AXL

AXL receptor tyrosine kinase, the group of Fibronectin type III domain containing|V-set domain containing|Receptor tyrosine kinases

Basic information

Region (hg38): 19:41219222-41261766

Links

ENSG00000167601 ∙ NCBI:558 ∙ OMIM:109135 ∙ HGNC:905 ∙ Uniprot:P30530 ∙ 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 AXL gene.

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.

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			2	27	8	37
missense			62	13	3	78
nonsense						0
start loss			2			2
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	13	1	17
non coding			1	19	42	62
Total	0	0	69	59	53

Variants in AXL

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

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

Position	Type	Phenotype	Significance	ClinVar
19-41219366-A-G			Benign (Nov 10, 2018)
19-41219394-T-G			Uncertain significance (Jul 10, 2023)
19-41219397-C-T			Uncertain significance (Apr 25, 2023)
19-41219403-G-A		not specified	Uncertain significance (Aug 02, 2021)
19-41219428-G-A		AXL-related disorder	Likely benign (Dec 09, 2019)
19-41219445-C-T			Likely benign (May 14, 2018)
19-41219446-G-C			Likely benign (Jul 17, 2022)
19-41219471-C-T		not specified	Uncertain significance (Mar 19, 2024)
19-41219472-C-T		not specified	Uncertain significance (May 30, 2023)
19-41219505-G-A			Benign (Jun 19, 2021)
19-41220549-G-A			Benign (Jun 19, 2021)
19-41220623-A-C			Likely benign (Aug 17, 2023)
19-41220632-C-G			Likely benign (Dec 31, 2019)
19-41220640-G-A		AXL-related disorder	Likely benign (Jan 13, 2023)
19-41220662-G-A		not specified	Uncertain significance (Oct 26, 2022)
19-41220680-A-G		not specified	Uncertain significance (May 16, 2022)
19-41220692-C-T		not specified	Uncertain significance (Oct 06, 2021)
19-41220693-G-C		not specified	Uncertain significance (Oct 18, 2021)
19-41220698-C-T			Likely benign (Oct 04, 2022)
19-41220703-G-A			Likely benign (Sep 07, 2022)
19-41220710-C-A		not specified	Uncertain significance (Aug 13, 2021)
19-41220722-C-G			Uncertain significance (Sep 01, 2022)
19-41220728-G-A			Uncertain significance (Aug 01, 2023)
19-41220762-G-A			Uncertain significance (Nov 21, 2021)
19-41220786-C-T		not specified	Conflicting classifications of pathogenicity (Dec 14, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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