ALKBH3
protein-codingalkB homolog 3, 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 (MIM 610602) and ALKBH3 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 ~39.5 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 ALKBH3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_139178.4. 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 | 0 | |||||
| missense | 53 | 53 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 58 | 0 | 0 | 58 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_631917.1 | 9 | MANE Select | |
| Ensembl | ENSP00000302232.4 | 9 | MANE Select | |
| Ensembl | ENSP00000434229.1 | 2 | Standard | |
| Ensembl | ENSP00000435848.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DNA Repair
- ALKBH3 mediated reversal of alkylation damage
- Reversal of alkylation damage by DNA dioxygenases
- DNA Damage Reversal
Biological Process
- DNA repair
- DNA dealkylation involved in DNA repair
- cell population proliferation
- oxidative single-stranded DNA demethylation
- oxidative single-stranded RNA demethylation
Molecular Function
- protein binding
- ferrous iron binding
- L-ascorbic acid binding
- DNA-N1-methyladenine dioxygenase activity
- cytosine C-5 DNA demethylase activity
Cellular Component
- nucleus
- nucleoplasm
- mitochondrion
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302708
- Coding exons
- 9
- Length
- 39456
- Individuals with no LoFs
- 125350
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 398
- Defined
- 125748
- p
- 0.00158
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0845 | 160 | 163 | 0.981 | 0.00000876 | 1857 |
| Missense (PolyPhen) | 66 | 67.352 | 0.97993 | 783 | ||
| Synonymous | -0.00298 | 53 | 53.0 | 1.00 | 0.00000259 | 539 |
| Loss of Function | 0.414 | 19 | 21.1 | 0.903 | 0.00000132 | 209 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0011 | notable |
| Latino/Admixed American | 0.00064 | 0.00064 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00097 | 0.00097 | rare |
| European (Non-Finnish) | 0.0027 | 0.0027 | notable |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.0015 | 0.0015 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A) (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:26863196, PubMed:26863410). Repairs alkylated DNA containing 1- methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:25944111). Has a strong preference for single-stranded DNA (PubMed:12486230, PubMed:12594517, PubMed:16174769). Able to process alkylated m3C within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3 (PubMed:22055184). Also acts on RNA (PubMed:12594517, PubMed:16174769, PubMed:26863196, PubMed:26863410, PubMed:16858410). Demethylates N(1)-methyladenosine (m1A) RNA, an epigenetic internal modification of messenger RNAs (mRNAs) highly enriched within 5'- untranslated regions (UTRs) and in the vicinity of start codons (PubMed:26863196, PubMed:26863410). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:22055184, PubMed:16858410). {ECO:0000269|PubMed:12486230, ECO:0000269|PubMed:12594517, ECO:0000269|PubMed:16174769, ECO:0000269|PubMed:16858410, ECO:0000269|PubMed:22055184, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26863196, ECO:0000269|PubMed:26863410}.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.885
- RVIS EVS
- 0.4
- RVIS percentile EVS
- 76.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.551
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |