PRIMPOL

Chr 4AD

primase and DNA directed polymerase

Also known as: CCDC111, MYP22, Primpol1

NCBI Gene: 201973 ENSG00000164306 UniProt: Q96LW4 OMIM: 615421

The protein is a DNA primase-polymerase that facilitates DNA replication fork progression by bypassing DNA damage lesions and reinitiating DNA synthesis in both nuclear and mitochondrial DNA. Mutations cause autosomal dominant myopia 22. The gene is not highly constrained against loss-of-function variants (LOEUF 1.328).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a DNA primase-polymerase that belongs to a superfamily of archaeao-eukaryotic primases. Members of this family have primase activity, catalyzing the synthesis of short RNA primers that serve as starting points for DNA synthesis, as well as DNA polymerase activity. The encoded protein facilitates DNA damage tolerance by mediating uninterrupted fork progression after UV irradiation and reinitiating DNA synthesis. An allelic variant in this gene is associated with myopia 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

OMIM ResearchGenerating clinical summary…

ADLOEUF 1.331 OMIM phenotype

Clinical Summary— PRIMPOL

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

90 VUS of 106 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.000

Z-score 0.16

OE 0.97 (0.72–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.30Z-score

OE missense 1.05 (0.95–1.16)

297 obs / 282.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.97 (0.72–1.33)

0≤0.351.4

Missense OE?1.05 (0.95–1.16)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 28 / 28.9Missense obs/exp: 297 / 282.8Syn Z: 0.24

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

VUS90

Likely Benign11

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	3	85	2	0	90
Likely Benign	0	7	1	3	11
Benign	0	4	0	1	5
Total	3	96	3	4	106

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

View in ClinVar →

108 pathogenic / likely-pathogenic (of 121) ClinVar copy-number / structural variants overlap PRIMPOL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →