CTCF

Chr 16

CCCTC-binding factor

Also known as: CFAP108, FAP108, MRD21

NCBI Gene: 10664ENSG00000102974UniProt: P49711

This gene is a member of the BORIS + CTCF gene family and encodes a transcriptional regulator protein with 11 highly conserved zinc finger (ZF) domains. This nuclear protein is able to use different combinations of the ZF domains to bind different DNA target sequences and proteins. Depending upon the context of the site, the protein can bind a histone acetyltransferase (HAT)-containing complex and function as a transcriptional activator or bind a histone deacetylase (HDAC)-containing complex and function as a transcriptional repressor. If the protein is bound to a transcriptional insulator element, it can block communication between enhancers and upstream promoters, thereby regulating imprinted expression. Mutations in this gene have been associated with invasive breast cancers, prostate cancers, and Wilms' tumors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal dominant 21

Clinical highlights

Gene-disease validity (ClinGen)
syndromic intellectual disability · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
408
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.15
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — CTCF
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.15LOEUF
pLI 1.000
Z-score 5.08
OE 0.03 (0.01–0.15)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
4.44Z-score
OE missense 0.40 (0.35–0.45)
174 obs / 434.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.03 (0.01–0.15)
0≤0.351.4
Missense OE?0.40 (0.35–0.45)
0≤0.61.4
Synonymous OE?1.14
0≤1.21.6
LoF obs/exp: 1 / 32.0Missense obs/exp: 174 / 434.4Syn Z: -1.36

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CTCF · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients