COPS4

Chr 4

COP9 signalosome subunit 4

Also known as: CSN4, SGN4

This gene encodes a subunit of the COP9 signalosome complex, which regulates protein degradation pathways by controlling the activity of E3 ubiquitin ligases and mediating deneddylation of cullin proteins. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation. The gene is highly constrained against loss-of-function variants in the population, indicating that complete loss of function is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
36
P/LP submissions
0%
P/LP missense
0.20
LOEUF· LoF intol.
Mechanism
Clinical SummaryCOPS4
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 21 VUS of 77 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.20LOEUF
pLI 0.999
Z-score 4.36
OE 0.04 (0.010.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.14Z-score
OE missense 0.40 (0.340.48)
88 obs / 218.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.04 (0.010.20)
00.351.4
Missense OE0.40 (0.340.48)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 1 / 24.1Missense obs/exp: 88 / 218.4Syn Z: -1.21

ClinVar Variant Classifications

77 submitted variants in ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic3
VUS21
33
Pathogenic
3
Likely Pathogenic
21
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
3
0
3
VUS
0
18
3
0
21
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total01839057

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

COPS4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found