COPS8

Chr 2

COP9 signalosome subunit 8

Also known as: COP9, CSN8, SGN8

The COPS8 protein is a subunit of the COP9 signalosome complex that regulates ubiquitin-mediated protein degradation by controlling E3 ligase activity and phosphorylating key cellular proteins including p53. The gene is highly constrained against loss-of-function variants (LOEUF 0.486), but specific diseases associated with COPS8 mutations have not been established in the current literature. Inheritance pattern for potential COPS8-related disorders remains to be determined.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
74
P/LP submissions
0%
P/LP missense
0.49
LOEUF
Mechanism
Clinical SummaryCOPS8
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 34 VUS of 121 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.725
Z-score 2.82
OE 0.15 (0.060.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.92Z-score
OE missense 0.76 (0.640.91)
87 obs / 114.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.060.49)
00.351.4
Missense OE0.76 (0.640.91)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 2 / 13.0Missense obs/exp: 87 / 114.7Syn Z: 0.04

ClinVar Variant Classifications

121 submitted variants in ClinVar

Classification Summary

Pathogenic73
Likely Pathogenic1
VUS34
73
Pathogenic
1
Likely Pathogenic
34
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
73
0
73
Likely Pathogenic
0
0
1
0
1
VUS
0
27
7
0
34
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total027810108

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

View in ClinVar →

Protein Context — Lollipop Plot

COPS8 · 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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