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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PITPNM2
phosphatidylinositol transfer protein membrane associated 2
Chromosome 12 · 12q24.31
NCBI Gene: 57605Ensembl: ENSG00000090975.15HGNC: HGNC:21044UniProt: A5D8U3
20PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmic side of plasma membraneendoplasmic reticulum-plasma membrane contact sitecalcium ion bindinglipid carrier activityasthmaLiver abscessneurodegenerative diseaseosteoarthritis
✦AI Summary

PITPNM2 is a membrane-associated phosphatidylinositol transfer protein that catalyzes the non-vesicular transport of phosphatidylinositol (PI) and phosphatidylcholine between intracellular membranes and the plasma membrane 1. As a multi-domain protein with an N-terminal PITP domain and calcium-binding capability 1, PITPNM2 functions by extracting PI molecules and depositing them at specific membrane compartments, particularly at endoplasmic reticulum-plasma membrane contact sites to support phosphoinositide synthesis 1. PITPNM2 plays a critical role in T cell receptor (TCR) signaling by promoting phosphatidylinositol 4,5-bisphosphate (PIP2) replenishment following TCR stimulation, essential for calcium mobilization and thymocyte development 2. The gene is located on chromosome 12 3 and shares evolutionary conservation with Drosophila rdgB, with rdgB knockdown reducing nocturnal sleep in fruit flies, suggesting conserved sleep-regulatory functions 4. Dysregulated PITPNM2 expression associates with multiple diseases: it is identified as a biomarker in glioblastoma progression where lower expression correlates with disease advancement 5, shows altered expression in breast cancer with associations to poor overall survival 6, and rare variants are implicated in bipolar disorder 7. These findings position PITPNM2 as a key regulator of lipid dynamics with implications for immune signaling and neurological disease.

Sources cited
1
PITPNM2 is a multi-domain membrane-associated PITP that transfers PI between membranes at contact sites to regulate phosphoinositide synthesis
PMID: 23086419
2
PITPNM2 (Nir3) promotes PIP2 replenishment after TCR stimulation, important for T cell development and calcium signaling
PMID: 36581712
3
PITPNM2 is located on chromosome 12p24 and contains PITP and calcium-binding domains homologous to Drosophila rdgB
PMID: 15627748
4
rdgB (PITPNM2 homolog) knockdown reduces nocturnal sleep in Drosophila, suggesting conserved sleep functions
PMID: 36586419
5
PITPNM2 identified as glioblastoma biomarker; lower expression associated with GBM progression
PMID: 37482563
6
PITPNM2 among lipid transport proteins with perturbed expression in breast cancer associated with low overall survival
PMID: 39505903
7
Rare PITPNM2 missense variant identified in bipolar disorder discovery cohort, located in schizophrenia GWAS locus
PMID: 28195573
Disease Associationsⓘ20
asthmaOpen Targets
0.33Weak
Liver abscessOpen Targets
0.32Weak
neurodegenerative diseaseOpen Targets
0.30Weak
osteoarthritisOpen Targets
0.30Weak
joint diseaseOpen Targets
0.27Weak
type 2 diabetes mellitusOpen Targets
0.26Weak
intelligenceOpen Targets
0.24Weak
cartilage diseaseOpen Targets
0.23Weak
schizophreniaOpen Targets
0.18Weak
diabetes mellitusOpen Targets
0.17Weak
Tourette syndromeOpen Targets
0.17Weak
allergic asthmaOpen Targets
0.13Weak
attention deficit hyperactivity disorderOpen Targets
0.10Weak
osteoarthritis, kneeOpen Targets
0.10Suggestive
insomniaOpen Targets
0.10Suggestive
major depressive disorderOpen Targets
0.09Suggestive
obsessive-compulsive disorderOpen Targets
0.09Suggestive
TinnitusOpen Targets
0.09Suggestive
autism spectrum disorderOpen Targets
0.09Suggestive
multiple sclerosisOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PTK2BProtein interaction88%VAPAProtein interaction81%VAPBProtein interaction76%PITPNM1Shared pathway44%PITPNC1Shared pathway40%PITPNM3Shared pathway40%
Tissue Expression6 tissues
Liver
100%
Ovary
84%
Lung
49%
Bone Marrow
27%
Heart
26%
Brain
17%
Gene Interaction Network
Click a node to explore
PITPNM2PTK2BVAPAVAPBPITPNM1PITPNC1PITPNM3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9BZ72
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.36Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.27 [0.21–0.36]
RankingsWhere PITPNM2 stands among ~20K protein-coding genes
  • #14,224of 20,598
    Most Researched20
  • #1,618of 17,882
    Most Constrained (LOEUF)0.36 · top 10%
Genes detectedPITPNM2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Adipocytes reprogram the proteome of breast cancer cells in organotypic three-dimensional cell cultures.
PMID: 39505903
Sci Rep · 2024
1.00
2
The diverse functions of phosphatidylinositol transfer proteins.
PMID: 23086419
Curr Top Microbiol Immunol · 2012
0.90
3
Gene co-expression network construction and analysis for identification of genetic biomarkers associated with glioblastoma multiforme using topological findings.
PMID: 37482563
J Egypt Natl Canc Inst · 2023
0.80
4
rdgB knockdown in neurons reduced nocturnal sleep in Drosophila melanogaster.
PMID: 36586155
Biochem Biophys Res Commun · 2023
0.70
5
ELF4 is a critical component of a miRNA-transcription factor network and is a bridge regulator of glioblastoma receptor signaling and lipid dynamics.
PMID: 35862252
Neuro Oncol · 2023
0.60