS
- 9.32
Haploinsufficiency Scores
- pHI
- 0.316
- hipred
- Y
- hipred_score
- 0.736
- ghis
- 0.586
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Axl
- Phenotype
- vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; liver/biliary system phenotype; normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype;
Gene ontology
- Biological process
- neuron migration;natural killer cell differentiation;positive regulation of cytokine-mediated signaling pathway;blood vessel remodeling;phagocytosis;inflammatory response;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;spermatogenesis;nervous system development;Wnt signaling pathway;cell migration;peptidyl-tyrosine phosphorylation;forebrain cell migration;platelet activation;animal organ regeneration;cellular response to extracellular stimulus;negative regulation of interferon-gamma production;negative regulation of tumor necrosis factor production;positive regulation of natural killer cell differentiation;secretion by cell;erythrocyte homeostasis;substrate adhesion-dependent cell spreading;cellular response to interferon-alpha;ovulation cycle;negative regulation of apoptotic process;apoptotic cell clearance;protein kinase B signaling;negative regulation of neuron apoptotic process;innate immune response;viral entry into host cell;vascular endothelial growth factor receptor signaling pathway;cell maturation;positive regulation of pinocytosis;negative regulation of lymphocyte activation;positive regulation of protein kinase B signaling;vagina development;cellular response to hydrogen peroxide;cellular response to lipopolysaccharide;dendritic cell differentiation;neutrophil clearance;negative regulation of dendritic cell apoptotic process
- Cellular component
- extracellular space;plasma membrane;integral component of plasma membrane;cell surface;receptor complex;host cell surface;extracellular exosome
- Molecular function
- virus receptor activity;phosphatidylserine binding;protein tyrosine kinase activity;transmembrane receptor protein tyrosine kinase activity;protein binding;ATP binding;Wnt-protein binding;myosin heavy chain binding;phosphatidylinositol 3-kinase binding;protein heterodimerization activity