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.

not_provided (158 variants)
not_specified (25 variants)
Combined_immunodeficiency_due_to_GINS1_deficiency (5 variants)
GINS1-related_disorder (4 variants)
See_cases (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. These statistics are base on transcript: NM_000021067.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	26 clinvar		28
missense		2 clinvar	91 clinvar		1 clinvar	94
nonsense			4 clinvar			4
start loss			1			1
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	2	108	26	1

Highest pathogenic variant AF is 0.00065956736

Loading clinvar variants...

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