PITPNM3

Chr 17AD

PITPNM family member 3

Also known as: ACKR6, CORD5, NIR1, RDGBA3

NCBI Gene: 83394 ENSG00000091622 UniProt: Q9BZ71 OMIM: 608921

This protein catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes and binds calcium ions. Mutations cause autosomal dominant cone-rod dystrophy 5, affecting retinal function and vision. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.21), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.211 OMIM phenotype

Clinical Summary— PITPNM3

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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.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 517 VUS of 1006 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.09 (0.04–0.21)

0≤0.351.4

Missense OE?0.77 (0.71–0.83)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 4 / 44.5Missense obs/exp: 460 / 598.7Syn Z: -0.78

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedPITPNM3-related cone-rod dystrophyOTHERAD

This gene — mechanism propensity

0.3395th %ile

GOF

0.3094th %ile

LOF

0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

1006 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic1

VUS517

Likely Benign369

Benign87

Conflicting30

Pathogenic

Likely Pathogenic

517

VUS

369

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	1	0	0	0	1
VUS	10	411	88	8	517
Likely Benign	0	10	138	221	369
Benign	0	5	68	14	87
Conflicting	—				30
Total	13	426	294	243	1,006

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap PITPNM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →