AK2 - dismech genes

Normal function · from ai-gene-review (P54819, commit 79fe13b38970) · AI-generated, not KB evidence

AK2 is a mitochondrial intermembrane-space adenylate kinase that reversibly transfers a phosphate between ATP and AMP to form two ADP molecules. This reaction balances adenine nucleotides and supplies ADP without hydrolyzing ATP to free phosphate. Human AK2A and AK2B are catalytically active isoforms. Biallelic deficiency causes reticular dysgenesis, with severe myeloid and lymphoid defects and sensorineural deafness. Human hematopoietic studies connect the differentiation defect to disrupted nucleotide and metabolic homeostasis. AK2 also binds DUSP26 and increases its protein-phosphatase activity independently of adenylate-kinase catalysis.

Catalyzes reversible phosphate transfer between ATP and AMP, forming two ADP molecules in the forward direction and ATP plus AMP in the reverse direction. The mitochondrial intermembrane-space enzyme thereby balances adenine nucleotides; ATP binding, AMP/ATP metabolism and ADP formation are aspects of this single catalytic unit. Both tested human AK2A and AK2B are active. The compartment assignment includes conserved mammalian localization evidence, whereas human enzyme purification directly establishes catalysis.

molecular function: AMP kinase activity · directly involved in: nucleobase-containing small molecule interconversion; ADP biosynthetic process · locations: mitochondrial intermembrane space

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Reticular Dysgenesis	causative germline loss of function	mechanism: AK2 Loss of Function in the Mitochondrial Intermembrane Space animal model: ak2 mutant and morphant zebrafish
Severe Combined Immunodeficiency	untyped Causative	mechanism: Defective haematopoietic precursor survival subtype: Reticular dysgenesis scoped to subtype: Reticular dysgenesis

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
reticular dysgenesis MONDO:0009973	AR	Definitive 2021-05-20	Reticular Dysgenesis causative