POLD2

Chr 7

DNA polymerase delta 2, accessory subunit

NCBI Gene: 5425ENSG00000106628UniProt: P49005

This gene encodes the 50-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein is required for the stimulation of DNA polymerase delta activity by the processivity cofactor proliferating cell nuclear antigen (PCNA). Expression of this gene may be a marker for ovarian carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Mar 2012]

406
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— POLD2
🧬
Gene-Disease Validity (ClinGen)
non-severe combined immunodeficiency due to polymerase delta deficiency · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 220 VUS of 406 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.69LOEUF
pLI 0.001
Z-score 2.66
OE 0.40 (0.24–0.69)
Tolerant

Typical tolerance to LoF variation

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.
1.65Z-score
OE missense 0.73 (0.65–0.82)
212 obs / 291.0 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.0.40 (0.24–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.65–0.82)
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: 9 / 22.7Missense obs/exp: 212 / 291.0Syn Z: 0.58

ClinVar Variant Classifications

406 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS220
Likely Benign144
Benign17
Conflicting2
22
Pathogenic
1
Likely Pathogenic
220
VUS
144
Likely Benign
17
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
8
166
40
6
220
Likely Benign
0
0
64
80
144
Benign
0
0
10
7
17
Conflicting
—2
Total816613793406

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

View in ClinVar →

Protein Context — Lollipop Plot

POLD2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PARP1 and POLD2 as prognostic biomarkers for multiple myeloma in autologous stem cell transplant.
Thomas M et al.·Haematologica
2023
POLD2 and KSP37 (FGFBP2) correlate strongly with histology, stage and outcome in ovarian carcinomas.
Elgaaen BV et al.·PLoS One
2010
ShRNA-based POLD2 expression knockdown sensitizes glioblastoma to DNA-Damaging therapeutics.
Xu Q et al.·Cancer Lett
2020
DNA Polymerase Delta 2 Activates Cell Cycle in Lung Adenocarcinoma, Leading to High Malignancy and Poor Prognosis.
Hashinokuchi A et al.·Ann Surg Oncol
2025
POLD3 deficiency is associated with severe combined immunodeficiency, neurodevelopmental delay, and hearing impairment.
Mehawej C et al.·Clin Immunol
2023
Identification of Frameshift Variants in POLH Gene Causing Xeroderma Pigmentosum in Two Consanguineous Pakistani Families.
Zamani GY et al.·Genes (Basel)
2022
POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies.
Nicolas E et al.·Gene
2016Review
Using machine learning to discover DNA metabolism biomarkers that direct prostate cancer treatment.
Abroudi AS et al.·Sci Rep
2025
Exome sequencing reveals novel rare variants in Iranian familial multiple sclerosis: The importance of POLD2 in the disease pathogenesis.
Salehi Z et al.·Genomics
2021
FOXP3-based immune risk model for recurrence prediction in small-cell lung cancer at stages I-III.
Jiang M et al.·J Immunother Cancer
2021Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Solid TumorAdvanced Solid TumorMetastatic Cancer

KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II

RECRUITING
NCT05525858Seoul National University Bundang HospitalStarted 2022-09-28
AlectinibAtezolizumabErlotinib

External Resources

Links to major genomics databases and tools