CCAR2

Chr 8

cell cycle and apoptosis regulator 2

Also known as: DBC-1, DBC1, KIAA1967, NET35, p30 DBC, p30DBC

CCAR2 encodes a core component of the DBIRD complex that regulates RNA polymerase II transcript elongation and alternative splicing, while also functioning as an inhibitor of multiple enzymes including SIRT1 deacetylase and playing roles in DNA damage response and circadian regulation. The gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.32), but associated human diseases from mutations in CCAR2 have not yet been established in the medical literature.

Summary from RefSeq, UniProt
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0
Active trials
12
Pubs (1 yr)
83
P/LP submissions
0%
P/LP missense
0.32
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryCCAR2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
83 unique Pathogenic / Likely Pathogenic· 153 VUS of 282 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.941
Z-score 5.27
OE 0.19 (0.110.32)
Highly constrained

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

Missense Constraint
0.73Z-score
OE missense 0.91 (0.850.98)
498 obs / 546.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.110.32)
00.351.4
Missense OE0.91 (0.850.98)
00.61.4
Synonymous OE1.31
01.21.6
LoF obs/exp: 9 / 48.6Missense obs/exp: 498 / 546.2Syn Z: -3.66
DN
0.2599th %ile
GOF
0.2597th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.32

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

282 submitted variants in ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic4
VUS153
Likely Benign28
Benign14
Conflicting1
79
Pathogenic
4
Likely Pathogenic
153
VUS
28
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
4
0
4
VUS
0
146
7
0
153
Likely Benign
1
7
5
15
28
Benign
0
2
3
9
14
Conflicting
1
Total11559824279

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

View in ClinVar →

Protein Context — Lollipop Plot

CCAR2 · 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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