PITPNM1

Chr 11

phosphatidylinositol transfer protein membrane associated 1

Also known as: DRES9, NIR2, PITPNM, RDGB, RDGB1, RDGBA, RDGBA1, Rd9

NCBI Gene: 9600 ENSG00000110697 UniProt: O00562 OMIM: 608794

The protein catalyzes phosphatidylinositol transfer between cellular membranes and is essential for maintaining normal endoplasmic reticulum and Golgi apparatus structure, protein export, and cytokinesis completion. Mutations cause autosomal recessive pontocerebellar hypoplasia type 6, a severe neurodevelopmental disorder with prenatal or early infantile onset affecting brain development. The gene is highly constrained against loss-of-function variation, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

PITPNM1 belongs to a family of membrane-associated phosphatidylinositol transfer domain-containing proteins that share homology with the Drosophila retinal degeneration B (rdgB) protein (Ocaka et al., 2005 [PubMed 15627748]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.43

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.43LOEUF

pLI 0.001

Z-score 5.06

OE 0.29 (0.20–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.19Z-score

OE missense 0.69 (0.64–0.74)

565 obs / 822.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.29 (0.20–0.43)

0≤0.351.4

Missense OE?0.69 (0.64–0.74)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 17 / 58.9Missense obs/exp: 565 / 822.5Syn Z: -0.56

Background carrier burden — how many people carry a rare variant somewhere in PITPNM1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 42

1,493 rare PASS variants

Rare truncating (LoF)

1 in 1,500

184 rare PASS variants

Rare synonymous (reference)

1 in 47

791 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PITPNM1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 54	1 in 1,300
South Asian	~43k	1 in 31	1 in 2,400
Remaining (unassigned)	~30k	1 in 41	1 in 780
European (Finnish)	~27k	1 in 98	1 in 1,400
Admixed American	~22k	1 in 40	1 in 1,400
African / African American	~21k	1 in 37	1 in 1,400
East Asian	~20k	1 in 39	1 in 1,600
Ashkenazi Jewish	~13k	1 in 170	1 in 2,000
Middle Eastern	~2,884	1 in 29	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.