AK2 Gene: Adenylate Kinase 2 - Function, Disease Associations, and Clinical Significance
Comprehensive guide to the AK2 gene, including genomic information, expression patterns, mutations, and associated disorders.
Gene Information Card
| Symbol | AK2 |
|---|---|
| Full Name | Adenylate Kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p35.1 |
| NCBI Gene ID | 204 ncbi.nlm.nih.gov/gene/204 |
| Ensembl ID | ENSG00000104447 |
| UniProt ID | P54819 |
| OMIM ID | 103020 |
| HGNC ID | 362 |
| Aliases | ADK2, adenylate kinase 2, ATP-AMP transphosphorylase 2 |
Description
The AK2 gene encodes adenylate kinase 2, a mitochondrial enzyme that catalyzes the reversible transfer of phosphate groups between adenine nucleotides (ATP + AMP ↔ 2 ADP). This enzyme is critical for cellular energy homeostasis, particularly in tissues with high energy demands. AK2 is essential for the development and function of the immune system, and mutations in this gene cause reticular dysgenesis, a severe form of severe combined immunodeficiency (SCID).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Reticular dysgenesis (OMIM 267500) | Loss-of-function mutations in AK2 lead to impaired mitochondrial adenylate kinase activity, disrupting energy metabolism in hematopoietic stem cells and causing severe leukopenia, lymphopenia, and sensorineural deafness. | ClinVar, OMIM |
| Severe combined immunodeficiency (SCID) (OMIM 267500) | AK2 deficiency impairs the development of both T and B lymphocytes, leading to profound immunodeficiency. The mechanism involves defective energy supply for lymphocyte differentiation and proliferation. | ClinVar, OMIM |
| Sensorineural hearing loss (associated with reticular dysgenesis) | AK2 is expressed in the inner ear; its deficiency leads to mitochondrial dysfunction in hair cells, causing hearing impairment. | OMIM, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (nTPM ~ 100) | High |
| Heart | High (nTPM ~ 80) | High |
| Skeletal Muscle | Medium (nTPM ~ 50) | Medium |
| Kidney | Medium (nTPM ~ 40) | Medium |
| Brain | Low (nTPM ~ 10) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | High | Hepatocellular carcinoma cell line |
| K562 (leukemia) | Medium | Chronic myelogenous leukemia |
| A549 (lung) | Low | Lung carcinoma |
| MCF7 (breast) | Low | Breast adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.592A>G (p.Thr198Ala) | Missense | Rare (found in reticular dysgenesis) | Reduced enzyme activity, leading to immune deficiency |
| c.433C>T (p.Arg145Ter) | Nonsense | Rare (found in reticular dysgenesis) | Premature truncation, loss of function |
| c.IVS2+1G>A | Splice site | Rare (found in reticular dysgenesis) | Aberrant splicing, loss of function |
| c.1A>G (p.Met1Val) | Start codon loss | Rare (found in reticular dysgenesis) | Loss of translation initiation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most AK2 mutations are loss-of-function, leading to reduced or absent adenylate kinase activity. This impairs mitochondrial energy metabolism, particularly in hematopoietic cells, causing reticular dysgenesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for AK2.
Dominant Negative (DN)
No dominant-negative mutations have been described; AK2 mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • Adenylate kinase activity (GO:0004017) | • ATP binding (GO:0005524) |
| • AMP binding (GO:0016208) | • Mitochondrion (GO:0005739) |
| • Nucleotide metabolism (GO:0009165) |
Pathways
• Purine metabolism (KEGG: hsa00230)
• Adenine nucleotide metabolism (Reactome: R-HSA-8956321)
Protein Summary
The AK2 protein is a 239-amino-acid mitochondrial enzyme that belongs to the adenylate kinase family. It exists as a homodimer and catalyzes the interconversion of adenine nucleotides, playing a key role in cellular energy homeostasis. The protein is localized in the mitochondrial intermembrane space and is essential for maintaining the adenine nucleotide pool. Defects in AK2 lead to reticular dysgenesis, a rare autosomal recessive disorder characterized by severe combined immunodeficiency and sensorineural deafness.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AK2 Knockout HEK293 Cell Line | EDJ-KQ2830 | Human | 204 | Details Get a Quote |
| AK2 Knockout A-549 Cell Line | EDJ-KQ23810 | Human | 204 | Details Get a Quote |
| AK2 Knockout HCT 116 Cell Line | EDJ-KQ23811 | Human | 204 | Details Get a Quote |
| AK2 Knockout HeLa Cell Line | EDJ-KQ23812 | Human | 204 | Details Get a Quote |
| Ak2 Knockout MEF Cell Line | EDJ-KZ534 | Mouse | 11637 | Details Get a Quote |
