ABL2
protein-codingABL proto-oncogene 2, non-receptor tyrosine kinase, the group of Abl family tyrosine kinases|SH2 domain containing
Gene summary
This gene encodes a member of the Abelson family of nonreceptor tyrosine protein kinases. The protein is highly similar to the c-abl oncogene 1 protein, including the tyrosine kinase, SH2 and SH3 domains, and it plays a role in cytoskeletal rearrangements through its C-terminal F-actin- and microtubule-binding sequences. This gene is expressed in both normal and tumor cells, and is involved in translocation with the ets variant 6 gene in leukemia. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Nov 2009]
- ABLL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~130.4 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 ABL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007314.4. 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 | 1 | 1 | 2 | |||
| missense | 119 | 1 | 1 | 121 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 128 | 2 | 1 | 131 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009298.1 | 12 | MANE Select | |
| Ensembl | ENSP00000427562.1 | 12 | MANE Select | |
| RefSeq | NP_001129472.1 | 13 | Standard | |
| RefSeq | NP_001129473.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Viral myocarditis - Homo sapiens (human)
- ErbB signaling pathway - Homo sapiens (human)
- Ras signaling pathway - Homo sapiens (human)
- Ras Signaling
- Developmental Biology
Biological Process
- cellular protein modification process
- cell adhesion
- signal transduction
- positive regulation of cytosolic calcium ion concentration
- regulation of autophagy
Molecular Function
- magnesium ion binding
- phosphotyrosine residue binding
- actin monomer binding
- protein kinase activity
- protein tyrosine kinase activity
Cellular Component
- cytosol
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000502732
- Coding exons
- 12
- Length
- 130358
- Individuals with no LoFs
- 125588
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 159
- Defined
- 125748
- p
- 0.000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.69 | 520 | 640 | 0.813 | 0.0000332 | 7645 |
| Missense (PolyPhen) | 172 | 287.27 | 0.59875 | 3486 | ||
| Synonymous | -0.813 | 265 | 249 | 1.07 | 0.0000134 | 2453 |
| Loss of Function | 3.94 | 20 | 50.1 | 0.399 | 0.00000321 | 550 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.00043 | 0.00038 | rare |
| Ashkenazi Jewish | 0.0030 | 0.0030 | notable |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.00072 | 0.00071 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Non-receptor tyrosine-protein kinase that plays an ABL1- overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin- bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. {ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}.;
Recessive Scores
- pRec
- 0.213
Intolerance Scores
- LoFtool
- 0.680
- RVIS EVS
- -0.99
- RVIS percentile EVS
- 8.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.984
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |