CRTC1

Summary

CRTC1 (CREB regulated transcription coactivator 1, HGNC:16062) is a protein-coding gene on chromosome 19p13.11, encoding CREB-regulated transcription coactivator 1 (Q6UUV9). Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites.

Enables cAMP response element binding protein binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol; nuclear body; and plasma membrane.

Source: NCBI Gene 23373 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 97 total
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_015321

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16062
Approved symbol	CRTC1
Name	CREB regulated transcription coactivator 1
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0616, FLJ14027, TORC1
Ensembl gene	ENSG00000105662
Ensembl biotype	protein_coding
OMIM	607536
Entrez	23373

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000321949, ENST00000338797, ENST00000594658, ENST00000601916, ENST00000862461, ENST00000862462, ENST00000862463, ENST00000862464, ENST00000862465, ENST00000862466, ENST00000862467, ENST00000862468, ENST00000862469, ENST00000862470, ENST00000862471, ENST00000862472, ENST00000862473, ENST00000862474, ENST00000929717, ENST00000929718

RefSeq mRNA: 2 — MANE Select: NM_015321 NM_001098482, NM_015321

CCDS: CCDS32963, CCDS42525

Canonical transcript exons

ENST00000321949 — 14 exons

Exon	Start	End
ENSE00000690330	18771442	18771546
ENSE00000690331	18774900	18774986
ENSE00000690332	18775641	18775821
ENSE00000866194	18753500	18753585
ENSE00000866196	18749781	18749875
ENSE00001113513	18760008	18760228
ENSE00001113514	18765404	18765528
ENSE00001113515	18768485	18768793
ENSE00001401208	18759551	18759591
ENSE00001504871	18747053	18747114
ENSE00001504872	18745823	18745960
ENSE00001549009	18777171	18782333
ENSE00003001563	18683680	18683828
ENSE00003590654	18742910	18743026

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 96.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3678 / max 194.7216, expressed in 1679 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174722	5.3447	1623
174718	0.3820	126
174719	0.2654	92
174720	0.1360	47
174717	0.1063	42
174721	0.0966	36
174723	0.0369	10

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	96.74	silver quality
type B pancreatic cell	CL:0000169	96.43	silver quality
paraflocculus	UBERON:0005351	95.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.01	gold quality
cerebellar hemisphere	UBERON:0002245	94.25	gold quality
cerebellar cortex	UBERON:0002129	94.23	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.79	gold quality
cerebellum	UBERON:0002037	93.59	gold quality
middle frontal gyrus	UBERON:0002702	93.29	gold quality
frontal pole	UBERON:0002795	92.82	gold quality
cerebellar vermis	UBERON:0004720	92.41	gold quality
right frontal lobe	UBERON:0002810	92.14	gold quality
endometrium epithelium	UBERON:0004811	91.65	silver quality
nucleus accumbens	UBERON:0001882	90.27	gold quality
cingulate cortex	UBERON:0003027	90.22	gold quality
anterior cingulate cortex	UBERON:0009835	90.15	gold quality
prefrontal cortex	UBERON:0000451	89.02	gold quality
triceps brachii	UBERON:0001509	88.97	silver quality
frontal cortex	UBERON:0001870	88.83	gold quality
amygdala	UBERON:0001876	88.82	gold quality
neocortex	UBERON:0001950	88.62	gold quality
putamen	UBERON:0001874	88.41	gold quality
gluteal muscle	UBERON:0002000	88.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.11	gold quality
caudate nucleus	UBERON:0001873	88.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.97	gold quality
telencephalon	UBERON:0001893	87.21	gold quality
cerebral cortex	UBERON:0000956	87.15	gold quality
orbitofrontal cortex	UBERON:0004167	87.10	gold quality
brain	UBERON:0000955	87.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.25

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PPARGC1A	Activation

Upstream regulators (CollecTRI, top): CREB1, NCOR1, NFATC4, RBPJ

Literature-anchored findings (GeneRIF, showing 40)

