GINS4

Chr 8

GINS complex subunit 4

Also known as: SLD5

NCBI Gene: 84296 ENSG00000147536 UniProt: Q9BRT9 OMIM: 610611

The yeast heterotetrameric GINS complex is made up of Sld5, Psf1 (GINS1; MIM 610608), Psf2 (GINS2; MIM 610609), and Psf3 (GINS3; MIM 610610). The formation of the GINS complex is essential for the initiation of DNA replication in yeast and Xenopus egg extracts (Ueno et al., 2005 [PubMed 16287864]). See GINS1 for additional information about the GINS complex.[supplied by OMIM, Mar 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · combined immunodeficiency · AR · ClinGen 2026

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.07

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.37

OE 0.60 (0.35–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.54Z-score

OE missense 0.87 (0.74–1.01)

111 obs / 128.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.35–1.07)

0≤0.351.4

Missense OE?0.87 (0.74–1.01)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 8 / 13.4Missense obs/exp: 111 / 128.2Syn Z: 1.10

Background carrier burden — how many people carry a rare variant somewhere in GINS4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

263 rare PASS variants

Rare truncating (LoF)

1 in 2,200

50 rare PASS variants

Rare synonymous (reference)

1 in 700

92 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GINS4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 390	1 in 2,600
South Asian	~43k	1 in 150	1 in 770
Remaining (unassigned)	~30k	1 in 210	1 in 1,900
European (Finnish)	~27k	1 in 1,200	≈ 1 in 13,000
Admixed American	~22k	1 in 340	1 in 1,400
African / African American	~21k	1 in 180	1 in 2,000
East Asian	~20k	1 in 320	1 in 3,300
Ashkenazi Jewish	~13k	1 in 2,200	none seen
Middle Eastern	~2,884	1 in 410	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 7 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 7.? see exons ↓