CRTC1

CREB regulated transcription coactivator 1

Basic information

Region (hg38): 19:18683678-18782333

Previous symbols: [ "MECT1" ]

Links

ENSG00000105662 ∙ NCBI:23373 ∙ OMIM:607536 ∙ HGNC:16062 ∙ Uniprot:Q6UUV9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRTC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRTC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense			25			25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	25	4	2

Variants in CRTC1

This is a list of pathogenic ClinVar variants found in the CRTC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-18742927-C-T			Likely benign (Jun 26, 2018)
19-18744139-C-T		not specified	Uncertain significance (Aug 01, 2022)
19-18745900-G-C		not specified	Uncertain significance (Sep 25, 2023)
19-18745945-C-G		not specified	Uncertain significance (Apr 09, 2024)
19-18747056-G-A		not specified	Uncertain significance (Feb 03, 2022)
19-18747094-C-T			Likely benign (Jun 22, 2018)
19-18747096-C-T		not specified	Uncertain significance (Jan 26, 2022)
19-18749822-C-T		not specified	Uncertain significance (Jan 08, 2024)
19-18753490-A-G			Benign (Feb 08, 2018)
19-18753562-A-G		not specified	Uncertain significance (Jul 06, 2021)
19-18760017-G-A			Likely benign (Mar 29, 2018)
19-18760054-G-A		not specified	Uncertain significance (Dec 04, 2024)
19-18760124-C-T		not specified	Uncertain significance (Sep 08, 2024)
19-18760188-G-A			Benign (Mar 29, 2018)
19-18760222-G-A		not specified	Uncertain significance (Sep 16, 2021)
19-18765436-C-T		not specified	Uncertain significance (Sep 01, 2021)
19-18765466-A-G		not specified	Uncertain significance (Nov 13, 2023)
19-18765494-C-T		not specified	Uncertain significance (May 05, 2023)
19-18768599-G-A		not specified	Uncertain significance (Jun 23, 2023)
19-18768645-G-A		not specified	Uncertain significance (Sep 20, 2023)
19-18768650-C-T		not specified	Uncertain significance (Dec 19, 2022)
19-18768654-C-T		not specified	Uncertain significance (Sep 27, 2021)
19-18768744-C-A		not specified	Uncertain significance (Jul 25, 2023)
19-18768750-C-A		not specified	Uncertain significance (Sep 14, 2023)
19-18768750-C-T		not specified	Uncertain significance (Jun 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRTC1	protein_coding	protein_coding	ENST00000338797	15	98518

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.531	0.469	125663	0	25	125688	0.0000995

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.33	274	406	0.675	0.0000260	4150
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000537	0.000536
Ashkenazi Jewish	0.000199	0.000199
East Asian	0.000112	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.000112	0.000109
South Asian	0.0000658	0.0000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• 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.
• Pathway: HTLV-I infection - Homo sapiens (human);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Mesodermal Commitment Pathway;AP-1 transcription factor network (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.193
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.85

Haploinsufficiency Scores

• pHI: 0.238
• hipred: Y
• hipred_score: 0.673
• ghis: 0.643

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.917

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Crtc1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; reproductive system phenotype; hematopoietic system phenotype

Gene ontology

• 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;rhythmic process;protein homotetramerization;energy homeostasis;postsynapse to nucleus signaling pathway;positive regulation of dendrite development;positive regulation of long-term synaptic potentiation;negative regulation of membrane hyperpolarization
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane;postsynaptic density;nuclear body;dendrite;neuronal cell body;glutamatergic synapse
• Molecular function: protein binding;cAMP response element binding protein binding