POLDIP3

Chr 22

DNA polymerase delta interacting protein 3

Also known as: PDIP3, PDIP46, SKAR

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.52
Clinical SummaryPOLDIP3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.118
Z-score 3.24
OE 0.27 (0.140.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.12Z-score
OE missense 0.98 (0.881.09)
247 obs / 252.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.140.52)
00.351.4
Missense OE0.98 (0.881.09)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 6 / 22.6Missense obs/exp: 247 / 252.5Syn Z: -0.66
DN
0.6938th %ile
GOF
0.4283th %ile
LOF
0.4726th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

POLDIP3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC