ALKBH1
alkB homolog 1, histone H2A dioxygenase, the group of Alkylation repair homologs
Basic information
Region (hg38): 14:77672404-77708023
Previous symbols: [ "ALKBH" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (47 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALKBH1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006020.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 46 | 47 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 46 | 1 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ALKBH1 | protein_coding | protein_coding | ENST00000216489 | 6 | 35617 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00000490 | 0.868 | 125643 | 0 | 104 | 125747 | 0.000414 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0535 | 227 | 229 | 0.990 | 0.0000124 | 2546 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000522 | 0.000522 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00250 | 0.00250 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000353 | 0.000352 |
| Middle Eastern | 0.00250 | 0.00250 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.000326 | 0.000326 |
dbNSFP
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
Haploinsufficiency Scores
- pHI
- 0.0857
- hipred
- N
- hipred_score
- 0.174
- ghis
- 0.475
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.982
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Alkbh1
- Phenotype
- cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; embryo phenotype; skeleton phenotype; limbs/digits/tail 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); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive 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);
Gene ontology
- Biological process
- in utero embryonic development;neuron migration;placenta development;tRNA wobble cytosine modification;DNA repair;DNA dealkylation involved in DNA repair;regulation of translational initiation;regulation of translational elongation;neuron projection development;oxidative DNA demethylation;RNA repair;negative regulation of neuron apoptotic process;developmental growth;positive chemotaxis;regulation of mitochondrial translation;oxidative demethylation;DNA demethylation;tRNA demethylation
- Cellular component
- nuclear euchromatin;mitochondrion
- Molecular function
- tRNA binding;ferrous iron binding;2-oxoglutarate-dependent dioxygenase activity;oxidative DNA demethylase activity;chemoattractant activity;dioxygenase activity;methylcytosine dioxygenase activity;1-ethyladenine demethylase activity;class I DNA-(apurinic or apyrimidinic site) endonuclease activity;tRNA demethylase activity