AK3

Chr 9

adenylate kinase 3

Also known as: AK3L1, AK6, AKL3L, AKL3L1, FIX

NCBI Gene: 50808ENSG00000147853UniProt: P27144OMIM: 609290

The protein is a mitochondrial nucleoside phosphate kinase that maintains cellular nucleotide homeostasis by catalyzing phosphorylation reactions, particularly converting AMP to ADP using ATP or GTP as phosphate donors. Mutations cause autosomal recessive reticular dysgenesis, a severe combined immunodeficiency with sensorineural hearing loss that presents in early infancy. The gene shows very low constraint against loss-of-function variants (pLI 0.0001), consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.39
Clinical Summary— AK3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
168 unique Pathogenic / Likely Pathogenic· 60 VUS of 238 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
1.39LOEUF
pLI 0.000
Z-score 0.73
OE 0.74 (0.42–1.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.97Z-score
OE missense 1.50 (1.33–1.69)
185 obs / 123.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.74 (0.42–1.39)
0≤0.351.4
Missense OE1.50 (1.33–1.69)
0≤0.61.4
Synonymous OE1.28
0≤1.21.6
LoF obs/exp: 7 / 9.4Missense obs/exp: 185 / 123.5Syn Z: -1.55
DN
0.78top 25%
GOF
0.6345th %ile
LOF
0.2776th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

238 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic161
Likely Pathogenic7
VUS60
Likely Benign1
Benign2
161
Pathogenic
7
Likely Pathogenic
60
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
161
0
161
Likely Pathogenic
0
0
7
0
7
VUS
0
45
15
0
60
Likely Benign
0
0
1
0
1
Benign
0
0
2
0
2
Total0451860231

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

View in ClinVar →

Protein Context — Lollipop Plot

AK3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
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
Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.
Wang Y et al.·Genome Med
2025Cohort
20 years later: unravelling the genomic success of New Zealand's home-grown AK3 community-associated methicillin-resistant Staphylococcus aureus.
White RT et al.·Microb Genom
2025
Integrative Placental Multi-Omics Analysis Reveals Perturbed Pathways and Potential Prognostic Biomarkers in Gestational Hypertension.
Varghese B et al.·Arch Med Res
2024
The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy.
Spinetti G et al.·Aging (Albany NY)
2017
Characterisation of methicillin-resistant Staphylococcus aureus clinical isolates from animals in New Zealand, 2012-2013, and subclinical colonisation in dogs and cats in Auckland.
Karkaba A et al.·N Z Vet J
2017
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