AK8

Chr 9

adenylate kinase 8

Also known as: AK 8, C9orf98

NCBI Gene: 158067ENSG00000165695UniProt: Q96MA6OMIM: 615365

Adenylate kinase 8 catalyzes the reversible transfer of phosphate groups between nucleoside triphosphates and monophosphates, with highest activity toward AMP, and is located in motile cilia where it contributes to ventricular system development. Mutations cause autosomal recessive ciliary dyskinesia with cerebral ventricular dilatation, affecting both respiratory and neurological systems. The gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.19
Clinical Summary— AK8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 83 VUS of 134 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.19LOEUF
pLI 0.000
Z-score 0.85
OE 0.81 (0.56–1.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.71Z-score
OE missense 0.88 (0.79–0.98)
240 obs / 273.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.81 (0.56–1.19)
0≤0.351.4
Missense OE0.88 (0.79–0.98)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 19 / 23.4Missense obs/exp: 240 / 273.2Syn Z: 0.13
DN
0.6455th %ile
GOF
0.6248th %ile
LOF
0.3161th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

134 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic1
VUS83
Likely Benign4
38
Pathogenic
1
Likely Pathogenic
83
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
38
0
38
Likely Pathogenic
0
0
1
0
1
VUS
0
71
12
0
83
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total075510126

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

View in ClinVar →

Protein Context — Lollipop Plot

AK8 · 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
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