PITPNA

Chr 17

phosphatidylinositol transfer protein alpha

Also known as: HEL-S-36, PI-TPalpha, PITPN, VIB1A

NCBI Gene: 5306ENSG00000174238UniProt: Q00169

This gene encodes a member of a family of lipid-binding proteins that transfer molecules of phosphatidylinositol or phosphatidylcholine between membrane surfaces. The protein is implicated in phospholipase C signaling and in the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) by phosphoinositide-3-kinase.[provided by RefSeq, Sep 2009]

136
ClinVar variants
101
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PITPNA
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
101 Pathogenic / Likely Pathogenic· 34 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.33LOEUF
pLI 0.965
Z-score 3.94
OE 0.13 (0.06–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.44Z-score
OE missense 0.44 (0.36–0.54)
67 obs / 151.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.06–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.36–0.54)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 3 / 23.7Missense obs/exp: 67 / 151.7Syn Z: -0.18

ClinVar Variant Classifications

136 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic17
VUS34
Likely Benign1
84
Pathogenic
17
Likely Pathogenic
34
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
84
0
84
Likely Pathogenic
0
0
17
0
17
VUS
0
18
16
0
34
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total0191170136

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PITPNA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis.
Zhang F et al.·Rev Invest Clin
2024
Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy.
Vieira NM et al.·Proc Natl Acad Sci U S A
2017
Testing of candidate single nucleotide variants associated with paclitaxel neuropathy in the trial NCCTG N08C1 (Alliance).
Boora GK et al.·Cancer Med
2016Meta-analysis
PDE10A Inhibition Reduces the Manifestation of Pathology in DMD Zebrafish and Represses the Genetic Modifier PITPNA.
Lambert MR et al.·Mol Ther
2021Functional
Genome-Wide Association Study Identifies a Locus at 17p13 to Be Associated With Intestinal Malrotation.
Gaitanidis A et al.·World J Surg
2025
Molecular characterization of KMT2A fusion partner genes in 13 cases of pediatric leukemia with complex or cryptic karyotypes.
Ney Garcia DR et al.·Hematol Oncol
2017Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools