protein
Transcriptional repressor CTCF
Gene
CTCF
Organism
Homo sapiens(9606)
Length
727 aa
Mass
82,785 Da
CTCF (Transcriptional repressor CTCF) is a chromatin-binding factor that regulates three-dimensional chromatin architecture through sequence-specific DNA binding. It forms chromatin loops, anchors DNA to nuclear structures, and establishes boundaries between active and heterochromatic regions by binding chromatin insulators (UniProt: P49711). The protein plays diverse roles in gene regulation, including transcriptional repression of MYC and BAG1, activation of APP, and control of imprinted loci such as IGF2/H19, while also participating in X-chromosome inactivation and sister chromatid cohesion.
CTCF is widely expressed and functions across multiple genomic pathways, including regulation of the APOA1/C3/A4/A5 cluster and MHC class II genes. Mutations in CTCF are associated with intellectual developmental disorder, autosomal dominant 21 (MRD21), characterized by below-average intellectual functioning, impaired adaptive behavior, short stature, microcephaly, and developmental delay (UniProt: P49711).
CTCF is classified as a SFARI Category 2 gene with syndromic autism association (SFARI Cat 2), indicating evidence linking CTCF mutations to autism spectrum disorder, often in the context of broader neurodevelopmental phenotypes consistent with its role in chromatin-level gene regulation during brain development.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Chromatin binding factor that binds to DNA sequence specific sites and regulates the 3D structure of chromatin (PubMed:16949368, PubMed:18347100, PubMed:18654629, PubMed:19322193). Binds together strands of DNA, thus forming chromatin loops, and anchors DNA to cellular structures, such as the nuclear lamina (PubMed:18347100, PubMed:18654629, PubMed:19322193). Defines the boundaries between active and heterochromatic DNA via binding to chromatin insulators, thereby preventing interaction between promoter and nearby enhancers and silencers (PubMed:18347100, PubMed:18654629, PubMed:19322193). Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus (PubMed:16107875, PubMed:16815976, PubMed:17827499). 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 (By similarity). Mediates interchromosomal association between IGF2/H19 and WSB1/NF1 and may direct distant DNA segments to a common transcription factory (By similarity). Regulates asynchronous replication of IGF2/H19 (By similarity). Plays a critical role in gene silencing over considerable distances in the genome (By similarity). Preferentially interacts with unmethylated DNA, preventing spreading of CpG methylation and maintaining methylation-free zones (PubMed:18413740). Inversely, binding to target sites is prevented by CpG methylation (PubMed:18413740). Plays an important role in chromatin remodeling (PubMed:18413740). Can dimerize when it is bound to different DNA sequences, mediating long-range chromatin looping (PubMed:12191639). Causes local loss of histone acetylation and gain of histone methylation in the beta-globin locus, without affecting transcription (PubMed:12191639). When bound to chromatin, it provides an anchor point for nucleosomes positioning (PubMed:12191639). Seems to be essential for homologous X-chromosome pairing (By similarity). May participate with Tsix in establishing a regulatable epigenetic switch for X chromosome inactivation (PubMed:11743158). May play a role in preventing the propagation of stable methylation at the escape genes from X-inactivation (PubMed:11743158). Involved in sister chromatid cohesion (PubMed:12191639). Associates with both centromeres and chromosomal arms during metaphase and required for cohesin localization to CTCF sites (PubMed:18550811). Plays a role in the recruitment of CENPE to the pericentromeric/centromeric regions of the chromosome during mitosis (PubMed:26321640). Acts as a transcriptional repressor binding to promoters of vertebrate MYC gene and BAG1 gene (PubMed:18413740, PubMed:8649389, PubMed:9591631). Also binds to the PLK and PIM1 promoters (PubMed:12191639). Acts as a transcriptional activator of APP (PubMed:9407128). Regulates APOA1/C3/A4/A5 gene cluster and controls MHC class II gene expression (PubMed:18347100, PubMed:19322193). Plays an essential role in oocyte and preimplantation embryo development by activating or repressing transcription (By similarity). Seems to act as tumor suppressor (PubMed:12191639)
Disease associations
Intellectual developmental disorder, autosomal dominant 21MRD21
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.
Sources
Last updated 5/6/2026, 5:24:12 AM