GeneBe

ALKBH5

protein-coding

alkB homolog 5, RNA demethylase, the group of Alkylation repair homologs

Gene summary

Enables mRNA N6-methyladenosine dioxygenase activity and molecular condensate scaffold activity. Involved in membraneless organelle assembly; post-transcriptional regulation of gene expression; and response to hypoxia. Acts upstream of or within regulation of mRNA export from nucleus and regulation of mRNA processing. Located in nuclear speck. Is active in paraspeckles. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:
  • OFOXD1

MANE transcript

NM_017758.4

Inheritance

—

ClinVar variants

U:40B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr17:18,183,078-18,209,954

External References & Databases

Ensembl (ENSG00000091542)NCBI Gene (54890)OMIM (613303)HGNC:25996GenCCUniProt (Q6P6C2)AlphaFoldClinVar (ALKBH5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~26.9 kb
Loading 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 ALKBH5 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 40
not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017758.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
 2
missense
40
clinvar
 40
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00402042
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_017758.4RefSeqNP_060228.34MANE Select
ENST00000399138.5EnsemblENSP00000382091.44MANE Select
ENST00000541285.1EnsemblENSP00000468116.11Standard
ENST00000541285.2EnsemblENSP00000468116.11Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • DNA Repair
  • Reversal of alkylation damage by DNA dioxygenases
  • DNA Damage Reversal

Biological Process

  • response to hypoxia
  • DNA dealkylation involved in DNA repair
  • mRNA processing
  • mRNA export from nucleus
  • spermatogenesis

Molecular Function

  • RNA binding
  • 2-oxoglutarate-dependent dioxygenase activity
  • oxidative RNA demethylase activity
  • metal ion binding
  • RNA N6-methyladenosine dioxygenase activity

Cellular Component

  • nucleus
  • nucleoplasm
  • Golgi apparatus
  • cytosol
  • nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000399138
Coding exons
4
Length
26877
Individuals with no LoFs
124786
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
124789
p
0.0000120
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.561312440.5380.00001372526
Missense (PolyPhen)28109.040.256791014
Synonymous-3.9714696.41.510.00000482819
Loss of Function3.20113.80.07246.73e-7166

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:23177736, PubMed:24778178, PubMed:24616105, PubMed:24489119). Can also demethylate N(6)- methyladenosine in single-stranded DNA (in vitro) (PubMed:24616105). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:21264265, PubMed:23177736, PubMed:24778178, PubMed:24616105, PubMed:24489119). Demethylation of m6A mRNA affects mRNA processing and export (PubMed:23177736). Required for spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q3TSG4, ECO:0000269|PubMed:21264265, ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:24489119, ECO:0000269|PubMed:24616105, ECO:0000269|PubMed:24778178}.;

Intolerance Scores

LoFtool
0.0348
RVIS EVS
-0.41
RVIS percentile EVS
26.23

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.234

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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