ALKBH4
protein-codingalkB homolog 4, lysine demethylase, the group of Alkylation repair homologs
Gene summary
Enables 2-oxoglutarate-dependent dioxygenase activity and actin binding activity. Involved in actomyosin structure organization and cleavage furrow ingression. Located in contractile ring and midbody. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.6 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 ALKBH4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017621.4. 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 | 1 | 1 | 2 | |||
| missense | 68 | 4 | 72 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 71 | 5 | 0 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060091.1 | 3 | MANE Select | |
| Ensembl | ENSP00000292566.3 | 3 | MANE Select | |
| Ensembl | ENSP00000420362.1 | 2 | Standard | |
| Ensembl | ENSP00000551870.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein demethylation
- actomyosin structure organization
- cleavage furrow ingression
- oxidation-reduction process
- oxidative demethylation
Molecular Function
- actin binding
- protein binding
- oxidoreductase activity
- 2-oxoglutarate-dependent dioxygenase activity
- demethylase activity
Cellular Component
- nucleus
- cytoplasm
- midbody
- contractile ring
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000292566
- Coding exons
- 3
- Length
- 8639
- Individuals with no LoFs
- 124835
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 124841
- p
- 0.0000240
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.562 | 181 | 204 | 0.889 | 0.0000143 | 1890 |
| Missense (PolyPhen) | 57 | 63.731 | 0.89438 | 610 | ||
| Synonymous | -1.11 | 106 | 92.4 | 1.15 | 0.00000661 | 657 |
| Loss of Function | 1.99 | 3 | 9.66 | 0.310 | 4.13e-7 | 107 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000060 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000021 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dioxygenase that mediates demethylation of actin monomethylated at 'Lys-84' (K84me1), thereby acting as a regulator of actomyosin-processes. Demethylation of actin K84me1 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. May be involved in transcription regulation. {ECO:0000269|PubMed:21166655, ECO:0000269|PubMed:23673617}.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.201
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.35
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.385
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |