PRIMPOL

primase and DNA directed polymerase, the group of DNA polymerases

Basic information

Region (hg38): 4:184649667-184694963

Previous symbols: [ "CCDC111" ]

Links

ENSG00000164306 ∙ NCBI:201973 ∙ OMIM:615421 ∙ HGNC:26575 ∙ Uniprot:Q96LW4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopia 22, autosomal dominant	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	23579484

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRIMPOL gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRIMPOL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			48	3	1	52
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	0	0	50	4	1

Variants in PRIMPOL

This is a list of pathogenic ClinVar variants found in the PRIMPOL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-184657144-A-G		PRIMPOL-related disorder	Uncertain significance (May 12, 2023)
4-184657173-A-T		PRIMPOL-related disorder	Benign (Feb 12, 2024)
4-184657200-G-T		not specified	Uncertain significance (Jan 09, 2024)
4-184657219-G-A		not specified	Uncertain significance (Nov 07, 2024)
4-184657253-C-T		not specified	Uncertain significance (Aug 26, 2024)
4-184657256-C-T		not specified	Uncertain significance (May 29, 2024)
4-184657288-C-G		not specified	Uncertain significance (Apr 10, 2023)
4-184659349-G-A		PRIMPOL-related disorder	Uncertain significance (Aug 07, 2024)
4-184659367-A-G		not specified	Uncertain significance (Mar 19, 2024)
4-184659378-T-C		PRIMPOL-related disorder	Likely benign (Apr 09, 2018)
4-184659380-G-A		not specified	Uncertain significance (Aug 11, 2024)
4-184659386-G-A		not specified	Uncertain significance (Oct 20, 2023)
4-184659403-A-G			Benign (Aug 04, 2018)
4-184659422-T-G		not specified	Uncertain significance (Oct 16, 2024)
4-184659424-T-G		Myopia 22, autosomal dominant • not specified	Uncertain significance (May 04, 2022)
4-184659428-A-G		not specified	Uncertain significance (Dec 22, 2023)
4-184659440-A-G		PRIMPOL-related disorder	Likely benign (Aug 08, 2019)
4-184661787-C-T		not specified	Uncertain significance (Aug 18, 2021)
4-184661800-T-C		PRIMPOL-related disorder	Benign (May 06, 2024)
4-184661848-A-G		not specified	Uncertain significance (Oct 10, 2023)
4-184661860-A-T		not specified	Uncertain significance (Oct 22, 2024)
4-184661873-T-G		not specified	Uncertain significance (Mar 25, 2024)
4-184666010-C-T		not specified	Uncertain significance (Sep 26, 2022)
4-184666032-A-G		not specified	Likely benign (Jul 21, 2021)
4-184672198-G-T		not specified	Uncertain significance (Jul 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRIMPOL	protein_coding	protein_coding	ENST00000314970	12	45351

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.33e-18	0.00542	125130	2	614	125746	0.00245

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.299	297	283	1.05	0.0000137	3705
Missense in Polyphen		97	93.992	1.032		1252
Synonymous	0.244	96	99.1	0.969	0.00000478	990
Loss of Function	0.157	28	28.9	0.969	0.00000148	377

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00192	0.00191
Ashkenazi Jewish	0.00	0.00
East Asian	0.0134	0.0134
Finnish	0.00134	0.00134
European (Non-Finnish)	0.000773	0.000765
Middle Eastern	0.0134	0.0134
South Asian	0.00666	0.00662
Other	0.00115	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA primase and DNA polymerase able to initiate de novo DNA synthesis using dNTPs. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Involved in translesion synthesis via its primase activity by mediating uninterrupted fork progression after programmed or damage-induced fork arrest and by reinitiating DNA synthesis after dNTP depletion. Required for mitochondrial DNA (mtDNA) synthesis, suggesting it may be involved in DNA tolerance during the replication of mitochondrial DNA. Has non-overlapping function with POLH. {ECO:0000269|PubMed:24126761, ECO:0000269|PubMed:24207056, ECO:0000269|PubMed:24240614, ECO:0000269|PubMed:24267451}.
• Disease: DISEASE: Myopia 22, autosomal dominant (MYP22) [MIM:615420]: A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. {ECO:0000269|PubMed:23579484}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.24

Haploinsufficiency Scores

• pHI: 0.149
• hipred: N
• hipred_score: 0.219
• ghis: 0.512

Essentials

• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Primpol
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; reproductive system phenotype; pigmentation phenotype; vision/eye phenotype; immune system phenotype; cellular phenotype

Gene ontology

• Biological process: mitochondrial DNA replication;DNA replication, synthesis of RNA primer;response to UV;translesion synthesis;replication fork processing
• Cellular component: nucleus;mitochondrial matrix
• Molecular function: chromatin binding;DNA-directed DNA polymerase activity;DNA primase activity;protein binding;manganese ion binding