ALKBH2
protein-codingalkB homolog 2, alpha-ketoglutarate dependent dioxygenase, the group of Alkylation repair homologs
Gene summary
The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the specific DNA lesions generated in single-stranded DNA. ALKBH2 and ALKBH3 (MIM 610603) are E. coli AlkB homologs that catalyze the removal of 1-methyladenine and 3-methylcytosine (Duncan et al., 2002 [PubMed 12486230]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.4 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 ALKBH2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001145374.2. 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 | 6 | 7 | |||
| missense | 36 | 3 | 39 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 9 | 0 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001138846.1 | 3 | MANE Select | |
| Ensembl | ENSP00000398181.1 | 3 | MANE Select | |
| RefSeq | NP_001001655.1 | 3 | Standard | |
| RefSeq | NP_001138847.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DNA Repair
- ALKBH2 mediated reversal of alkylation damage
- Reversal of alkylation damage by DNA dioxygenases
- DNA Damage Reversal
Biological Process
- DNA dealkylation involved in DNA repair
- oxidative DNA demethylation
- oxidative demethylation
- DNA demethylation
Molecular Function
- ferrous iron binding
- DNA-N1-methyladenine dioxygenase activity
- cytosine C-5 DNA demethylase activity
- 1-ethyladenine demethylase activity
Cellular Component
- nucleus
- nucleoplasm
- microtubule cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000429722
- Coding exons
- 3
- Length
- 5441
- Individuals with no LoFs
- 125679
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 69
- Defined
- 125748
- p
- 0.000274
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.362 | 142 | 155 | 0.918 | 0.00000928 | 1693 |
| Missense (PolyPhen) | 50 | 52.226 | 0.95737 | 597 | ||
| Synonymous | -0.0113 | 63 | 62.9 | 1.00 | 0.00000386 | 542 |
| Loss of Function | 1.18 | 5 | 8.76 | 0.570 | 4.55e-7 | 105 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.0015 | 0.0015 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00075 | 0.00075 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1- ethenoadenine (in vitro). Has strong preference for double- stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. {ECO:0000269|PubMed:12486230, ECO:0000269|PubMed:12594517, ECO:0000269|PubMed:16174769, ECO:0000269|PubMed:18432238, ECO:0000269|PubMed:18519673}.;
Recessive Scores
- pRec
- 0.146
Intolerance Scores
- LoFtool
- 0.870
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 75.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.662
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |