ADCK5

Chr 8

aarF domain containing kinase 5

NCBI Gene: 203054 ENSG00000173137 UniProt: Q3MIX3 OMIM: 621165

ADCK5 encodes a predicted protein serine/threonine kinase localized to mitochondria, though its specific function and substrates remain unclear. Mutations cause autosomal recessive cerebellar ataxia, spasticity, and intellectual disability syndrome, typically presenting in childhood. The gene shows moderate constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable protein serine/threonine kinase activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.004

Z-score 3.18

OE 0.34 (0.20–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.18Z-score

OE missense 0.68 (0.61–0.76)

250 obs / 367.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.34 (0.20–0.59)

0≤0.351.4

Missense OE?0.68 (0.61–0.76)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 9 / 26.7Missense obs/exp: 250 / 367.6Syn Z: -0.14

Background carrier burden — how many people carry a rare variant somewhere in ADCK5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

810 rare PASS variants

Rare truncating (LoF)

1 in 2,600

113 rare PASS variants

Rare synonymous (reference)

1 in 120

458 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADCK5. 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 120	1 in 2,800
South Asian	~43k	1 in 64	1 in 3,200
Remaining (unassigned)	~30k	1 in 65	1 in 2,800
European (Finnish)	~27k	1 in 120	1 in 2,400
Admixed American	~22k	1 in 83	1 in 2,000
African / African American	~21k	1 in 78	1 in 3,200
East Asian	~20k	1 in 95	1 in 3,900
Ashkenazi Jewish	~13k	1 in 480	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 92	≈ 1 in 2,900

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): 13 of 15 coding exons well covered in gnomAD exomes; exons 1, 12 marginal. Genomes: 14 of 15 (exon 9 below).? see exons ↓