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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
AK9
adenylate kinase 9
Chromosome 6 Β· 6q21
NCBI Gene: 221264Ensembl: ENSG00000155085.16HGNC: HGNC:33814UniProt: Q5TCS8
29PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinase
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nuclear membranenucleoplasmcytosolnucleoside monophosphate kinase activityspermatogenic failure 89postsynaptic congenital myasthenic syndromePostsynaptic congenital myasthenic syndromesclonal hematopoiesis
✦AI Summary

AK9 is a broad-specificity nucleoside phosphate kinase that catalyzes nucleoside monophosphate phosphorylation, preferentially converting AMP to ADP using ATP as phosphate donor 1. AK9 also exhibits diphosphate kinase activity, producing various NTPs from their diphosphate precursors with substrate preference CDP > UDP > ADP > TDP 1. Localized to the nucleus, cytoplasm, and nucleoplasm, AK9 maintains cellular nucleotide homeostasis and energy metabolism 2. In sperm, AK9 functions as a critical component of the adenylate kinase phosphate energy shuttle, localizing to the flagellar axoneme radial spoke where it cooperatively regulates ATP transfer with AK8 3. Bi-allelic AK9 mutations cause asthenozoospermia (reduced sperm motility) through destabilization of sperm nucleotide homeostasis and inhibition of glycolysis, though intracytoplasmic sperm injection effectively rescues fertility 2. AK9 mutations are implicated in neuromuscular and neurological disorders: digenic AK9/RAPSN mutations cause congenital myasthenic syndrome through impaired N-glycosylation dependent on nucleotide availability 4, and heterozygous AK9 mutations contribute to idiopathic normal pressure hydrocephalus by impairing ependymal ciliary motility 5. Additionally, AK9 functions as a tumor suppressor in lung cancer, with rs1321328 reducing AK9 expression through altered m6A methylation 6.

Sources cited
1
AK9 deficiency causes asthenozoospermia through destabilized nucleotide homeostasis and impaired glycolysis in sperm; ICSI rescues fertility in affected patients
PMID: 37713809
2
AK9 localizes to flagellar axoneme radial spoke and cooperatively regulates ATP transfer with AK8 to promote sperm motility
PMID: 38761355
3
AK9 mutations cause congenital myasthenic syndrome as disease modifier by providing nucleotides for N-glycosylation
PMID: 27966543
4
Heterozygous AK9 mutations impair ependymal ciliary motility and cause communicating hydrocephalus in idiopathic normal pressure hydrocephalus
PMID: 38100419
5
AK9 acts as tumor suppressor in lung cancer; rs1321328 reduces AK9 expression through m6A modification
PMID: 38051288
6
AK9 catalyzes adenine nucleotide interconversion preferentially with AMP and ATP substrates; possesses both monophosphate and diphosphate kinase activities
PMID: 24495878
Disease Associationsβ“˜21
spermatogenic failure 89Open Targets
0.47Moderate
postsynaptic congenital myasthenic syndromeOpen Targets
0.37Weak
Postsynaptic congenital myasthenic syndromesOpen Targets
0.37Weak
clonal hematopoiesisOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.29Weak
pulmonary edemaOpen Targets
0.27Weak
placenta praeviaOpen Targets
0.24Weak
cardiac transplantOpen Targets
0.22Weak
poisoningOpen Targets
0.15Weak
atrial fibrillationOpen Targets
0.12Weak
COVID-19Open Targets
0.11Weak
Abruptio PlacentaeOpen Targets
0.10Suggestive
azoospermiaOpen Targets
0.10Suggestive
spermatogenic failure 3Open Targets
0.08Suggestive
spermatogenic failure 55Open Targets
0.08Suggestive
spermatogenic failure 83Open Targets
0.08Suggestive
spermatogenic failure 7Open Targets
0.08Suggestive
gestational diabetesOpen Targets
0.08Suggestive
spermatogenic failure 16Open Targets
0.07Suggestive
spermatogenic failure 21Open Targets
0.07Suggestive
Spermatogenic failure 89UniProt
Pathogenic Variants3
NM_001145128.3(AK9):c.4872_4875dup (p.Cys1626fs)Pathogenic
Spermatogenic failure 89
β˜†β˜†β˜†β˜†2024β†’ Residue 1626
NM_001145128.3(AK9):c.2005dup (p.Cys669fs)Pathogenic
Spermatogenic failure 89
β˜†β˜†β˜†β˜†2024β†’ Residue 669
NM_001145128.3(AK9):c.2444C>T (p.Pro815Leu)Pathogenic
Spermatogenic failure 89
β˜†β˜†β˜†β˜†2024β†’ Residue 815
View on ClinVar β†—
Related Genes
ATP5F1AProtein interaction100%ATP5F1CProtein interaction100%NME1-NME2Protein interaction96%NRSN1Protein interaction95%AK1Protein interaction95%ENTPD2Protein interaction95%
Tissue Expression6 tissues
Brain
100%
Heart
56%
Bone Marrow
37%
Ovary
30%
Lung
27%
Liver
22%
Gene Interaction Network
Click a node to explore
AK9ATP5F1AATP5F1CNME1-NME2NRSN1AK1ENTPD2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q5TCS8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.85LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.65–0.85]
RankingsWhere AK9 stands among ~20K protein-coding genes
  • #12,088of 20,598
    Most Researched29
  • #4,120of 5,498
    Most Pathogenic Variants3
  • #7,350of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedAK9
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Deficiency in AK9 causes asthenozoospermia and male infertility by destabilising sperm nucleotide homeostasis.
PMID: 37713809
EBioMedicine Β· 2023
1.00
2
Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes.
PMID: 38761355
Sci China Life Sci Β· 2024
0.90
3
Limb girdle myasthenia with digenic RAPSN and a novel disease gene AK9 mutations.
PMID: 27966543
Eur J Hum Genet Β· 2017
0.80
4
A role for mutations in
PMID: 38100419
Proc Natl Acad Sci U S A Β· 2023
0.70
5
Genetic Risk Factors in Normal Pressure Hydrocephalus: What We Know and What Is Next.
PMID: 40266017
Mov Disord Β· 2025
0.60