CTC1

CST telomere replication complex component 1, the group of CST complex

Basic information

Region (hg38): 17:8224814-8248058

Previous symbols: [ "C17orf68" ]

Links

ENSG00000178971 ∙ NCBI:80169 ∙ OMIM:613129 ∙ HGNC:26169 ∙ Uniprot:Q2NKJ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebroretinal microangiopathy with calcifications and cysts 1 (Definitive), mode of inheritance: AR
• cerebroretinal microangiopathy with calcifications and cysts 1 (Strong), mode of inheritance: AR
• cerebroretinal microangiopathy with calcifications and cysts 1 (Strong), mode of inheritance: AR
• dyskeratosis congenita (Supportive), mode of inheritance: AD
• Coats plus syndrome (Supportive), mode of inheritance: AR
• cerebroretinal microangiopathy with calcifications and cysts 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebroretinal microangiopathy with calcifications and cysts 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Cardiovascular; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	3402627; 8628470; 15002047; 15079028; 16943371; 18076099; 21523908; 22267198; 22387016

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTC1 gene.

• Dyskeratosis congenita (1214 variants)
• not provided (148 variants)
• Cerebroretinal microangiopathy with calcifications and cysts 1 (144 variants)
• not specified (74 variants)
• Inborn genetic diseases (70 variants)
• Dyskeratosis Congenita, Recessive (8 variants)
• CTC1-related condition (7 variants)
• Coats plus syndrome (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTC1 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			11	227	5	243
missense	2	3	529	15	5	554
nonsense	24	3	2			29
start loss	2	2				4
frameshift	31	12	4			47
inframe indel	1		7			8
splice donor/acceptor (+/-2bp)		10	1	1		12
splice region	1		33	43	1	78
non coding			121	120	42	283
Total	60	30	675	363	52

Highest pathogenic variant AF is 0.000355

Variants in CTC1

This is a list of pathogenic ClinVar variants found in the CTC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-8224925-C-G		Dyskeratosis congenita	Likely benign (Jan 12, 2018)
17-8224949-T-C		Dyskeratosis congenita	Benign (Jan 12, 2018)
17-8224982-C-A		not specified • Dyskeratosis congenita	Uncertain significance (Jan 12, 2018)
17-8224994-C-T		Dyskeratosis congenita	Uncertain significance (Jan 12, 2018)
17-8225101-G-A		Dyskeratosis congenita	Uncertain significance (Jan 12, 2018)
17-8225254-C-G		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225332-T-G		Dyskeratosis congenita	Benign (Jan 13, 2018)
17-8225338-C-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225396-C-T		Dyskeratosis congenita	Uncertain significance (Jan 12, 2018)
17-8225455-A-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225495-G-A		Dyskeratosis congenita	Uncertain significance (Jan 12, 2018)
17-8225644-G-A		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225650-C-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225682-C-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225755-A-G		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225808-AAT-A		Dyskeratosis Congenita, Recessive	Uncertain significance (Jun 14, 2016)
17-8225827-T-C		Dyskeratosis congenita	Uncertain significance (Jan 12, 2018)
17-8225842-A-G		Dyskeratosis congenita	Benign (Jan 13, 2018)
17-8225843-C-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225884-A-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8225938-C-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8226034-C-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)
17-8226065-G-C		Dyskeratosis congenita	Likely benign (Jan 12, 2018)
17-8226074-C-A		Dyskeratosis congenita	Likely benign (Jan 13, 2018)
17-8226090-C-T		Dyskeratosis congenita	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTC1	protein_coding	protein_coding	ENST00000315684	23	21172

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.60e-11	1.00	124451	0	349	124800	0.00140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.503	645	682	0.946	0.0000388	7726
Missense in Polyphen		190	222.44	0.85417		2753
Synonymous	-0.0376	284	283	1.00	0.0000157	2613
Loss of Function	3.97	29	63.0	0.461	0.00000327	673

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00181	0.00181
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.000835	0.000835
Finnish	0.00427	0.00428
European (Non-Finnish)	0.00135	0.00135
Middle Eastern	0.000835	0.000835
South Asian	0.000628	0.000621
Other	0.00231	0.00231

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Involved in telomere maintenance (PubMed:19854131, PubMed:22863775). Involved in genome stability (PubMed:22863775). May be in involved in telomeric C-strand fill- in during late S/G2 phase (By similarity). {ECO:0000250|UniProtKB:Q5SUQ9, ECO:0000269|PubMed:19854130, ECO:0000269|PubMed:19854131, ECO:0000269|PubMed:22763445, ECO:0000269|PubMed:22863775, ECO:0000269|PubMed:25483097}.
• Disease: DISEASE: Cerebroretinal microangiopathy with calcifications and cysts 1 (CRMCC1) [MIM:612199]: An autosomal recessive pleiomorphic disorder characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline. Patients also have retinal telangiectasia and exudates (Coats disease) as well as extraneurologic manifestations, including osteopenia with poor bone healing and a high risk of gastrointestinal bleeding and portal hypertension caused by vasculature ectasias in the stomach, small intestine, and liver. Some individuals also have hair, skin, and nail changes, as well as anemia and thrombocytopenia. {ECO:0000269|PubMed:22267198, ECO:0000269|PubMed:22387016}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: -0.63
• rvis_percentile_EVS: 16.81

Haploinsufficiency Scores

• pHI: 0.128
• hipred: N
• hipred_score: 0.271
• ghis: 0.533

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ctc1
• Phenotype: immune system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: telomere maintenance;cellular response to DNA damage stimulus;regulation of G2/M transition of mitotic cell cycle;telomere maintenance via telomere lengthening;telomere capping;negative regulation of telomere maintenance via telomerase;multicellular organism growth;positive regulation of DNA replication;positive regulation of fibroblast proliferation;spleen development;thymus development;bone marrow development;hematopoietic stem cell proliferation;replicative senescence
• Cellular component: nuclear chromosome, telomeric region;nucleus;CST complex
• Molecular function: single-stranded DNA binding;protein binding;telomeric DNA binding;G-rich strand telomeric DNA binding