CRTC1

Chr 19

CREB regulated transcription coactivator 1

Also known as: MAML2, MECT1, Mam-2, TORC-1, TORC1, WAMTP1

The protein functions as a transcriptional coactivator for CREB1, activating transcription through cAMP response elements and regulating CREB-activated genes involved in metabolism, circadian rhythms, and synaptic plasticity. Mutations cause mucoepidermoid salivary gland carcinoma through a loss-of-function mechanism, though the inheritance pattern is not specified in the available data. The protein is intolerant to loss-of-function variants (LOEUF 0.418), suggesting haploinsufficiency may be pathogenic.

Summary from RefSeq, OMIM, UniProt, Mechanism

Primary Disease Associations & Inheritance

Mucoepidermoid salivary gland carcinoma
0
Active trials
52
Pubs (1 yr)
7
P/LP submissions
0%
P/LP missense
0.42
LOEUF
LOF
Mechanism· predicted
Clinical SummaryCRTC1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 74 VUS of 105 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.531
Z-score 3.89
OE 0.21 (0.120.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.33Z-score
OE missense 0.67 (0.610.75)
274 obs / 405.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.120.42)
00.351.4
Missense OE0.67 (0.610.75)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 6 / 28.3Missense obs/exp: 274 / 405.9Syn Z: -0.53
DN
0.5966th %ile
GOF
0.4677th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.42

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

105 submitted variants in ClinVar

Classification Summary

Pathogenic7
VUS74
Likely Benign6
Benign2
7
Pathogenic
74
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
0
0
0
VUS
0
73
1
0
74
Likely Benign
0
2
0
4
6
Benign
0
0
1
1
2
Total0759589

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

View in ClinVar →

Protein Context — Lollipop Plot

CRTC1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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