ALKBH1
protein-codingalkB homolog 1, histone H2A dioxygenase, the group of Alkylation repair homologs
Gene summary
This gene encodes a homolog to the E. coli alkB gene product. The E. coli alkB protein is part of the adaptive response mechanism of DNA alkylation damage repair. It is involved in damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine. [provided by RefSeq, Jul 2008]
Previous symbols:
- ALKBH
MANE transcript
NM_006020.3
Inheritance
—
ClinVar variants
U:53B:2
Top phenotype
—
gnomAD constraint
pLI —, LoF o/e 0.62
Max pathogenic AF
—
Genomic locus
chr14:77,672,404-77,708,023
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~35.6 kbLoading mutation effect viewer...
GenCC 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 ALKBH1 variants in ClinVar
not specifiedTotal: 53
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006020.3. 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 | 51 | 2 | 53 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 53 | 2 | 0 | 55 |
Loading ClinVar variants...
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
Showing 4 of 16 transcripts
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006011.2 | 6 | MANE Select | |
| Ensembl | ENSP00000216489.3 | 6 | MANE Select | |
| Ensembl | ENSP00000451386.1 | 3 | Standard | |
| Ensembl | ENSP00000451886.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- in utero embryonic development
- neuron migration
- placenta development
- tRNA wobble cytosine modification
- DNA repair
Molecular Function
- tRNA binding
- ferrous iron binding
- 2-oxoglutarate-dependent dioxygenase activity
- oxidative DNA demethylase activity
- chemoattractant activity
Cellular Component
- nuclear euchromatin
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216489
- Coding exons
- 6
- Length
- 35617
- Individuals with no LoFs
- 125643
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 104
- Defined
- 125747
- p
- 0.000414
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0535 | 227 | 229 | 0.990 | 0.0000124 | 2546 |
| Missense (PolyPhen) | 74 | 90.017 | 0.82207 | 1034 | ||
| Synonymous | 0.859 | 78 | 88.3 | 0.884 | 0.00000486 | 767 |
| Loss of Function | 1.48 | 11 | 17.7 | 0.620 | 0.00000101 | 190 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.000092 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0025 | 0.0025 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00035 | 0.00035 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dioxygenase that acts as on nucleic acids, such as DNA and tRNA (PubMed:18603530, PubMed:27745969, PubMed:27497299). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:18603530, PubMed:27497299). A number of activities have been described for this dioxygenase, but recent results suggest that it mainly acts as on tRNAs and mediates their demethylation or oxidation depending on the context and subcellular compartment (PubMed:27745969, PubMed:27497299). Mainly acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs, with a preference for N(1)-methyladenine at position 58 (m1A58) present on a stem loop structure of tRNAs (PubMed:27745969). Acts as a regulator of translation initiation and elongation in response to glucose deprivation: regulates both translation initiation, by mediating demethylation of tRNA(Met), and translation elongation, N(1)-methyladenine-containing tRNAs being preferentially recruited to polysomes to promote translation elongation (PubMed:27745969). In mitochondrion, specifically interacts with mt-tRNA(Met) and mediates oxidation of mt-tRNA(Met) methylated at cytosine(34) to form 5-formylcytosine (f(5)c) at this position (PubMed:27497299). mt-tRNA(Met) containing the f(5)c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation (PubMed:27497299). Specifically demethylates DNA methylated on the 6th position of adenine (N(6)- methyladenosine) DNA (PubMed:30017583). N(6)-methyladenosine (m6A) DNA is present at some L1 elements in embryonic stem cells and probably promotes their silencing (By similarity). Also able to repair alkylated single-stranded DNA and RNA containing 3- methylcytosine by oxidative demethylation, but with low activity (PubMed:18603530). Also has DNA lyase activity and introduces double-stranded breaks at abasic sites: cleaves both single- stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites (PubMed:19959401). DNA lyase activity does not require alpha-ketboglutarate and iron and leads to the formation of an irreversible covalent protein-DNA adduct with the 5' DNA product (PubMed:19959401, PubMed:23577621). DNA lyase activity is not required during base excision repair and class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation. May play a role in placental trophoblast lineage differentiation (By similarity). {ECO:0000250|UniProtKB:P0CB42, ECO:0000269|PubMed:18603530, ECO:0000269|PubMed:19959401, ECO:0000269|PubMed:23577621, ECO:0000269|PubMed:27497299, ECO:0000269|PubMed:27745969, ECO:0000269|PubMed:30017583}.;
Recessive Scores
- pRec
- 0.0831
Intolerance Scores
- LoFtool
- 0.750
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.982
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |