PITPNM3

Chr 17AD

PITPNM family member 3

Also known as: ACKR6, CORD5, NIR1, RDGBA3

NCBI Gene: 83394ENSG00000091622UniProt: Q9BZ71

This gene encodes a member of a family of membrane-associated phosphatidylinositol transfer domain-containing proteins. The calcium-binding protein has phosphatidylinositol (PI) transfer activity and interacts with the protein tyrosine kinase PTK2B (also known as PYK2). The protein is homologous to a Drosophila protein that is implicated in the visual transduction pathway in flies. Mutations in this gene result in autosomal dominant cone dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Cone-rod dystrophy 5MIM #600977
AD
533
ClinVar variants
17
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PITPNM3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 325 VUS of 533 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.
0.21LOEUF
pLI 1.000
Z-score 5.63
OE 0.09 (0.04–0.21)
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.
2.01Z-score
OE missense 0.77 (0.71–0.83)
460 obs / 598.7 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.0.09 (0.04–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.71–0.83)
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.1.06
0≤1.21.6
LoF obs/exp: 4 / 44.5Missense obs/exp: 460 / 598.7Syn Z: -0.78

ClinVar Variant Classifications

533 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS325
Likely Benign118
Benign52
Conflicting21
16
Pathogenic
1
Likely Pathogenic
325
VUS
118
Likely Benign
52
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
7
264
52
2
325
Likely Benign
0
6
46
66
118
Benign
0
4
43
5
52
Conflicting
—21
Total727415873533

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

View in ClinVar →

Protein Context — Lollipop Plot

PITPNM3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PITPNM3-related cone-rod dystrophy

limited
ADUndeterminedUncertain
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cone-rod dystrophy 5

MIM #600977

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CCL18 signaling from tumor-associated macrophages activates fibroblasts to adopt a chemoresistance-inducing phenotype.
Zeng W et al.·Oncogene
2023
Generating a Preclinical Model for PITPNM3 and Evaluating Genotype-Phenotype Concordance: Insights from a Mouse Model.
Demirkol A et al.·Cells
2025Functional
Inhibition of breast cancer metastasis via PITPNM3 by pachymic acid.
Hong R et al.·Asian Pac J Cancer Prev
2012
Ocular phenotype of CORD5, an autosomal dominant retinal dystrophy associated with PITPNM3 p.Q626H mutation.
Reinis A et al.·Acta Ophthalmol
2013
AUTOIMMUNE RETINOPATHY IN A PATIENT WITH A MISSENSE MUTATION IN PITPNM3.
Bakhoum MF et al.·Retin Cases Brief Rep
2018Case report
Perturbations of BMP/TGF-β and VEGF/VEGFR signalling pathways in non-syndromic sporadic brain arteriovenous malformations (BAVM).
Wang K et al.·J Med Genet
2018
Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma.
Ye H et al.·Cell Death Dis
2018
Whole-genome sequencing reveals the impact of lipid pathway and APOE genotype on brain amyloidosis.
Patel M et al.·Hum Mol Genet
2025
A novel GUCY2D mutation in a Chinese family with dominant cone dystrophy.
Zhao X et al.·Mol Vis
2013Case report
Identification of Novel Molecular Subtypes of Prostate Cancer Based on Genes Related to Metabolic Reprogramming to Assess Prognosis and Immune Landscape.
Fan W et al.·Crit Rev Eukaryot Gene Expr
2025Review
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