COPS7B

Chr 2

COP9 signalosome subunit 7B

Also known as: CSN7B, SGN7b

The COPS7B protein is a component of the COP9 signalosome complex that regulates protein degradation by removing nedd8 modifications from cullin proteins in E3 ubiquitin ligase complexes. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia, seizures, and brain abnormalities including delayed myelination and corpus callosum abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.488), consistent with its essential role in cellular protein regulation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
30
P/LP submissions
0%
P/LP missense
0.49
LOEUF
Mechanism
Clinical SummaryCOPS7B
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 30 VUS of 65 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.601
Z-score 2.99
OE 0.19 (0.090.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.09Z-score
OE missense 0.75 (0.640.88)
108 obs / 144.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.090.49)
00.351.4
Missense OE0.75 (0.640.88)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 3 / 15.9Missense obs/exp: 108 / 144.8Syn Z: 0.27

ClinVar Variant Classifications

65 submitted variants in ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic1
VUS30
29
Pathogenic
1
Likely Pathogenic
30
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
1
0
1
VUS
0
26
4
0
30
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02634060

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

View in ClinVar →

Protein Context — Lollipop Plot

COPS7B · 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.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC