ANKRD16

Chr 10

ankyrin repeat domain 16

NCBI Gene: 54522 ENSG00000134461 UniProt: Q6P6B7 OMIM: 618017

ANKRD16 encodes a protein that ensures translational fidelity by preventing serine misincorporation into proteins through its interaction with alanyl-tRNA synthetase and promotion of serine-mischarged tRNA(Ala) hydrolysis. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in tRNA modification. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.000

Z-score 0.38

OE 0.90 (0.60–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 0.99 (0.88–1.12)

192 obs / 193.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.90 (0.60–1.39)

0≤0.351.4

Missense OE?0.99 (0.88–1.12)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 15 / 16.7Missense obs/exp: 192 / 193.6Syn Z: -0.12

Background carrier burden — how many people carry a rare variant somewhere in ANKRD16?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

537 rare PASS variants

Rare truncating (LoF)

1 in 1,000

106 rare PASS variants

Rare synonymous (reference)

1 in 320

208 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANKRD16. 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 110	1 in 1,000
South Asian	~43k	1 in 76	1 in 1,600
Remaining (unassigned)	~30k	1 in 72	1 in 1,100
European (Finnish)	~27k	1 in 320	1 in 4,200
Admixed American	~22k	1 in 90	1 in 960
African / African American	~21k	1 in 86	1 in 1,000
East Asian	~20k	1 in 110	1 in 540
Ashkenazi Jewish	~13k	1 in 480	none seen
Middle Eastern	~2,884	1 in 74	≈ 1 in 710

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): 5 of 7 coding exons well covered in gnomAD exomes; exons 1, 6 marginal. Genomes: all 7.? see exons ↓