POLDIP2

Chr 17

DNA polymerase delta interacting protein 2

Also known as: PDIP38, p38

NCBI Gene: 26073UniProt: Q9Y2S7

This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit, as well as with proliferating cell nuclear antigen. The encoded protein maybe play a role in the ability of the replication fork to bypass DNA lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

0
Active trials
20
ClinVar variants
6
Pathogenic / LP
1.9
Missense Z
0.46
LOEUF
6
Pubs (2 yr)
Clinical Summary— POLDIP2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 2 VUS of 20 total submissions
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.46LOEUF
pLI 0.414
Z-score 3.44
OE 0.22 (0.11–0.46)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.94Z-score
OE missense 0.62 (0.54–0.72)
129 obs / 207.9 exp
Tolerant

Mild missense constraint

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.0.22 (0.11–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.54–0.72)
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.0.93
0≤1.21.6
LoF obs/exp: 5 / 22.7Missense obs/exp: 129 / 207.9Syn Z: 0.51

ClinVar Variant Classifications

20 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS2
Likely Benign1
Benign11
5
Pathogenic
1
Likely Pathogenic
2
VUS
1
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
0
2
0
2
Likely Benign
0
1
0
0
1
Benign
1
0
5
5
11
Total1113520

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

View in ClinVar →

Protein Context — Lollipop Plot

POLDIP2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Endothelial Poldip2 regulates sepsis-induced lung injury via Rho pathway activation.
Dolmatova EV et al.·Cardiovasc Res
2022
Genomic landscape and molecular evolutionary trajectories of renal epithelioid angiomyolipoma and benign angiomyolipoma.
Anwaier A et al.·Neoplasia
2025
The mitochondrial protease ClpP is a druggable target that controls VSMC phenotype by a SIRT1-dependent mechanism.
Paredes F et al.·Redox Biol
2024Functional
Polymerase δ-interacting protein 2 promotes postischemic neovascularization of the mouse hindlimb.
Amanso AM et al.·Arterioscler Thromb Vasc Biol
2014Functional
Essential role of POLDIP2 in Tau aggregation and neurotoxicity via autophagy/proteasome inhibition.
Kim Y et al.·Biochem Biophys Res Commun
2015
mRNA markers associated with malignant pleural effusion.
Hsu SC et al.·Sci Rep
2023
A Mitochondria-Related Signature in Diffuse Large B-Cell Lymphoma: Prognosis, Immune and Therapeutic Features.
Zhou ZZ et al.·Cancer Med
2025
MIR31HG regulates the proliferation, migration and invasion of breast cancer by regulating the expression of POLDIP2.
Xin C et al.·J BUON
2021
The Bacterial ClpXP-ClpB Family Is Enriched with RNA-Binding Protein Complexes.
Auburger G et al.·Cells
2022Review
Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
Paredes F et al.·Circ Res
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction
Eidson LN et al.·Sci Rep
2021
Poldip2 knockdown protects against lipopolysaccharide-induced acute lung injury via Nox4/Nrf2/NF-kappaB signaling pathway
Wang Y et al.·Front Pharmacol
2022
[PolDIP2 regulates mitochondrial functioning and cellular metabolism].
Andjongo É et al.·Med Sci (Paris)
2021
Characterization of Poldip2 knockout mice: Avoiding incorrect gene targeting
Lassègue B et al.·PLoS One
2021
Capsaicin ameliorates diabetic retinopathy by inhibiting poldip2-induced oxidative stress
Liu K et al.·Redox Biol
2022
A unique arginine cluster in PolDIP2 enhances nucleotide binding and DNA synthesis by PrimPol
Kasho K et al.·Nucleic Acids Res
2021
ZEB1 regulates bone metabolism in osteoporotic rats through inducing POLDIP2 transcription
Zhu X et al.·J Orthop Surg Res
2022
MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2
Woo SJ et al.·Int J Mol Sci
2022
Top 8 full-text resultsSearch PubTator3 ↗

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients