AK1

Chr 9AR

adenylate kinase 1

Also known as: ADK, Adk1, CNSHA3, HTL-S-58j

NCBI Gene: 203ENSG00000106992UniProt: P00568OMIM: 103000

The protein catalyzes the reversible transfer of phosphate groups between ATP and AMP, maintaining cellular energy homeostasis and adenine nucleotide metabolism in skeletal muscle, brain, and erythrocytes. Mutations cause autosomal recessive congenital nonspherocytic hemolytic anemia type 3 through production of a functionally inadequate enzyme. The pathogenic mechanism involves loss of function, disrupting energy metabolism particularly in red blood cells.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.941 OMIM phenotype
Clinical Summary— AK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 46 VUS of 152 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
0.94LOEUF
pLI 0.027
Z-score 1.71
OE 0.41 (0.20–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.65Z-score
OE missense 0.83 (0.70–0.98)
96 obs / 115.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.20–0.94)
0≤0.351.4
Missense OE0.83 (0.70–0.98)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 4 / 9.8Missense obs/exp: 96 / 115.6Syn Z: 0.19
DN
0.81top 10%
GOF
0.5955th %ile
LOF
0.2189th %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

152 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic5
VUS46
Likely Benign33
Benign14
Conflicting2
47
Pathogenic
5
Likely Pathogenic
46
VUS
33
Likely Benign
14
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
6
40
0
47
Likely Pathogenic
3
1
1
0
5
VUS
0
43
3
0
46
Likely Benign
0
2
13
18
33
Benign
0
1
11
2
14
Conflicting
—2
Total4536820147

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

View in ClinVar →

Protein Context — Lollipop Plot

AK1 · 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 4 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