• cloning and functional analyses of the t(11;19) fusion oncogene: t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. (PMID:12539049)
• cloning of a novel fusion gene in mucoepidermoid carcinomas & benign Warthin’s tumors; the fusion, which results from a translocation, creates a chimeric gene in which exon 1 of a novel gene designated WAMTP1 is linked to exons 2-5 of MAML2 [WAMPT1] (PMID:14720503)
• mutant Mect1-Maml2 expression plasmid carried silent nucleotide changes within the RNAi target sequence and observed that co-transfection of this mutant, but not wild-type Mect1-Maml2, could partially rescue RNAi growth inhibition in the MEC tumor line (PMID:16652146)
• Thus, both TORC1/2 and p300 families of coactivators are essential for optimal activation of HTLV-1 transcription by Tax. (PMID:16809310)
• The MECT1-MAML2 fusion transcript may be specific to mucoepidermoid carcinoma and associated with a distinct mucoepidermoid carcinoma subset that exhibits favorable clinicopathologic features and an indolent clinical course. (PMID:16818685)
• These results strongly suggest that TORCs play a key role in linking these external signals to the transcriptional program of adaptive mitochondrial biogenesis by activating PGC-1alpha gene transcription. (PMID:16980408)
• The present and previous observations indicate that the CRTC1-MAML2 fusion is etiologically linked to benign and low-grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity. (PMID:17334997)
• CRTC1/MAML2 transcript may be detected in both low and high grade mucoepidermoid carcinoma (MEC), that fusion negative tumors may define a subset of biologically aggressive MEC’s tumors (PMID:17437281)
• the basic leucine zipper domain has a role in the regulation of transcriptional activity of CREB with TORC and salt inducible kinase [review] (PMID:17565599)
• CRTC1/MAML2 translocation and fusion transcript is asscociated with Warthin’s tumor and mucoepidermoid carcinoma (PMID:18181164)
• The presence of the t(11;19)(q21;p13) rearrangement favors a diagnosis of mucoepidermoid carcinoma. (PMID:18206539)
• Stimulation by lithium of the interaction between CREB and TORC1 is reported. (PMID:18717645)
• The activation of TORC1 through MEKK1-mediated phosphorylation, is reported. (PMID:18784253)
• demonstrate that CRTC1-Maml2 oncoprotein, which causes mucoepidermoid carcinomas, binds and activates both c-Jun and c-Fos. (PMID:19164581)
• MAML2 and MECT1 fusion product can be detected by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction analysis performed on low- and high-grade primary bronchopulmonary mucoepidermoid carcinoma (PMID:19269006)
• Mucoepidermoid carcinoma (MEC) of the skin harbours CRTC1 rearrangements, a molecular finding that reflects morphological similarities between glandular and cutaneous MEC. (PMID:19438452)
• Mucoepidermoid carcinomas are often characterized by the fusion gene CRTC1-MAML2. The mean expression level of an embryonic stem cell marker, HMGA2 was studied and found to be higher in fusion negative than in positive tumors. (PMID:19521953)
• CRTC1-MAML2 fusion was associated with favorable clinicopathologic tumor features and was useful in predicting the overall survival of patients with salivary gland mucoepidermoid carcinoma (PMID:19531414)
• Data show that somatic loss of LKB1 is associated with underphosphorylation of endogenous Crtc1, enhanced Crtc1 nuclear localization. (PMID:20010869)
• MECT1/MAML2 translocation status may be important prognostically in salivary mucoepidermoid carcinomas, but it does not seem to override traditional clinicopathologic parameters. (PMID:20588178)
• We report an example of intraosseous mucoepidermoid carcinoma with positive TORC1/MAML2 gene fusion transcript and discuss the clinical implications. (PMID:20625861)
• The t(11;19) translocation and its CRTC1/MAML1 fusion transcript have been identified in mucoepidermoid carcinomas at different sites and are believed to be associated with the development of a subset of these tumors. (PMID:21074686)
• mucoepidermoid carcinoma of the salivary glands positive for CRTC1-MAML2 or CRTC3-MAML2 fusion formed a favourable tumour subset that was distinct from fusion-negative cases (PMID:21668476)
• de-regulated LKB1-CRTC signaling might represent a crucial mechanism for esophageal cancer progression. (PMID:21706049)
• clear-cell renal cell carcinoma become refractory to REDD1-induced mTORC1 inhibition and shed light into the development of clear-cell renal cell carcinoma (PMID:21798997)
• The results of this study suggested that CRTC1 dysfunction caused by Abeta accumulation underlies changes in gene expression required for hippocampal-dependent memory in AD transgenic mice. (PMID:22236576)
• Studies indicate that phospholipase D (PLD) as a mediator of nutrients to mTORC1. (PMID:22457329)
• Inhibition of TORC1 retards, and to some extent reverses, phenotypic indicators of cellular senescence. (PMID:22627671)
• We demonstrate that glutamine in combination with leucine activates mammalian TORC1 (mTORC1) by enhancing glutaminolysis and alpha-ketoglutarate production. (PMID:22749528)
• These observations indicate that brain malformations in TSC are likely a consequence of increased TORC1 activation during embryonic brain development. (PMID:22805177)
• CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss. (PMID:23074285)
• The data of this study raise the prospect that CRTC1 plays a role in fundamental aspects of SCN clock timing and entrainment. (PMID:23699513)
• findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. (PMID:23925723)
• aberrantly activated AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and survival, suggesting that EGFR-targeted therapies will benefit patients with advanced, unresectable CRTC1-MAML2-positive MEC. (PMID:23975434)
• Metaplastic Warthin tumor and metaplastic pleomorphic adenoma of salivary glands did not harbor CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, or MAML2 gene rearrangement. (PMID:24121173)
• Lacrimal and salivary gland PAs and Ca-ex-PAs have similar genomic profiles and frequently overexpress the PLAG1 oncoprotein. Copy number gains involving 9p23-p22.3 (NFIB) and 22q12-qter (PDGFB) may be of importance for disease progression. (PMID:24468654)
• Translocation t(11;19)(q14-21;p12-13) in patients with Salivary mucoepidermoid carcinoma was reported , which results in fusion between exons 1 and 2 of CRTC1 on chromosome 19p13. (PMID:24771140)
• Malignant mucoepidermoid salivary gland tumors can arise from a recurrent t (11, 19)(q21;p13.1) translocation that generates an unusual chimeric CRTC1/MAML2 oncoprotein. (PMID:25071166)
• describe fundamental metabolic requirements of senescent primary human CD8+ T cells and demonstrate that p38 MAPK blockade reverses senescence via an mTOR-independent pathway (PMID:25083993)
• This study showed that CREB-regulated transcriptional coactivator 1 (CRTC1) is required for HBV transcription and replication. (PMID:25300488)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	crtc1a	ENSDARG00000076068
danio_rerio	crtc1b	ENSDARG00000076076
mus_musculus	Crtc1	ENSMUSG00000003575
rattus_norvegicus	Crtc1	ENSRNOG00000022421
drosophila_melanogaster	Crtc	FBGN0036746
caenorhabditis_elegans	crtc-1	WBGENE00021237

