GINS1

GINS complex subunit 1, the group of GINS complex

Basic information

Region (hg38): 20:25391008-25452700

Links

ENSG00000101003 ∙ NCBI:9837 ∙ OMIM:610608 ∙ HGNC:28980 ∙ Uniprot:Q14691 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined immunodeficiency due to GINS1 deficiency (Supportive), mode of inheritance: AR
• combined immunodeficiency due to GINS1 deficiency (Limited), mode of inheritance: Unknown
• combined immunodeficiency due to GINS1 deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 55	AR	Allergy/Immunology/Infectious	The condition can include early-onset, severe, and recurrent infections, as well as other immunologic sequelae, and awareness may allow antiinfectious prophylaxis and early and aggressive treatment of infections	Allergy/Immunology/Infectious; Craniofacial; Dermatologic	14702466; 28414293

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GINS1 gene.

• PHARC syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GINS1 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				23		23
missense		1	74		2	77
nonsense			3			3
start loss			1			1
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			4			4
splice region	1		8	4		13
non coding			2	22	2	26
Total	0	1	86	45	4

Variants in GINS1

This is a list of pathogenic ClinVar variants found in the GINS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-25407761-A-G		Combined immunodeficiency due to GINS1 deficiency	Pathogenic (Jan 10, 2018)
20-25407773-C-G		Combined immunodeficiency due to GINS1 deficiency	Uncertain significance (Nov 22, 2023)
20-25407821-A-G			Uncertain significance (Feb 05, 2024)
20-25407824-T-A			Uncertain significance (May 29, 2024)
20-25407826-C-G			Uncertain significance (Dec 10, 2023)
20-25407836-G-T		not specified	Uncertain significance (Sep 14, 2022)
20-25407839-A-G			Uncertain significance (May 13, 2024)
20-25407840-T-C		not specified	Uncertain significance (Oct 22, 2024)
20-25407845-C-T			Likely benign (Feb 06, 2024)
20-25407849-T-G			Uncertain significance (Oct 27, 2024)
20-25407852-G-A			Uncertain significance (Jul 17, 2024)
20-25407863-C-A			Uncertain significance (May 05, 2023)
20-25407872-G-CA		Combined immunodeficiency due to GINS1 deficiency	Uncertain significance (Aug 30, 2019)
20-25407876-G-A			Uncertain significance (Apr 25, 2022)
20-25407883-G-A			Likely benign (May 12, 2022)
20-25407887-G-A		not specified	Uncertain significance (Oct 30, 2024)
20-25407893-A-G		not specified	Uncertain significance (Mar 24, 2023)
20-25407901-G-A			Uncertain significance (May 10, 2022)
20-25413772-T-C			Likely benign (Jun 20, 2024)
20-25413773-C-T			Likely benign (Sep 01, 2022)
20-25413774-G-A			Likely benign (Aug 04, 2023)
20-25413775-G-A			Likely benign (Dec 11, 2023)
20-25413787-T-C			Uncertain significance (Jun 28, 2024)
20-25413795-T-C			Likely benign (Jun 29, 2021)
20-25413799-C-T			Uncertain significance (Nov 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GINS1	protein_coding	protein_coding	ENST00000262460	7	44902

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.70e-7	0.502	125731	0	16	125747	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.221	101	107	0.940	0.00000561	1261
Missense in Polyphen		36	40.249	0.89444		434
Synonymous	-0.490	41	37.2	1.10	0.00000167	363
Loss of Function	0.799	11	14.3	0.772	8.43e-7	157

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000470	0.0000462
European (Non-Finnish)	0.0000622	0.0000615
Middle Eastern	0.000163	0.000163
South Asian	0.000134	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex seems to bind preferentially to single-stranded DNA. {ECO:0000269|PubMed:17417653, ECO:0000269|PubMed:28414293}.
• Disease: DISEASE: Immunodeficiency 55 (IMD55) [MIM:617827]: An autosomal recessive primary immunodeficiency characterized by chronic neutropenia, natural killer cell deficiency, recurrent viral and bacterial infections, and intrauterine growth retardation. Postnatal growth retardation is present in most patients. {ECO:0000269|PubMed:28414293}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Unwinding of DNA;DNA Replication;DNA strand elongation;Synthesis of DNA;S Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.598
• rvis_EVS: 0.3
• rvis_percentile_EVS: 72.01

Haploinsufficiency Scores

• pHI: 0.0920
• hipred: Y
• hipred_score: 0.800
• ghis: 0.632

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.438

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gins1
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype

Gene ontology

• Biological process: inner cell mass cell proliferation;DNA strand elongation involved in DNA replication;DNA duplex unwinding;DNA strand elongation involved in mitotic DNA replication
• Cellular component: GINS complex;nucleus;nucleoplasm;cytoplasm
• Molecular function: 3'-5' DNA helicase activity