COPS2

Chr 15

COP9 signalosome subunit 2

Also known as: ALIEN, CSN2, SGN2, TRIP15

NCBI Gene: 9318 ENSG00000166200 UniProt: P61201 OMIM: 604508

Predicted to enable transcription corepressor activity. Involved in protein deneddylation and protein phosphorylation. Located in cytoplasm; intercellular bridge; and nucleus. Part of COP9 signalosome. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 5.04

OE 0.00 (0.00–0.10)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

4.13Z-score

OE missense 0.22 (0.17–0.28)

48 obs / 220.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.10)

0≤0.351.4

Missense OE?0.22 (0.17–0.28)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 0 / 29.6Missense obs/exp: 48 / 220.7Syn Z: 0.75

Background carrier burden — how many people carry a rare variant somewhere in COPS2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 680

239 rare PASS variants

Rare truncating (LoF)

1 in 4,500

25 rare PASS variants

Rare synonymous (reference)

1 in 400

190 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COPS2. 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 710	1 in 5,600
South Asian	~43k	1 in 1,400	1 in 1,100
Remaining (unassigned)	~30k	1 in 1,000	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,500	none seen
Admixed American	~22k	1 in 960	≈ 1 in 7,200
African / African American	~21k	1 in 660	≈ 1 in 17,000
East Asian	~20k	1 in 1,000	none seen
Ashkenazi Jewish	~13k	1 in 610	none seen
Middle Eastern	~2,884	≈ 1 in 2,900	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): 7 of 13 coding exons well covered in gnomAD exomes; exons 2, 3, 4, 10, 11, 12 marginal. Genomes: all 13.? see exons ↓