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3 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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NIPAL3
NIPA like domain containing 3
Chromosome 1 Β· 1p36.11
NCBI Gene: 57185Ensembl: ENSG00000001461.19HGNC: HGNC:25233UniProt: A6NN97
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingmagnesium ion transportmembranemagnesium ion transmembrane transporter activitynervous system diseaseAbnormality of the integumentdyspepsiacutaneous melanoma
✦AI Summary

NIPAL3 (NIPA-like domain containing 3) is a ubiquitously expressed, highly conserved protein 1 involved in magnesium ion transport and protein binding functions. The gene encodes a membrane-associated protein with structural similarity to NIPA family members, which are known receptors and transporters 1. At the molecular level, NIPAL3 functions within competing endogenous RNA networks in keloid fibroblasts, where it serves as a target gene regulated by the long noncoding RNA HOXA11-AS through three microRNAs (hsa-miR-19a-3p, hsa-miR-141-3p, and hsa-miR-140-5p) 2. In skeletal muscle, NIPAL3 was identified as a key interacting gene associated with long-term exercise responses in older adults through artificial neural network analysis 3, though RT-qPCR validation did not show significant differential expression following 6 months of resistance training 3. Clinically, NIPAL3 deficiency results in pleiotropic phenotypes in knockout mouse models, including behavioral impairments, decreased natural killer cell numbers, and immune dysregulation 1. Notably, mutant males exhibited increased IgE levels and impaired lung function, suggesting a role in atopic disease pathogenesis 1. Given that the human NPAL3 gene maps to 1p36.12-p35.1, a region previously linked to atopic diseases, NPAL3 may represent a candidate gene for allergic and immunological disorders.

Sources cited
1
NPAL3 is ubiquitously expressed and conserved; Npal3 knockout mice show behavioral deficits, altered immune function (decreased NK cells, changed immunoglobulin levels), increased IgE in males, and impaired lung function; NPAL3 is located in a genomic region linked to atopic diseases
PMID: 19738379
2
NIPAL3 is a target gene in a competing endogenous RNA network involving HOXA11-AS and three microRNAs (hsa-miR-19a-3p, hsa-miR-141-3p, hsa-miR-140-5p) in keloid fibroblasts
PMID: 35432479
3
NIPAL3 was identified as a main interacting gene associated with long-term exercise in older adults, though RT-qPCR showed no significant differential expression after 6 months of resistance training
PMID: 39210538
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜20
nervous system diseaseOpen Targets
0.28Weak
Abnormality of the integumentOpen Targets
0.28Weak
dyspepsiaOpen Targets
0.27Weak
cutaneous melanomaOpen Targets
0.27Weak
hair colorOpen Targets
0.26Weak
Neurodevelopmental disorderOpen Targets
0.12Weak
prostate carcinomaOpen Targets
0.07Suggestive
isolated agammaglobulinemiaOpen Targets
0.05Suggestive
immunodeficiency 18Open Targets
0.05Suggestive
classic Hodgkin lymphomaOpen Targets
0.05Suggestive
Hodgkins lymphomaOpen Targets
0.05Suggestive
macroglobulinemia, Waldenstrom, 1Open Targets
0.04Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.04Suggestive
hyper-IgM syndrome type 3Open Targets
0.04Suggestive
immunodeficiency 105Open Targets
0.04Suggestive
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets
0.04Suggestive
T-B+ severe combined immunodeficiency due to JAK3 deficiencyOpen Targets
0.04Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.04Suggestive
agammaglobulinemia 7, autosomal recessiveOpen Targets
0.04Suggestive
immunodeficiency 86Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar β†—
Related Genes
NIPAL4Shared pathway100%NIPAL1Shared pathway100%NIPA1Shared pathway100%NIPA2Shared pathway100%NIPAL2Shared pathway100%MAGT1Protein interaction68%
Tissue Expression6 tissues
Brain
100%
Heart
44%
Bone Marrow
26%
Lung
14%
Ovary
11%
Liver
7%
Gene Interaction Network
Click a node to explore
NIPAL3NIPAL4NIPAL1NIPA1NIPA2NIPAL2MAGT1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6P499
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.09LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.82 [0.62–1.09]
RankingsWhere NIPAL3 stands among ~20K protein-coding genes
  • #13,964of 20,598
    Most Researched21
  • #11,134of 17,882
    Most Constrained (LOEUF)1.09
Genes detectedNIPAL3
Sources retrieved3 papers
Response timeβ€”
πŸ“„ Sources
3
1
Artificial neural network inference analysis identified novel genes and gene interactions associated with skeletal muscle aging.
PMID: 39210538
J Cachexia Sarcopenia Muscle Β· 2024
1.00
2
Construction of a HOXA11-AS-Interact Ed Network in Keloid Fibroblasts Using Integrated Bioinformatic Analysis and
PMID: 35432479
Front Genet Β· 2022
0.67
3
Targeted disruption of the mouse Npal3 gene leads to deficits in behavior, increased IgE levels, and impaired lung function.
PMID: 19738379
Cytogenet Genome Res Β· 2009
0.33