CRTC3

Chr 15

CREB regulated transcription coactivator 3

Also known as: TORC-3, TORC3

NCBI Gene: 64784ENSG00000140577UniProt: Q6UUV7

This gene is a member of the CREB regulated transcription coactivator gene family. This family regulates CREB-dependent gene transcription in a phosphorylation-independent manner and may be selective for cAMP-responsive genes. The protein encoded by this gene may induce mitochondrial biogenesis and attenuate catecholamine signaling in adipose tissue. A translocation event between this gene and Notch coactivator mastermind-like gene 2, which results in a fusion protein, has been reported in mucoepidermoid carcinomas. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

146
ClinVar variants
39
Pathogenic / LP
0.87
pLI score
0
Active trials
Clinical Summary— CRTC3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 84 VUS of 146 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.36LOEUF
pLI 0.866
Z-score 4.35
OE 0.18 (0.10–0.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.40Z-score
OE missense 0.94 (0.86–1.03)
327 obs / 348.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.10–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.86–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.26
0≤1.21.6
LoF obs/exp: 6 / 33.0Missense obs/exp: 327 / 348.0Syn Z: -2.43

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic4
VUS84
Likely Benign5
Benign2
Conflicting1
35
Pathogenic
4
Likely Pathogenic
84
VUS
5
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
4
0
4
VUS
0
80
4
0
84
Likely Benign
0
4
0
1
5
Benign
0
0
0
2
2
Conflicting
—1
Total084433131

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

View in ClinVar →

Protein Context — Lollipop Plot

CRTC3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dasatinib Stimulates Its Own Mechanism of Resistance by Activating a CRTC3/MITF/Bcl-2 Pathway in Melanoma with Mutant or Amplified c-Kit.
Sabbah M et al.·Mol Cancer Res
2021Functional
Long read sequencing identifies complex structural variant landscape and recurrent TERT rearrangements in mucoepidermoid carcinoma.
Gensterblum-Miller E et al.·Oral Oncol
2024
Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma.
Nakayama T et al.·Mod Pathol
2009
A novel fusion gene CRTC3-MAML2 in hidradenoma: histopathological significance.
Kuma Y et al.·Hum Pathol
2017
CRTC3 links catecholamine signalling to energy balance.
Song Y et al.·Nature
2010
A new type of MAML2 fusion in mucoepidermoid carcinoma.
Fehr A et al.·Genes Chromosomes Cancer
2008
Appraising the life-course impact of Epstein-Barr virus exposure and its genetic signature on periodontitis.
Ye X et al.·J Periodontol
2025
Cyclic adenosine monophosphate-regulated transcriptional co-activator 3 polymorphism in Chinese patients with acute coronary syndrome.
Zhu L et al.·Medicine (Baltimore)
2018Cohort
Impact of CRTC1/3-MAML2 fusions on histological classification and prognosis of mucoepidermoid carcinoma.
Okumura Y et al.·Histopathology
2011
Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma.
Noda H et al.·Cancer Sci
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools