ALKBH8

Chr 11

alkB homolog 8, tRNA methyltransferase

Also known as: ABH8, MRT71, TRM9, TRMT9, TRMT9A

NCBI Gene: 91801 ENSG00000137760 UniProt: Q96BT7

Enables tRNA (uridine) methyltransferase activity; tRNA binding activity; and zinc ion binding activity. Involved in DNA damage response; tRNA methylation; and tRNA wobble uridine modification. Located in cytosol and nucleoplasm. Implicated in autosomal recessive intellectual developmental disorder 71. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal recessive 71

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.000

Z-score 2.90

OE 0.40 (0.25–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.85Z-score

OE missense 0.87 (0.79–0.96)

290 obs / 333.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.25–0.67)

0≤0.351.4

Missense OE?0.87 (0.79–0.96)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 11 / 27.3Missense obs/exp: 290 / 333.9Syn Z: 0.71

Background carrier burden — how many people carry a rare variant somewhere in ALKBH8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

833 rare PASS variants

Rare truncating (LoF)

1 in 950

136 rare PASS variants

Rare synonymous (reference)

1 in 87

291 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ALKBH8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 86	1 in 1,400
South Asian	~43k	1 in 47	1 in 830
Remaining (unassigned)	~30k	1 in 57	1 in 510
European (Finnish)	~27k	1 in 190	1 in 3,900
Admixed American	~22k	1 in 51	1 in 640
African / African American	~21k	1 in 48	1 in 930
East Asian	~20k	1 in 50	1 in 690
Ashkenazi Jewish	~13k	1 in 300	1 in 2,500
Middle Eastern	~2,883	1 in 84	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 11 coding exons well covered in gnomAD exomes; exons 6, 9 marginal. Genomes: all 11.? see exons ↓