CTCF

CCCTC-binding factor, the group of Zinc fingers C2H2-type|Cilia and flagella associated

Basic information

Region (hg38): 16:67562466-67639177

Links

ENSG00000102974 ∙ NCBI:10664 ∙ OMIM:604167 ∙ HGNC:13723 ∙ Uniprot:P49711 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome (Definitive), mode of inheritance: AD
• intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome (Supportive), mode of inheritance: AD
• intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome (Strong), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 21	AD	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	Neurologic	23746550

ClinVar

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

• not provided (133 variants)
• Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome (67 variants)
• Inborn genetic diseases (55 variants)
• not specified (19 variants)
• CTCF-related condition (6 variants)
• CTCF-Related Disorder (2 variants)
• Intellectual disability (2 variants)
• Acute megakaryoblastic leukemia in down syndrome (2 variants)
• CTCF-related syndromic intellectual disability (2 variants)
• See cases (2 variants)
• Desmoplastic/nodular medulloblastoma (1 variants)
• CTCF-Related Neurodevelopmental Disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTCF 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			1	31	3	35
missense	8	19	86	5		118
nonsense	5	2				7
start loss		1				1
frameshift	17	7				24
inframe indel			3			3
splice donor/acceptor (+/-2bp)		4				4
splice region				2	1	3
non coding		1	1	15	17	34
Total	30	34	91	51	20

Highest pathogenic variant AF is 0.0000131

Variants in CTCF

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

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

Position	Type	Phenotype	Significance	ClinVar
16-67565853-G-T			Likely benign (Nov 01, 2022)
16-67610546-G-A			Benign (Jul 03, 2018)
16-67610660-GGTT-G			Benign (Jul 27, 2020)
16-67610813-C-T			Benign (Dec 28, 2020)
16-67610830-GAAAT-TC		Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome	Likely pathogenic (Jan 19, 2018)
16-67610850-C-T			Benign (Jun 18, 2021)
16-67610861-T-C		CTCF-related disorder	Uncertain significance (Feb 08, 2023)
16-67610869-T-G		not specified	Uncertain significance (May 04, 2022)
16-67610897-G-A		Inborn genetic diseases	Uncertain significance (Nov 21, 2019)
16-67610907-C-A		Inborn genetic diseases	Pathogenic (Jul 19, 2017)
16-67610916-C-T		Inborn genetic diseases	Likely benign (Dec 01, 2023)
16-67610936-A-G			Uncertain significance (Mar 15, 2022)
16-67610950-T-G		Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome	Uncertain significance (Jan 25, 2022)
16-67610952-A-T		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
16-67610953-C-G		not specified	Likely benign (Nov 27, 2017)
16-67610953-C-T		Inborn genetic diseases	Uncertain significance (Sep 29, 2018)
16-67610960-A-G		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
16-67610962-C-A		Inborn genetic diseases	Uncertain significance (May 04, 2018)
16-67610963-A-G			Likely benign (Jul 01, 2022)
16-67610968-G-A		Intellectual disability	Likely benign (Jan 01, 2019)
16-67610972-G-A			Uncertain significance (Jul 01, 2021)
16-67610978-A-AG		Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome	Pathogenic (Dec 21, 2019)
16-67610980-G-A			Uncertain significance (Aug 01, 2022)
16-67610982-G-A			Likely benign (Oct 01, 2021)
16-67610985-C-T			Likely benign (May 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTCF	protein_coding	protein_coding	ENST00000264010	10	76777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000587	125615	0	2	125617	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.44	174	434	0.401	0.0000255	4861
Missense in Polyphen		24	144.2	0.16643		1579
Synonymous	-1.36	171	150	1.14	0.00000900	1312
Loss of Function	5.08	1	32.0	0.0312	0.00000170	404

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000897	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chromatin binding factor that binds to DNA sequence specific sites. Involved in transcriptional regulation by binding to chromatin insulators and preventing interaction between promoter and nearby enhancers and silencers. Acts as transcriptional repressor binding to promoters of vertebrate MYC gene and BAG1 gene. Also binds to the PLK and PIM1 promoters. Acts as a transcriptional activator of APP. Regulates APOA1/C3/A4/A5 gene cluster and controls MHC class II gene expression. Plays an essential role in oocyte and preimplantation embryo development by activating or repressing transcription. Seems to act as tumor suppressor. Plays a critical role in the epigenetic regulation. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, binding within the H19 imprinting control region (ICR) mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to IGF2. Plays a critical role in gene silencing over considerable distances in the genome. Preferentially interacts with unmethylated DNA, preventing spreading of CpG methylation and maintaining methylation-free zones. Inversely, binding to target sites is prevented by CpG methylation. Plays a important role in chromatin remodeling. Can dimerize when it is bound to different DNA sequences, mediating long-range chromatin looping. Mediates interchromosomal association between IGF2/H19 and WSB1/NF1 and may direct distant DNA segments to a common transcription factory. Causes local loss of histone acetylation and gain of histone methylation in the beta-globin locus, without affecting transcription. When bound to chromatin, it provides an anchor point for nucleosomes positioning. Seems to be essential for homologous X-chromosome pairing. May participate with Tsix in establishing a regulatable epigenetic switch for X chromosome inactivation. May play a role in preventing the propagation of stable methylation at the escape genes from X- inactivation. Involved in sister chromatid cohesion. Associates with both centromeres and chromosomal arms during metaphase and required for cohesin localization to CTCF sites. Regulates asynchronous replication of IGF2/H19. Plays a role in the recruitment of CENPE to the pericentromeric/centromeric regions of the chromosome during mitosis (PubMed:26321640). {ECO:0000269|PubMed:11743158, ECO:0000269|PubMed:16815976, ECO:0000269|PubMed:17827499, ECO:0000269|PubMed:18347100, ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18550811, ECO:0000269|PubMed:18654629, ECO:0000269|PubMed:19322193, ECO:0000269|PubMed:26321640, ECO:0000269|PubMed:8649389, ECO:0000269|PubMed:9591631}.
• Disease: DISEASE: Mental retardation, autosomal dominant 21 (MRD21) [MIM:615502]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Additional MRD21 features include short stature, microcephaly, and developmental delay. {ECO:0000269|PubMed:23746550}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: MECP2 and Associated Rett Syndrome;Prion disease pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;ctcf: first multivalent nuclear factor;TGF_beta_Receptor (Consensus)

Recessive Scores

• pRec: 0.251

Intolerance Scores

• loftool: 0.0330
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.784
• hipred: Y
• hipred_score: 0.783
• ghis: 0.526

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ctcf
• Phenotype: cellular phenotype; endocrine/exocrine gland 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); hematopoietic system phenotype; immune system phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: ctcf
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved dorsal

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;DNA methylation;regulation of gene expression by genetic imprinting;chromosome segregation;negative regulation of cell population proliferation;maintenance of DNA methylation;positive regulation of gene expression;nucleosome positioning;regulation of histone methylation;regulation of histone acetylation;regulation of gene expression, epigenetic;regulation of molecular function, epigenetic;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of centromeric sister chromatid cohesion;protein localization to chromosome, centromeric region
• Cellular component: chromosome, centromeric region;condensed chromosome;nucleus;nucleoplasm;nucleolus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;zinc ion binding;chromatin insulator sequence binding;sequence-specific DNA binding;transcription regulatory region DNA binding