Paralogs (2): CRTC3 (ENSG00000140577), CRTC2 (ENSG00000160741)

Protein

Protein identifiers

CREB-regulated transcription coactivator 1 — Q6UUV9 (reviewed: Q6UUV9)

Alternative names: Mucoepidermoid carcinoma translocated protein 1, Transducer of regulated cAMP response element-binding protein 1

All UniProt accessions (3): Q6UUV9, M0QX46, M0QXN6

UniProt curated annotations — full annotation on UniProt →

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. 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. (Microbial infection) Plays a role of coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR).

Subunit / interactions. Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1. ‘Arg-314’ in the bZIP domain of CREB1 is essential for this interaction. Interaction, via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1. Interacts with 14-3-3 proteins, including YWHAE/14-3-3 epsilon. Interacts with calmodulin-dependent catalytic subunit PPP3CA/calcineurin A. (Microbial infection) Interacts with HTLV1 Tax.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in adult and fetal brain. Located to specific regions such as the prefrontal cortex and cerebellum. Very low expression in other tissues such as heart, spleen, lung, skeletal muscle, salivary gland, ovary and kidney.

Post-translational modifications. Phosphorylation/dephosphorylation states of Ser-151 are required for regulating transduction of CREB activity. TORCs are inactive when phosphorylated, and active when dephosphorylated at this site. This primary site of phosphorylation is mediated by SIKs (SIK1 and SIK2), is regulated by cAMP and calcium levels and is dependent on the phosphorylation of SIKs by LKB1.

Disease relevance. 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.

