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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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NKAIN2
sodium/potassium transporting ATPase interacting 2
Chromosome 6 Β· 6q22.31
NCBI Gene: 154215Ensembl: ENSG00000188580.16HGNC: HGNC:16443UniProt: B0AZU5
22PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of sodium ion transportplasma membranesmoking initiationtreatment-resistant hypertensionmajor depressive disorderattention deficit hyperactivity disorder
✦AI Summary

NKAIN2 (sodium/potassium transporting ATPase interacting 2) is a gene located on chromosome 6 that regulates sodium ion transport through interaction with Na+/K+-ATPase enzymes 1. The gene exhibits multiple functional roles across different biological contexts. In neuropsychiatric disorders, NKAIN2 shows sex-dependent genetic effects on schizophrenia, bipolar disorder, and major depressive disorder risk, implicating neuronal excitability mechanisms 1. A genome-wide association study identified NKAIN2 as a modifier gene associated with negative symptoms in schizophrenia 2, and NKAIN2 emerged as a top contributor to ADHD pharmacological treatment response prediction 3. NKAIN2 functions as a putative tumor suppressor gene located within the commonly deleted 6q region. In prostate cancer, NKAIN2 overexpression inhibits cellular growth, promotes apoptosis, and suppresses migration and invasion, while knockdown produces opposing effects 4. In pancreatic cancer, NKAIN2 is directly targeted by miR-181d, and its downregulation suppresses cancer development 5. Neuroblastoma studies revealed high NKAIN2 expression in aggressive tumors and MYCN-amplified cell lines, with downregulation during differentiation 6. Additionally, NKAIN2 shows positive selection signals in Tibetan pigs, suggesting roles in cardiorespiratory adaptation to high-altitude hypoxia 7.

Sources cited
1
NKAIN2 locus shows genome-wide significant SNP-by-sex interaction across schizophrenia, bipolar disorder, and major depressive disorder, implicating neuronal excitability
PMID: 34099189
2
NKAIN2 identified as modifier gene associated with negative symptoms in schizophrenia through gene-based association analysis
PMID: 26316594
3
NKAIN2 variant contributed most to CNN model predicting ADHD pharmacological treatment response and is associated with metabolic processes
PMID: 39920114
4
NKAIN2 overexpression inhibits prostate cancer growth, promotes apoptosis, and suppresses migration/invasion; functions as novel tumor suppressor
PMID: 27588475
5
NKAIN2 is directly targeted by miR-181d; NKAIN2 downregulation suppresses pancreatic cancer development, proliferation, and migration
PMID: 28381166
6
NKAIN2 expressed at high levels in neuroblastoma cell lines and aggressive lesions; downregulated during differentiation
PMID: 24205241
7
NKAIN2 identified with strong positive selection signals in Tibetan pigs, likely improving cardiorespiratory function for high-altitude adaptation
PMID: 39457085
Disease Associationsβ“˜20
smoking initiationOpen Targets
0.36Weak
treatment-resistant hypertensionOpen Targets
0.34Weak
major depressive disorderOpen Targets
0.31Weak
attention deficit hyperactivity disorderOpen Targets
0.29Weak
insomniaOpen Targets
0.28Weak
anaphylaxisOpen Targets
0.28Weak
hypotensionOpen Targets
0.28Weak
malunion fractureOpen Targets
0.28Weak
ventricular fibrillationOpen Targets
0.28Weak
substance abuseOpen Targets
0.27Weak
type 2 diabetes mellitusOpen Targets
0.26Weak
ptosisOpen Targets
0.26Weak
Abnormality of the skeletal systemOpen Targets
0.26Weak
placental retentionOpen Targets
0.25Weak
Abruptio PlacentaeOpen Targets
0.25Weak
abscessOpen Targets
0.25Weak
cellulitisOpen Targets
0.25Weak
injuryOpen Targets
0.25Weak
male infertilityOpen Targets
0.25Weak
pernicious anemiaOpen Targets
0.25Weak
Pathogenic Variants1
GRCh38/hg38 6q22.31(chr6:124116341-124499647)x1Pathogenic
See cases
β˜…β˜†β˜†β˜†2011
View on ClinVar β†—
Related Genes
NKAIN1Shared pathway100%NKAIN4Shared pathway100%NKAIN3Shared pathway100%SENP6Protein interaction91%ATP1B1Protein interaction78%SLC25A4Protein interaction73%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
8%
Heart
3%
Ovary
1%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
NKAIN2NKAIN1NKAIN4NKAIN3SENP6ATP1B1SLC25A4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q5VXU1
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.90LoF Tolerant
pLIβ“˜
0.26Tolerant
Observed/Expected LoF0.43 [0.22–0.90]
RankingsWhere NKAIN2 stands among ~20K protein-coding genes
  • #13,705of 20,598
    Most Researched22
  • #5,349of 5,498
    Most Pathogenic Variants1
  • #8,195of 17,882
    Most Constrained (LOEUF)0.90
Genes detectedNKAIN2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.
PMID: 34099189
Biol Psychiatry Β· 2022
1.00
2
The structure and function of NKAIN2-a candidate tumor suppressor.
PMID: 26770299
Int J Clin Exp Med Β· 2015
0.90
3
Downregulation of microRNA-181d had suppressive effect on pancreatic cancer development through inverse regulation of KNAIN2.
PMID: 28381166
Tumour Biol Β· 2017
0.80
4
Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes.
PMID: 26316594
Schizophr Bull Β· 2016
0.70
5
Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder.
PMID: 39920114
Transl Psychiatry Β· 2025
0.60