Human Gene Module / Chromosome 15 / TCF12

TCF12transcription factor 12

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
7 / 9
Rare Variants / Common Variants
28 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
15q21.3
Associated Disorders
-
Relevance to Autism

Trio-based whole-exome sequencing of 168 patients with low-functioning ASD at Sun Yat-sen Memorial Hospital in Wu et al., 2025 identified a de novo loss-of-function variant in the TCF12 gene in a patient clinically diagnosed with ASD based on DSM-5 criteria and presenting with global developmental delay/intellectual disability. Additional de novo loss-of-function variants, as well as a de novo missense variant prediced to be deleterious by CADD, REVEL, and MPC, were previously reported in TCF12 in ASD probands from the MSSNG cohort, the SPARK cohort, and the Autism Sequencing Consortium (Yuen et al., 2016; Zhou et al., 2022; Fu et al., 2022; Trost et al., 2022). TCF12 was identified in Wang et al., 2020 as an novel NDD risk gene, with ultra-rare likely gene-disruptive variants reaching FDR significance following a combined analysis of new ASD and NDD cases with published data. Autism spectrum disorder was been reported in a subset of individuals with craniosynostosis 3 (Sharma et al., 2013; Paumard-Hernndez et al., 2015).

Molecular Function

The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Heterozygous mutations in this gene are responsible for craniosynostosis 3 (OMIM 615314).

External Links
Gene CardPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
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Reports related to TCF12 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Vikram P Sharma et al. (2013) No ASD
2 Support - Beatriz Paumard-Hernández et al. (2015) No ASD
3 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
4 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
5 Support - Zhou X et al. (2022) Yes -
6 Support - Fu JM et al. (2022) Yes -
7 Support - Chan AJS et al. (2022) Yes -
8 Support - Trost B et al. (2022) Yes -
9 Primary - Ruohao Wu et al. (2025) Yes -
Rare Variants   (28)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.446C>G p.Ser149Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.921C>A p.Tyr307Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.1876C>T p.Arg626Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.390+1G>A p.? splice_site_variant De novo - - 33004838 Wang T et al. (2020)
c.590C>T p.Pro197Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.616C>T p.Arg206Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.931delT p.Ser311fs frameshift_variant De novo - - 35982160 Fu JM et al. (2022)
c.1018G>C p.Gly340Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1094G>A p.Gly365Glu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1454G>A p.Arg485Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1486G>T p.Asp496Tyr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1838G>A p.Arg613His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2027A>G p.Glu676Gly missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1433C>G p.Ser478Ter stop_gained De novo - Simplex 36368308 Trost B et al. (2022)
c.1036-1G>T p.? splice_site_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.1189-2A>G p.? splice_site_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.1837C>T p.Arg613Cys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.953G>A p.Gly318Glu missense_variant Familial Paternal - 33004838 Wang T et al. (2020)
c.694del p.His232ThrfsTer13 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.1877G>A p.Arg626Gln missense_variant De novo - Multiplex 33004838 Wang T et al. (2020)
c.281delA p.His94LeufsTer10 frameshift_variant De novo - - 41127290 Ruohao Wu et al. (2025)
c.160delA Arg54GlufsTer33 frameshift_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.1099C>T p.Pro367Ser missense_variant Familial Maternal Simplex 33004838 Wang T et al. (2020)
c.1704del p.Ser569ProfsTer22 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.356del p.Leu119ArgfsTer16 frameshift_variant De novo - Multiplex 33004838 Wang T et al. (2020)
c.1808G>A p.Arg603Gln missense_variant Familial Paternal Multiplex 33004838 Wang T et al. (2020)
c.675del p.Phe226LeufsTer19 frameshift_variant Unknown Not maternal - 33004838 Wang T et al. (2020)
c.1106_1107insG p.Leu370SerfsTer21 frameshift_variant Familial Maternal Simplex 36309498 Chan AJS et al. (2022)
Common Variants  

No common variants reported.

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