ALKBH5

Chr 17

alkB homolog 5, RNA demethylase

Also known as: ABH5, OFOXD, OFOXD1

NCBI Gene: 54890ENSG00000091542UniProt: Q6P6C2OMIM: 613303

The ALKBH5 protein is a dioxygenase that specifically removes N6-methyladenosine (m6A) modifications from RNA, thereby regulating mRNA processing, translation, and export. Mutations in this gene cause autosomal recessive intellectual disability with delayed speech and language development. This gene is highly constrained against loss-of-function variants (pLI 0.95, LOEUF 0.34), suggesting that complete loss of protein function is poorly tolerated.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.34
Clinical Summary— ALKBH5
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
116 unique Pathogenic / Likely Pathogenic· 43 VUS of 172 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.950
Z-score 3.20
OE 0.07 (0.03–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.56Z-score
OE missense 0.54 (0.47–0.62)
131 obs / 243.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.03–0.34)
0≤0.351.4
Missense OE0.54 (0.47–0.62)
0≤0.61.4
Synonymous OE1.51
0≤1.21.6
LoF obs/exp: 1 / 13.8Missense obs/exp: 131 / 243.5Syn Z: -3.97
DN
0.2199th %ile
GOF
0.2796th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.34

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

172 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116
VUS43
Likely Benign3
116
Pathogenic
43
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
116
0
116
Likely Pathogenic
0
0
0
0
0
VUS
0
39
4
0
43
Likely Benign
0
0
1
2
3
Benign
0
0
0
0
0
Total0391212162

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ALKBH5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
M6A demethylase ALKBH5 mediated Igfbp4 mRNA m6A modification drives fibroblast activation and pathological upper airway fibrosis.
Wang J et al.·Clin Transl Med
2026
ALKBH5/IGF2BP1-mediated m6A demethylation of TRIM37 promotes pancreatic cancer tumorigenesis and glycolysis by mediating RBMX degradation.
Yan C et al.·Cell Biol Toxicol
2026
Tamoxifen differentially modulates endometrial hyperplasia via wild-type and mutant p53 regulation of the ALKBH5-REG1A axis.
Wang R et al.·Front Oncol
2026Open Access
HIV-1 Vpr activates microglia by upregulating m6A modification through ubiquitin-proteasome pathway-mediated degradation of the demethylase ALKBH5.
Peng Q et al.·Virulence
2026Open Access
Regulatory mechanisms of ALKBH5/CIITA axis in the synergistic modulation of hepatocellular carcinoma radiotherapy and immunotherapy.
Wang F et al.·Genes Immun
2026Functional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients