CRTC3

Chr 15

CREB regulated transcription coactivator 3

Also known as: TORC-3, TORC3

NCBI Gene: 64784ENSG00000140577UniProt: Q6UUV7OMIM: 608986

The CRTC3 protein functions as a transcriptional coactivator for CREB1, activating cAMP-responsive genes and inducing mitochondrial biogenesis in muscle cells. This gene is highly constrained against loss-of-function variants (pLI=0.87, LOEUF=0.36), but no Mendelian diseases have been definitively associated with CRTC3 mutations in current databases. While chromosomal translocations involving CRTC3 have been reported in mucoepidermoid carcinomas, germline variants causing pediatric neurological disorders have not been established.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.36
Clinical Summary— CRTC3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 73 VUS of 100 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
0.40Z-score
OE missense 0.94 (0.86–1.03)
327 obs / 348.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.10–0.36)
0≤0.351.4
Missense OE0.94 (0.86–1.03)
0≤0.61.4
Synonymous OE1.26
0≤1.21.6
LoF obs/exp: 6 / 33.0Missense obs/exp: 327 / 348.0Syn Z: -2.43
DN
0.4983th %ile
GOF
0.3788th %ile
LOF
0.75top 10%

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

LOFprediction above median · LOEUF 0.36

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

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS73
Likely Benign5
Conflicting1
4
Pathogenic
2
Likely Pathogenic
73
VUS
5
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
2
0
2
VUS
0
71
2
0
73
Likely Benign
0
4
0
1
5
Benign
0
0
0
0
0
Conflicting
—1
Total0758185

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients