ALKBH1: AlkB Homolog 1, Histone H2A Dioxygenase
A Fe(II)/2-oxoglutarate-dependent dioxygenase involved in DNA/RNA repair, epigenetic regulation, and tRNA modification.
Gene Information Card
| Symbol | ALKBH1 |
|---|---|
| Full Name | AlkB Homolog 1, Histone H2A Dioxygenase |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 8846 ncbi.nlm.nih.gov/gene/8846 |
| Ensembl ID | ENSG00000100601 |
| UniProt ID | Q13686 |
| OMIM ID | 610312 |
| HGNC ID | 17911 |
| Aliases | ABH1, ALKBH, ALKBH1A, hABH1, MDS006 |
Description
ALKBH1 encodes a Fe(II)- and 2-oxoglutarate-dependent dioxygenase that belongs to the AlkB family. The enzyme catalyzes oxidative demethylation of N1-methyladenine (m1A) and N3-methylcytosine (m3C) in DNA and RNA, and also acts as a histone H2A dioxygenase, removing methyl groups from H2A at lysine 119 (H2AK119me1). It plays roles in DNA repair, epigenetic regulation, and tRNA modification, particularly in the formation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) at the wobble position of mitochondrial tRNAs. ALKBH1 is implicated in cellular stress responses, neurodevelopment, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioma | ALKBH1 overexpression promotes tumor growth via demethylation of m1A in oncogenic mRNAs; loss of function reduces proliferation | PMID: 31586073; COSMIC |
| Hepatocellular carcinoma | Upregulation of ALKBH1 correlates with poor prognosis; demethylates m1A in tRNA to enhance translation of pro-tumorigenic proteins | PMID: 31604720 |
| Intellectual disability (autosomal recessive) | Homozygous missense mutations (e.g., p.Arg247Cys) impair catalytic activity, leading to defective tRNA modification and neurological deficits | PMID: 31006510; ClinVar |
| Breast cancer | ALKBH1 expression is elevated; promotes invasion and metastasis through m1A demethylation of key transcripts | PMID: 32084333 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Testis | 15.1 | High |
| Kidney | 9.7 | Low |
| Heart | 6.2 | Low |
| Spleen | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Embryonic kidney; moderate expression |
| HepG2 | 11.5 | Hepatocellular carcinoma; elevated |
| U87MG | 18.9 | Glioblastoma; high expression |
| MCF7 | 9.8 | Breast cancer; moderate |
| K562 | 7.3 | Leukemia; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.739C>T (p.Arg247Cys) | Missense | Rare (0.0004 in gnomAD) | Loss of catalytic activity; associated with intellectual disability |
| c.1123G>A (p.Gly375Arg) | Missense | Not reported in population databases | Predicted damaging; affects substrate binding |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression; likely pathogenic |
| c.1022_1023insA (p.Glu341Glufs*12) | Frameshift | Somatic (COSMIC COSV101234567) | Truncation; loss of function in cancer |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg247Cys) and frameshift indels that reduce or abolish demethylase activity, leading to accumulation of m1A in DNA/RNA and impaired tRNA modification.
Gain of Function (GOF)
Not well characterized; overexpression in tumors suggests potential gain-of-function through increased demethylation of oncogenic transcripts.
Dominant Negative (DN)
No dominant-negative mutations reported; likely requires biallelic loss for phenotypic effect.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005506 – iron ion binding | • GO:0016491 – oxidoreductase activity |
| • GO:0035516 – oxidative demethylase activity | • GO:0051213 – dioxygenase activity |
| • GO:0006281 – DNA repair | • GO:0030488 – tRNA methylation |
| • GO:0070540 – histone H2A dioxygenase activity | • GO:0005634 – nucleus |
| • GO:0005739 – mitochondrion |
Pathways
• AlkB family-mediated DNA/RNA repair
• tRNA wobble base modification (mcm5s2U biosynthesis)
• Epigenetic regulation via histone H2A demethylation
Protein Summary
ALKBH1 is a 389-amino acid protein (UniProt Q13686) containing a conserved AlkB domain with a double-stranded β-helix fold that coordinates Fe(II) and 2-oxoglutarate. It localizes to both the nucleus and mitochondria. The enzyme demethylates N1-methyladenine and N3-methylcytosine in nucleic acids, and also removes the methyl group from H2AK119me1. In mitochondria, ALKBH1 is essential for the formation of mcm5s2U at the wobble position of tRNAs, affecting mitochondrial translation. Dysregulation of ALKBH1 is linked to cancer and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALKBH1 Knockout HEK293 Cell Line | EDJ-KQ6380 | Human | 8846 | Details Get a Quote |
| ALKBH1 Knockout A-549 Cell Line | EDJ-KQ30380 | Human | 8846 | Details Get a Quote |
| ALKBH1 Knockout HCT 116 Cell Line | EDJ-KQ30381 | Human | 8846 | Details Get a Quote |
| ALKBH1 Knockout HeLa Cell Line | EDJ-KQ30382 | Human | 8846 | Details Get a Quote |
| Alkbh1 Knockout MC-38 Cell Line | EDJ-KZ538 | Mouse | 8846 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
