AK1

Chr 9AR

adenylate kinase 1

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

NCBI Gene: 203 ENSG00000106992 UniProt: P00568 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes an adenylate kinase enzyme involved in energy metabolism and homeostasis of cellular adenine nucleotide ratios in different intracellular compartments. This gene is highly expressed in skeletal muscle, brain and erythrocytes. Certain mutations in this gene resulting in a functionally inadequate enzyme are associated with a rare genetic disorder causing nonspherocytic hemolytic anemia. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene shares readthrough transcripts with the upstream ST6GALNAC6 gene. [provided by RefSeq, Jan 2022]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Anemia, congenital, nonspherocytic hemolytic, 3, adenylate kinase deficientMIM #612631

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Anemia, congenital, nonspherocytic hemolytic, 3, adenylate kinase deficient; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

Mechanism· predicted

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 OE?0.41 (0.20–0.94)

0≤0.351.4

Missense OE?0.83 (0.70–0.98)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 4 / 9.8Missense obs/exp: 96 / 115.6Syn Z: 0.19

Background carrier burden — how many people carry a rare variant somewhere in AK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

250 rare PASS variants

Rare truncating (LoF)

1 in 6,700

33 rare PASS variants

Rare synonymous (reference)

1 in 210

114 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AK1. 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 230	1 in 9,900
South Asian	~43k	1 in 170	1 in 8,500
Remaining (unassigned)	~30k	1 in 260	1 in 5,000
European (Finnish)	~27k	1 in 640	≈ 1 in 8,900
Admixed American	~22k	1 in 150	≈ 1 in 4,500
African / African American	~21k	1 in 180	1 in 3,000
East Asian	~20k	1 in 320	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 1,400	none seen
Middle Eastern	~2,884	1 in 240	none seen

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