POLA2

Chr 11

DNA polymerase alpha 2, accessory subunit

NCBI Gene: 23649ENSG00000014138UniProt: Q14181

Predicted to enable DNA binding activity. Involved in DNA replication initiation and DNA replication, synthesis of primer. Located in ciliary basal body; cytosol; and nucleoplasm. Part of alpha DNA polymerase:primase complex. [provided by Alliance of Genome Resources, Jul 2025]

112
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— POLA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 78 VUS of 112 total submissions

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.
0.65LOEUF
pLI 0.000
Z-score 3.29
OE 0.43 (0.30–0.65)
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.
1.06Z-score
OE missense 0.84 (0.76–0.92)
278 obs / 332.3 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.0.43 (0.30–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.76–0.92)
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.0.98
0≤1.21.6
LoF obs/exp: 17 / 39.2Missense obs/exp: 278 / 332.3Syn Z: 0.19

ClinVar Variant Classifications

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS78
Likely Benign1
Conflicting1
7
Pathogenic
3
Likely Pathogenic
78
VUS
1
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
1
2
0
3
VUS
0
75
3
0
78
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Conflicting
—1
Total07712090

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

View in ClinVar →

Protein Context — Lollipop Plot

POLA2 · 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
Identification of specific susceptibility loci for the early-onset colorectal cancer.
Wang H et al.·Genome Med
2023
Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder.
Kvarnung M et al.·Eur J Hum Genet
2025Case report
The Biological Function of POLA2 in Hepatocellular Carcinoma.
Yang Z et al.·Comb Chem High Throughput Screen
2024
Novel SNP improves differential survivability and mortality in non-small cell lung cancer patients.
Mah TL et al.·BMC Genomics
2014Cohort
Prognostic Analysis of Differentially Expressed DNA Damage Repair Genes in Bladder Cancer.
Yang Y et al.·Pathol Oncol Res
2022
GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels.
Casares-Marfil D et al.·PLoS Negl Trop Dis
2021
Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions.
Lu YC et al.·Clin Cancer Res
2014
Molecular resistance fingerprint of pemetrexed and platinum in a long-term survivor of mesothelioma.
Røe OD et al.·PLoS One
2012Case report
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools