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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ANKK1
ankyrin repeat and kinase domain containing 1
Chromosome 11 · 11q23.2
NCBI Gene: 255239Ensembl: ENSG00000170209.5HGNC: HGNC:21027UniProt: Q8NFD2
158PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of cell cycle processprotein bindingnucleuscytoplasmmetabolic syndromeneurotic disordernervous system diseaseschizophrenia
✦AI Summary

ANKK1 (ankyrin repeat and kinase domain containing 1) is a serine/threonine RIP-family kinase located on chromosome 11 that functions as a scaffold protein in dopaminergic neurotransmission and neural development 1. The gene contains a kinase domain and 11 ankyrin repeats and is expressed exclusively in astrocytes within the central nervous system, with expression upregulated by dopaminergic agonists 2. ANKK1 serves as a Wnt/PCP scaffold protein that interacts with FARP1 and WGEF to regulate RhoGTPase activation and F-actin assembly during neuritogenesis and neuronal migration 3. It likely regulates DRD2 expression through NF-kappaB signaling 1. The TaqIA polymorphism (rs1800497) located in ANKK1 exon 8 has been extensively studied in psychiatric and neurological disorders. This variant shows association with attention deficit hyperactivity disorder (ADHD) in a dominant model (OR=1.785, p=0.027), particularly in African populations 4, and with migraine susceptibility 5. The polymorphism also influences impulsivity through gene-by-environment interactions with paternal maltreatment 6 and contributes to adolescent smoking risk through effects on striatal dopamine signaling 7. However, meta-analysis found no significant associations between ANKK1 polymorphisms and executive function domains in healthy adults 8.

Sources cited
1
ANKK1 gene structure (kinase domain and 11 ankyrin repeats), RIP kinase family membership, NF-kappaB regulation of DRD2, and activation by dopaminergic agonists
PMID: 22232965
2
ANKK1 expression exclusively in astrocytes within CNS and upregulation by apomorphine (dopaminergic agonist)
PMID: 19853839
3
ANKK1 functions as Wnt/PCP scaffold protein, interacts with FARP1 and WGEF, regulates RhoGTPase activation and F-actin assembly in neuritogenesis and neuronal migration
PMID: 39409035
4
ANKK1 rs1800497 (TaqIA) polymorphism association with ADHD (pooled OR=1.785, p=0.027) in dominant model
PMID: 25641135
5
ANKK1 rs1800497 polymorphism association with migraine susceptibility and gene interactions with DBH variants
PMID: 22875483
6
ANKK1-rs1800497-T allele interacts with paternal maltreatment and TH variant to increase cognitive/attentive impulsivity
PMID: 35935430
7
TTC12-ANKK1-DRD2 cluster involvement in adolescent smoking through effects on striatal dopamine signaling and reward response
PMID: 30104163
8
Meta-analysis found no significant association between ANKK1 Taq1A polymorphism and executive function domains in healthy adults
PMID: 30836122
Disease Associationsⓘ20
metabolic syndromeOpen Targets
0.35Weak
neurotic disorderOpen Targets
0.25Weak
nervous system diseaseOpen Targets
0.13Weak
schizophreniaOpen Targets
0.08Suggestive
Parkinson diseaseOpen Targets
0.08Suggestive
smoking cessationOpen Targets
0.06Suggestive
attempted suicideOpen Targets
0.05Suggestive
major depressive episodeOpen Targets
0.05Suggestive
suicide behaviourOpen Targets
0.05Suggestive
obesityOpen Targets
0.05Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
cannabis dependenceOpen Targets
0.05Suggestive
osteoarthritisOpen Targets
0.05Suggestive
obsessive-compulsive disorderOpen Targets
0.04Suggestive
substance-related disorderOpen Targets
0.04Suggestive
suicidal ideationOpen Targets
0.04Suggestive
depressive disorderOpen Targets
0.04Suggestive
mental or behavioural disorderOpen Targets
0.04Suggestive
mood disorderOpen Targets
0.04Suggestive
X-linked cone dysfunction syndrome with myopiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TTC12Protein interaction95%COMTProtein interaction78%DRD2Protein interaction78%DRD4Protein interaction78%SLC6A3Protein interaction78%SLC6A4Protein interaction78%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
90%
Lung
49%
Liver
34%
Brain
13%
Heart
0%
Gene Interaction Network
Click a node to explore
ANKK1TTC12COMTDRD2DRD4SLC6A3SLC6A4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8NFD2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.38LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.05 [0.81–1.38]
RankingsWhere ANKK1 stands among ~20K protein-coding genes
  • #2,842of 20,598
    Most Researched158 · top quartile
  • #14,383of 17,882
    Most Constrained (LOEUF)1.38
Genes detectedANKK1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Association between ANKK1 (rs1800497) polymorphism of DRD2 gene and attention deficit hyperactivity disorder: a meta-analysis.
PMID: 25641135
Neurosci Lett · 2015
1.00
2
Identification of a novel ANKK1 and other dopaminergic (DRD2 and DBH) gene variants in migraine susceptibility.
PMID: 22875483
Neuromolecular Med · 2013
0.90
3
Associations of the ANKK1 and DRD2 gene polymorphisms with overweight, obesity and hedonic hunger among women from the Northwest of Iran.
PMID: 32020513
Eat Weight Disord · 2021
0.84
4
ANKK1 Is a Wnt/PCP Scaffold Protein for Neural F-ACTIN Assembly.
PMID: 39409035
Int J Mol Sci · 2024
0.80
5
Genetic Aspects of Problematic and Risky Internet Use in Young Men-Analysis of ANKK1, DRD2 and NTRK3 Gene Polymorphism.
PMID: 38397159
Genes (Basel) · 2024
0.80