protein
Transcription factor 4
aka TCF-4
Gene
TCF4
Organism
Homo sapiens(9606)
Length
667 aa
Mass
71,308 Da
## Summary: TCF4 (Transcription Factor 4)
TCF4 is a transcription factor that binds to E-box DNA sequences (5'-CANNTG-3') to regulate gene expression (UniProt: P15884). It plays a key role in initiating neuronal differentiation and activates transcription of target genes including somatostatin receptor 2, preferentially binding to extended E-box variants such as 5'-ACANNTGT-3' or 5'-CCANNTGG-3'.
TCF4 mutations are associated with Pitt-Hopkins syndrome, a developmental disorder characterized by intellectual disability, distinctive facial features, and breathing abnormalities including intermittent hyperventilation and apnea (UniProt: P15884). The protein is also linked to Fuchs endothelial corneal dystrophy type 3, an ocular condition affecting corneal endothelium. TCF4 is classified as a syndromic gene in neurodevelopmental disease.
TCF4 is curated as a category 2 (strong evidence) autism spectrum disorder-associated gene in syndromic contexts (SFARI Cat 2). Its role in neuronal differentiation and documented involvement in neurodevelopmental syndromes positions it as relevant to autism and related neurodevelopmental conditions, particularly in syndromic presentations.
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
Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'
Disease associations
Pitt-Hopkins syndromePTHS
A syndrome characterized by intellectual disability, wide mouth and distinctive facial features, and intermittent hyperventilation followed by apnea. Features include intellectual disability with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing anomalies, severe motor developmental delay, motor incoordination, ocular anomalies, constipation, seizures, typical behavior and subtle brain abnormalities.
Corneal dystrophy, Fuchs endothelial, 3FECD3
A late-onset form of Fuchs endothelial corneal dystrophy, a disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition.
Sources
Last updated 5/6/2026, 5:23:43 AM