CRTC1
protein-codingCREB regulated transcription coactivator 1
Gene summary
Enables cAMP response element binding protein binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Jun 2026]
- MECT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~98.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CRTC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015321.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 4 | 1 | 9 | ||
| missense | 72 | 2 | 74 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 82 | 6 | 1 | 89 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056136.2 | 14 | MANE Select | |
| Ensembl | ENSP00000323332.7 | 14 | MANE Select | |
| RefSeq | NP_001091952.1 | 15 | Standard | |
| Ensembl | ENSP00000345001.5 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HTLV-I infection - Homo sapiens (human)
- Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
- Mesodermal Commitment Pathway
- AP-1 transcription factor network
Biological Process
- memory
- viral process
- positive regulation of CREB transcription factor activity
- entrainment of circadian clock by photoperiod
- positive regulation of transcription by RNA polymerase II
Molecular Function
- protein binding
- cAMP response element binding protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338797
- Coding exons
- 15
- Length
- 98518
- Individuals with no LoFs
- 125663
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 125688
- p
- 0.0000995
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.33 | 274 | 406 | 0.675 | 0.0000260 | 4150 |
| Missense (PolyPhen) | 79 | 150.01 | 0.52664 | 1567 | ||
| Synonymous | -0.534 | 205 | 196 | 1.05 | 0.0000149 | 1370 |
| Loss of Function | 3.89 | 6 | 28.3 | 0.212 | 0.00000130 | 305 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells. In the hippocampus, involved in late- phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. May be required for dendritic growth of developing cortical neurons (By similarity). In concert with SIK1, regulates the light-induced entrainment of the circadian clock. In response to light stimulus, coactivates the CREB-mediated transcription of PER1 which plays an important role in the photic entrainment of the circadian clock. {ECO:0000250|UniProtKB:Q157S1, ECO:0000250|UniProtKB:Q68ED7, ECO:0000269|PubMed:23699513}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving CRTC1 is found in mucoepidermoid carcinomas, benign Warthin tumors and clear cell hidradenomas. Translocation t(11;19)(q21;p13) with MAML2. The fusion protein consists of the N-terminus of CRTC1 joined to the C-terminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the C-terminus of CRTC1 has been detected in a small number of mucoepidermoid carcinomas.;
Recessive Scores
- pRec
- 0.230
Intolerance Scores
- LoFtool
- 0.193
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.917
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |