POLDIP3

Chr 22

DNA polymerase delta interacting protein 3

Also known as: PDIP3, PDIP46, SKAR

NCBI Gene: 84271 ENSG00000100227 UniProt: Q9BY77 OMIM: 611520

The protein regulates translation by recruiting ribosomal protein S6 kinase beta-1 to mRNAs and enhances translational efficiency of spliced mRNAs. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early infancy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.52), consistent with its role in fundamental cellular processes affecting neurodevelopment.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an RRM (RNA recognition motif)-containing protein that participates in the regulation of translation by recruiting ribosomal protein S6 kinase beta-1 to mRNAs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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

0.52

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.118

Z-score 3.24

OE 0.27 (0.14–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.12Z-score

OE missense 0.98 (0.88–1.09)

247 obs / 252.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.14–0.52)

0≤0.351.4

Missense OE?0.98 (0.88–1.09)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 6 / 22.6Missense obs/exp: 247 / 252.5Syn Z: -0.66

Background carrier burden — how many people carry a rare variant somewhere in POLDIP3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

607 rare PASS variants

Rare truncating (LoF)

1 in 4,800

39 rare PASS variants

Rare synonymous (reference)

1 in 230

250 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for POLDIP3. 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 160	1 in 6,300
South Asian	~43k	1 in 99	1 in 1,800
Remaining (unassigned)	~30k	1 in 77	≈ 1 in 7,500
European (Finnish)	~27k	1 in 330	≈ 1 in 25,000
Admixed American	~22k	1 in 83	≈ 1 in 4,500
African / African American	~21k	1 in 86	1 in 2,900
East Asian	~20k	1 in 130	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 380	none seen
Middle Eastern	~2,884	1 in 170	≈ 1 in 1,300

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.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