Similarity. Belongs to the TORC family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6UUV9-1	1	yes
Q6UUV9-2	2
Q6UUV9-3	3

RefSeq proteins (2): NP_001091952, NP_056136* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024783	TORC_N	Domain
IPR024784	TORC_M	Domain
IPR024785	TORC_C	Domain
IPR024786	TORC	Family

Pfam: PF12884, PF12885, PF12886

UniProt features (30 total): compositionally biased region 7, modified residue 5, region of interest 4, splice variant 3, sequence variant 3, sequence conflict 3, site 2, chain 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7D8P	X-RAY DIFFRACTION	2
7D9V	X-RAY DIFFRACTION	2.21
7D8H	X-RAY DIFFRACTION	2.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UUV9-F1	52.07	0.05

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 42–43 (breakpoint for translocation to form the mect1-maml2 and maml2-mect1 fusion proteins); 575 (required for ubiquitination and degradation)

Post-translational modifications (5): 64, 113, 149, 151, 161

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-9707616	Heme signaling
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9931510	Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes

MSigDB gene sets: 156 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_MEMORY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_PHOTOPERIODISM, GOBP_POSITIVE_REGULATION_OF_CREB_TRANSCRIPTION_FACTOR_ACTIVITY, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_RESPONSE_TO_CAMP, GOBP_CELLULAR_RESPONSE_TO_CAMP, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_RADIATION

GO Biological Process (9): memory (GO:0007613), obsolete positive regulation of CREB transcription factor activity (GO:0032793), entrainment of circadian clock by photoperiod (GO:0043153), positive regulation of transcription by RNA polymerase II (GO:0045944), rhythmic process (GO:0048511), protein homotetramerization (GO:0051289), cellular response to cAMP (GO:0071320), energy homeostasis (GO:0097009), negative regulation of membrane hyperpolarization (GO:1902631)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), cAMP response element binding protein binding (GO:0008140), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Circadian clock	2
Mitochondrial biogenesis	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
positive regulation of DNA-templated transcription	2
learning or memory	1
photoperiodism	1
entrainment of circadian clock	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
biological_process	1
protein homooligomerization	1
protein tetramerization	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
multicellular organismal-level homeostasis	1
negative regulation of biological process	1
membrane hyperpolarization	1
regulation of membrane hyperpolarization	1
transcription coregulator activity	1
DNA-binding transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRTC1	CREB1	P16220	972
CRTC1	MAML2	Q8IZL2	784
CRTC1	MAML3	Q96JK9	745
CRTC1	MAML1	Q92585	725
CRTC1	SIK2	Q9H0K1	693
CRTC1	SPRED1	Q7Z699	671
CRTC1	NFIB	O00712	576
CRTC1	SIK1	P57059	574
CRTC1	OGT	O15294	548
CRTC1	PLAG1	Q6DJT9	543
CRTC1	CARTPT	Q16568	528
CRTC1	OGA	O60502	528
CRTC1	A0A0B4J2F2	A0A0B4J2F2	520
CRTC1	KISS1	Q15726	517
CRTC1	CRTC3	Q6UUV7	507

IntAct

52 interactions, top by confidence:

A	B	Type	Score
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
MEIS1	CREB1	psi-mi:“MI:0914”(association)	0.680
CREB1	CRTC1	psi-mi:“MI:0915”(physical association)	0.670
CRTC1	YWHAE	psi-mi:“MI:0915”(physical association)	0.650
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
SFN	CRTC1	psi-mi:“MI:0915”(physical association)	0.400
CRTC1		psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAH	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350

BioGRID (57): CRTC1 (Affinity Capture-Western), CRTC1 (Affinity Capture-Western), CRTC1 (Biochemical Activity), CRTC1 (Affinity Capture-MS), CRTC1 (Affinity Capture-MS), CRTC1 (Affinity Capture-MS), CRTC1 (Affinity Capture-MS), CRTC1 (Proximity Label-MS), CREB1 (Two-hybrid), CRTC1 (Proximity Label-MS), CRTC1 (Affinity Capture-MS), CRTC1 (Biochemical Activity), CRTC1 (Affinity Capture-Western), CRTC1 (Affinity Capture-Western), CRTC1 (Proximity Label-MS)

ESM2 similar proteins: O08755, O16011, O43312, O60422, O77638, O88532, O88942, O95948, P0CL69, P17544, P54288, P70512, P98201, Q01826, Q02930, Q08289, Q08DV5, Q13469, Q3UR85, Q5R9C9, Q5REX3, Q5VTB9, Q60591, Q60611, Q6NT76, Q6P1E1, Q6P9S0, Q6PDX6, Q6UFS5, Q6UUV9, Q6XBJ3, Q765P7, Q7TMA2, Q8BIE6, Q8BJA3, Q8C0V0, Q8CIE2, Q8HXD5, Q8K557, Q8NF64

