ALKBH5

Chr 17

alkB homolog 5, RNA demethylase

Also known as: ABH5, OFOXD, OFOXD1

NCBI Gene: 54890ENSG00000091542UniProt: Q6P6C2

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 Golgi apparatus; cytosol; and nuclear speck. Is active in paraspeckles. [provided by Alliance of Genome Resources, Jul 2025]

162
ClinVar variants
116
Pathogenic / LP
0.95
pLI score· haploinsufficient
0
Active trials
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 Pathogenic / Likely Pathogenic· 43 VUS of 162 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.47–0.62)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.51
0≤1.21.6
LoF obs/exp: 1 / 13.8Missense obs/exp: 131 / 243.5Syn Z: -3.97

ClinVar Variant Classifications

162 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice.
Zhuang T et al.·Nat Commun
2024
Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification.
Hu Y et al.·Mol Cancer
2022
ALKBH5 Drives Immune Suppression Via Targeting AXIN2 to Promote Colorectal Cancer and Is a Target for Boosting Immunotherapy.
Zhai J et al.·Gastroenterology
2023
LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling.
Luo F et al.·Mol Cancer
2024
UBR7 inhibits HCC tumorigenesis by targeting Keap1/Nrf2/Bach1/HK2 and glycolysis.
Zhao L et al.·J Exp Clin Cancer Res
2022
Suxiao Jiuxin Pill alleviates myocardial ischemia/reperfusion-induced autophagy via miR-193a-3p/ALKBH5 pathway.
Wang D et al.·Phytomedicine
2024
ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages.
Hua X et al.·J Exp Clin Cancer Res
2024
Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases.
Li Y et al.·Nat Commun
2025
ALKBH5 Regulates Macrophage Senescence and Accelerates Atherosclerosis by Promoting CCL5 m(6)A Modification.
Gao R et al.·Arterioscler Thromb Vasc Biol
2025
ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression.
You Y et al.·Int J Biol Sci
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools