AK3

Chr 9

adenylate kinase 4

Also known as: AK 4, AK3, AK3L1, AK3L2

NCBI Gene: 205ENSG00000147853UniProt: P27144

This gene encodes a member of the adenylate kinase family of enzymes. The encoded protein is localized to the mitochondrial matrix. Adenylate kinases regulate the adenine and guanine nucleotide compositions within a cell by catalyzing the reversible transfer of phosphate group among these nucleotides. Five isozymes of adenylate kinase have been identified in vertebrates. Expression of these isozymes is tissue-specific and developmentally regulated. A pseudogene for this gene has been located on chromosome 17. Three transcript variants encoding the same protein have been identified for this gene. Sequence alignment suggests that the gene defined by NM_013410, NM_203464, and NM_001005353 is located on chromosome 1. [provided by RefSeq, Jul 2008]

237
ClinVar variants
167
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— AK3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
167 Pathogenic / Likely Pathogenic· 60 VUS of 237 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.97Z-score
OE missense 1.50 (1.33–1.69)
185 obs / 123.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.42–1.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.50 (1.33–1.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.28
0≤1.21.6
LoF obs/exp: 7 / 9.4Missense obs/exp: 185 / 123.5Syn Z: -1.55

ClinVar Variant Classifications

237 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic160
Likely Pathogenic7
VUS60
Likely Benign1
Benign2
160
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
160
0
160
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
Total0451850230

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ADENYLATE KINASE 3; AK3
MIM #609290 · *
Clinical Literature
Landmark / reviewRecent case evidence
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
Neutrophil GM-CSF signaling in inflammatory bowel disease patients is influenced by non-coding genetic variants.
Venkateswaran S et al.·Sci Rep
2019Cohort
Identification of a novel glycolysis-related signature to predict the prognosis of patients with breast cancer.
He M et al.·World J Surg Oncol
2021Cohort
Candidate predisposing germline copy number variants in early onset colorectal cancer patients.
Brea-Fernandez AJ et al.·Clin Transl Oncol
2017Cohort
Integrative Placental Multi-Omics Analysis Reveals Perturbed Pathways and Potential Prognostic Biomarkers in Gestational Hypertension.
Varghese B et al.·Arch Med Res
2024
Identification and prognostic value of a glycolysis-related gene signature in patients with bladder cancer.
Wu Z et al.·Medicine (Baltimore)
2021Cohort
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
Development of a protein biochip to identify 6 monoclonal antibodies against subtypes of recombinant human interferons.
Xu Z et al.·Assay Drug Dev Technol
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet

External Resources

Links to major genomics databases and tools