Diamond homologs: Q08E26, Q0IHT3, Q157S1, Q3LRZ1, Q3U182, Q52KS4, Q53ET0, Q68ED7, Q6UUV7, Q6UUV9, Q91X84, Q95XA8

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SIK1	down-regulates	CRTC1	phosphorylation
PRKAA1	down-regulates	CRTC1	phosphorylation
MAP3K1	up-regulates	CRTC1	phosphorylation
SIRT1	up-regulates	CRTC1	deacetylation
AMPK	down-regulates	CRTC1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	213.2×	6e-14
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	188.1×	9e-14
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	188.1×	9e-14
Activation of BH3-only proteins	7	139.0×	9e-13
RHO GTPases activate PKNs	7	88.8×	2e-11
Intrinsic Pathway for Apoptosis	7	82.0×	4e-11
FOXO-mediated transcription	5	67.2×	9e-08
SARS-CoV-1-host interactions	7	49.2×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	75.8×	3e-08
intracellular protein localization	8	28.9×	3e-08

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — ACYC.

Clinical variants and AI predictions

ClinVar

97 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3598 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18683790:G:GT	donor_gain	1.0000
19:18683802:G:GT	donor_gain	1.0000
19:18683825:GCGG:G	donor_gain	1.0000
19:18683827:GG:G	donor_gain	1.0000
19:18683828:GG:G	donor_gain	1.0000
19:18683829:G:GG	donor_gain	1.0000
19:18683830:T:G	donor_loss	1.0000
19:18743023:CCAGG:C	donor_loss	1.0000
19:18743024:CAGG:C	donor_loss	1.0000
19:18743025:AGGT:A	donor_loss	1.0000
19:18743026:GGTG:G	donor_loss	1.0000
19:18743027:GTGA:G	donor_loss	1.0000
19:18753498:A:AG	acceptor_gain	1.0000
19:18753499:G:GA	acceptor_gain	1.0000
19:18759592:G:GG	donor_gain	1.0000
19:18760007:GC:G	acceptor_gain	1.0000
19:18760112:C:CA	acceptor_gain	1.0000
19:18760227:GG:G	donor_gain	1.0000
19:18760228:GG:G	donor_gain	1.0000
19:18765525:TCAGG:T	donor_loss	1.0000
19:18765527:AGG:A	donor_loss	1.0000
19:18765528:GG:G	donor_loss	1.0000
19:18765529:GTGCG:G	donor_loss	1.0000
19:18768059:GA:G	donor_gain	1.0000
19:18771547:G:GG	donor_gain	1.0000
19:18774899:GCACA:G	acceptor_gain	1.0000
19:18775639:A:AG	acceptor_gain	1.0000
19:18775639:AGCT:A	acceptor_gain	1.0000
19:18775639:AGCTG:A	acceptor_gain	1.0000
19:18775640:G:GT	acceptor_gain	1.0000

AlphaMissense

4111 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18683724:C:T	R8W	1.000
19:18683727:A:G	K9E	1.000
19:18683730:T:C	F10L	1.000
19:18683730:T:G	F10V	1.000
19:18683731:T:C	F10S	1.000
19:18683731:T:G	F10C	1.000
19:18683732:C:A	F10L	1.000
19:18683732:C:G	F10L	1.000
19:18683733:A:C	S11R	1.000
19:18683735:C:A	S11R	1.000
19:18683735:C:G	S11R	1.000
19:18683736:G:A	E12K	1.000
19:18683737:A:T	E12V	1.000
19:18683741:G:C	K13N	1.000
19:18683741:G:T	K13N	1.000
19:18683743:T:A	I14N	1.000
19:18683743:T:C	I14T	1.000
19:18683743:T:G	I14S	1.000
19:18683745:G:C	A15P	1.000
19:18683746:C:A	A15E	1.000
19:18683749:T:C	L16P	1.000
19:18683751:C:G	H17D	1.000
19:18683752:A:C	H17P	1.000
19:18683758:A:C	Q19P	1.000
19:18683762:G:C	K20N	1.000
19:18683762:G:T	K20N	1.000
19:18683764:A:C	Q21P	1.000
19:18683766:G:C	A22P	1.000
19:18683772:G:A	E24K	1.000
19:18683775:A:C	T25P	1.000

