Alt. symbols: KIAA0186 | PSF1

Approved name: GINS complex subunit 1
Alt. names: GINS complex subunit 1 (Psf1 homolog)

Location: 20p11.21: 25391008 - 25452700 (+)
Gene type: protein_coding, 25 transcripts.

Scores: LoFtool: 0.598000 | pLI: 0.05003698 | LOEUF: 1.277

HGNC: 28980

NCBI: 9837, RefSeq: .0

Ensembl: ENSG00000101003.12

LRG_ | Status: none

OMIM: 610608

Expression | ProteinAtlas

The gene GINS1 encodes a subunit of the heterotetrameric protein complex GINS, which plays a role in the initiation and elongation stages of eukaryotic DNA replication. First described in the yeast Saccaromyces cerevisiae, the GINS complex is composed of four subunits Sld5 (GINS4), Psf1 (GINS1), Psf2 (GINS2), and Psf3 (GINS3), which are all conserved among eukaryotes. The GINS complex is found to be a component of the replicative helicase machinery and holds a key role in DNA replication by establishing the initiation complex after pre-replicative complex assembly. After maturation, this complex ensures the initiation of DNA synthesis.

Mutations in GINS1 have been associated with immunodeficiency 55, an autosomal recessive immunodeficiency characterized by intrauterine and postnatal growth retardation, chronic neutropenia and natural killer (NK) cell deficiency, which is caused by a defect in DNA replication that prevents immune cell differentiation in the bone marrow, especially affecting differentiation of NK cells. Further clinical manifestations are mild facial dysmorphism, eczema as well as recurrent viral and bacterial i nfections. Whole exome sequencing analysis of five immunodeficiency-55 patients from four unrelated families resulted in the identification of compound heterozygous mutations in GINS1 (Cottineau et al., 2017). Two of the variants that resulted in altered splicing events (c.-60A>G, c.-48C>G) were found in the 5'UTR in exon 1, whereas two missense variants were found in exon 4 (R83C) and exon 6 (C152Y), respectively. In compound heterozygosity of either one of the splicing variants with the R83C missense variant or the c.-48C>G splicing variant with the C152Y missense variant, GINS1 protein levels in the patients cells were shown to be decreased and GINS complex assembly was impaired, which resulted in replication stress. In contrast, heterozygous carriers in the families were not affected. [Load More]