PRIM1

DNA primase subunit 1

Basic information

Region (hg38): 12:56730437-56752374

Links

ENSG00000198056 ∙ NCBI:5557 ∙ OMIM:176635 ∙ HGNC:9369 ∙ Uniprot:P49642 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primordial dwarfism-immunodeficiency-lipodystrophy syndrome (Limited), mode of inheritance: AR
• primordial dwarfism-immunodeficiency-lipodystrophy syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Primordial dwarfism-immunodeficiency-lipodystrophy syndrome	AR	Allergy/Immunology/Infectious	Among other findings, the condition can include immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Pulmonary	33060134

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRIM1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRIM1 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						0
missense			15	2	1	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding						0
Total	0	1	15	2	1

Variants in PRIM1

This is a list of pathogenic ClinVar variants found in the PRIM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-56731723-C-A		not specified	Uncertain significance (May 23, 2023)
12-56731730-T-G		not specified	Uncertain significance (May 02, 2024)
12-56734173-C-T		not specified	Uncertain significance (Jan 26, 2022)
12-56734200-T-C		not specified	Uncertain significance (Jun 07, 2024)
12-56738452-C-T			Likely benign (Nov 01, 2023)
12-56738514-C-T		not specified	Likely benign (Dec 19, 2023)
12-56738515-G-A		not specified	Uncertain significance (May 18, 2023)
12-56740091-G-A			Likely benign (Jul 01, 2024)
12-56741516-A-G		Primordial dwarfism-immunodeficiency-lipodystrophy syndrome • Microcephalic primordial dwarfism	Pathogenic (Aug 12, 2022)
12-56741544-C-A		Premature ovarian failure	Uncertain significance (Mar 02, 2020)
12-56741751-A-C		not specified	Uncertain significance (Jan 22, 2024)
12-56741784-G-A		not specified	Uncertain significance (Mar 29, 2022)
12-56744029-G-C		Microcephalic primordial dwarfism • Primordial dwarfism-immunodeficiency-lipodystrophy syndrome	Pathogenic (Aug 12, 2022)
12-56744074-G-A		not specified	Uncertain significance (Aug 19, 2023)
12-56744111-C-T		not specified	Uncertain significance (Mar 24, 2023)
12-56746113-C-T		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
12-56746131-C-T		not specified	Uncertain significance (Jan 04, 2022)
12-56746169-A-C		not specified	Uncertain significance (Jan 19, 2022)
12-56746795-T-C		not specified	Uncertain significance (Sep 29, 2023)
12-56746945-C-T		not specified	Uncertain significance (Jan 18, 2023)
12-56752194-A-C			Likely pathogenic (Jul 01, 2022)
12-56752195-C-A		Primordial dwarfism-immunodeficiency-lipodystrophy syndrome • Microcephalic primordial dwarfism	Pathogenic (Aug 12, 2022)
12-56752201-C-T		not specified	Uncertain significance (Aug 15, 2023)
12-56752219-T-C		not specified	Uncertain significance (Jan 18, 2023)
12-56752228-G-C		not specified	Uncertain significance (Oct 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRIM1	protein_coding	protein_coding	ENST00000338193	13	20778

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000994	0.997	124653	0	17	124670	0.0000682

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.05	122	204	0.597	0.0000103	2788
Missense in Polyphen		28	62.372	0.44892		801
Synonymous	0.741	57	64.6	0.883	0.00000310	677
Loss of Function	2.67	9	22.8	0.395	0.00000104	314

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000582	0.0000582
Ashkenazi Jewish	0.000411	0.000397
East Asian	0.0000558	0.0000556
Finnish	0.0000929	0.0000928
European (Non-Finnish)	0.0000782	0.0000708
Middle Eastern	0.0000558	0.0000556
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);DNA replication - Homo sapiens (human);Purine metabolism - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;Retinoblastoma (RB) in Cancer;Pyrimidine metabolism;G1 to S cell cycle control;DNA Replication;Inhibition of replication initiation of damaged DNA by RB1/E2F1;Polymerase switching on the C-strand of the telomere;Activation of the pre-replicative complex;E2F mediated regulation of DNA replication;Mitotic G1-G1/S phases;DNA replication initiation;DNA Replication;Polymerase switching;Leading Strand Synthesis;Removal of the Flap Intermediate;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;S Phase;Telomere C-strand synthesis initiation;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;G1/S Transition;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Intolerance Scores

• loftool: 0.636
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.958
• hipred: Y
• hipred_score: 0.772
• ghis: 0.638

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prim1

Zebrafish Information Network

• Gene name: prim1
• Affected structure: cranial cartilage
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication, synthesis of RNA primer;telomere maintenance via semi-conservative replication
• Cellular component: nucleoplasm;alpha DNA polymerase:primase complex;membrane
• Molecular function: single-stranded DNA binding;DNA primase activity;metal ion binding