dbSNP variants (sampled 300 via entrez): RS1000072022 (19:18721318 C>T), RS1000077770 (19:18716061 A>C,G), RS1000086701 (19:18684995 C>A,G), RS1000118596 (19:18765216 C>CT), RS1000144357 (19:18732031 G>A), RS1000197855 (19:18720509 C>T), RS1000209716 (19:18776181 G>A), RS1000235025 (19:18687715 G>A), RS1000241942 (19:18697674 A>T), RS1000248569 (19:18751800 G>A,T), RS1000257329 (19:18760873 G>T), RS1000361498 (19:18681961 G>C,T), RS1000399850 (19:18750464 A>G), RS1000409219 (19:18722537 T>C), RS1000420093 (19:18721601 C>G)

Disease associations

OMIM: gene MIM:607536 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000880_25	Menarche (age at onset)	6.000000e-09
GCST002230_7	Barrett’s esophagus	6.000000e-08
GCST002231_8	Digestive system disease (Barrett’s esophagus and esophageal adenocarcinoma combined)	4.000000e-10
GCST002232_8	Esophageal adenocarcinoma	8.000000e-07
GCST002541_118	Menarche (age at onset)	9.000000e-12
GCST003435_10	Body fat percentage	2.000000e-07
GCST003435_40	Body fat percentage	8.000000e-08
GCST003435_44	Body fat percentage	5.000000e-08
GCST003435_6	Body fat percentage	1.000000e-06
GCST003740_14	Barrett’s esophagus or Esophageal adenocarcinoma	5.000000e-08
GCST004557_113	Body mass index	5.000000e-07
GCST004557_118	Body mass index	3.000000e-08
GCST004557_168	Body mass index	1.000000e-06
GCST004557_246	Body mass index	2.000000e-08
GCST004558_109	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-06
GCST004558_166	Body mass index (joint analysis main effects and physical activity interaction)	4.000000e-08
GCST004558_182	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004558_3	Body mass index (joint analysis main effects and physical activity interaction)	4.000000e-08
GCST004559_110	Body mass index in physically active individuals	2.000000e-06
GCST004559_28	Body mass index in physically active individuals	2.000000e-07
GCST007922_5	Medication use (drugs for peptic ulcer and gastro-oesophageal reflux disease)	5.000000e-08
GCST008058_24	Estimated glomerular filtration rate	5.000000e-09
GCST008059_225	Estimated glomerular filtration rate	4.000000e-07
GCST008158_79	Body mass index	1.000000e-06
GCST008832_21	Gastroesophageal reflux disease	2.000000e-09
GCST010988_18	Adult body size	5.000000e-19
GCST011122_14	Walking pace	4.000000e-09
GCST011461_3	Barrett’s esophagus or Esophageal adenocarcinoma	2.000000e-08
GCST011461_8	Barrett’s esophagus or Esophageal adenocarcinoma	1.000000e-08
GCST011462_3	Barrett’s esophagus or esophageal adenocarcinoma x sex interaction (2df test)	6.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0007800	body fat percentage
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0009923	Peptic ulcer and gastro-oesophageal reflux disease (GORD) drug use measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases methylation, decreases expression	3
sodium arsenite	increases expression, decreases expression, increases abundance	2
Arsenic	increases expression, increases methylation, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Cannabinoids	affects methylation, increases abundance	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	affects expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

13 cell lines: 13 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0455	NCI-H292	Cancer cell line	Female
CVCL_A464	NCI-H3118	Cancer cell line	Female
CVCL_B409	Hut292DM	Cancer cell line	Female
CVCL_B7H4	HCM-MEC010	Cancer cell line	Female
CVCL_D1VW	Abcam A-549 CRTC1 KO	Cancer cell line	Male
CVCL_D2AD	Abcam HCT 116 CRTC1 KO	Cancer cell line	Male
CVCL_D7FF	NCI-H292-Luc	Cancer cell line	Female
CVCL_E0ZT	Ubigene NCI-H292 EPCAM KO	Cancer cell line	Female
CVCL_LB40	PathHunter U2OS TORC1 Nuclear Translocation	Cancer cell line	Female
CVCL_Y471	UM-HMC-3A	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.