TCF12

Protein identityUniProt · HPA

UniProt accession

Q99081

Gene

TCF12

Ensembl

ENSG00000140262

Chromosome

15

Canonical length

682 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Nuclear speckles

OverviewNCBI Gene

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. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

682 residues, UniProt reviewed canonical sequence.

>Q99081|TCF12
     1  MNPQQQRMAA IGTDKELSDL LDFSAMFSPP VNSGKTRPTT LGSSQFSGSG IDERGGTTSW
    61  GTSGQPSPSY DSSRGFTDSP HYSDHLNDSR LGAHEGLSPT PFMNSNLMGK TSERGSFSLY
   121  SRDTGLPGCQ SSLLRQDLGL GSPAQLSSSG KPGTAYYSFS ATSSRRRPLH DSAALDPLQA
   181  KKVRKVPPGL PSSVYAPSPN SDDFNRESPS YPSPKPPTSM FASTFFMQDG THNSSDLWSS
   241  SNGMSQPGFG GILGTSTSHM SQSSSYGNLH SHDRLSYPPH SVSPTDINTS LPPMSSFHRG
   301  STSSSPYVAA SHTPPINGSD SILGTRGNAA GSSQTGDALG KALASIYSPD HTSSSFPSNP
   361  STPVGSPSPL TGTSQWPRPG GQAPSSPSYE NSLHSLQSRM EDRLDRLDDA IHVLRNHAVG
   421  PSTSLPAGHS DIHSLLGPSH NAPIGSLNSN YGGSSLVASS RSASMVGTHR EDSVSLNGNH
   481  SVLSSTVTTS STDLNHKTQE NYRGGLQSQS GTVVTTEIKT ENKEKDENLH EPPSSDDMKS
   541  DDESSQKDIK VSSRGRTSST NEDEDLNPEQ KIEREKERRM ANNARERLRV RDINEAFKEL
   601  GRMCQLHLKS EKPQTKLLIL HQAVAVILSL EQQVRERNLN PKAACLKRRE EEKVSAVSAE
   661  PPTTLPGTHP GLSETTNPMG HM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TCF12 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.66

Highest tissue expression

124 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TCF12.

Disease | AllUniProt

Conditions TCF12 is implicated in, by any mechanism.

• Craniosynostosis 3 (CRS3) MIM:615314
• Hypogonadotropic hypogonadism 26 with or without anosmia (HH26) MIM:619718

Disease | GeneticClinVar

138 pathogenic / likely-pathogenic of 560 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• TCF12-related craniosynostosis
• Hypogonadotropic hypogonadism 26 with or without anosmia
• TCF12-related disorder
• HYPOGONADOTROPIC HYPOGONADISM 26 WITH ANOSMIA
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.37

gnomAD pLI

0.68

gnomAD missense Z

0.89

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell differentiation
• gene expression
• immune response
• muscle organ development
• nervous system development
• positive regulation of gene expression
• positive regulation of neuron differentiation
• positive regulation of transcription by RNA polymerase II
• regulation of transcription by RNA polymerase II
• response to gonadotropin-releasing hormone

Molecular functions

• bHLH transcription factor binding
• cAMP response element binding
• cis-regulatory region sequence-specific DNA binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription factor binding
• E-box binding
• HMG box domain binding
• protein heterodimerization activity
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• SMAD binding

Cellular components

• chromatin
• cytoplasm
• nuclear speck
• nucleoplasm
• nucleus
• RNA polymerase II transcription regulator complex
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Myc-type, basic helix-loop-helix (bHLH) domain
• Helix-loop-helix DNA-binding domain superfamily
• Neuronal Differentiation E-box Binding Transcription Factors
• Helix-loop-helix DNA-binding domain

KeywordsUniProt

• Craniosynostosis
• Developmental protein
• Differentiation
• DNA-binding
• Hypogonadotropic hypogonadism
• Isopeptide bond
• Kallmann syndrome
• Neurogenesis
• Nucleus
• Phosphoprotein
• Transcription
• Transcription regulation
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of TCF12 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BHLHA9
• NEUROD2
• PTF1A
• RUNX1T1
• ZNF652
• ASCL4
• HEXIM2
• ID1
• ID2
• ID3
• MYF6
• NEUROG3
• TAL1
• TAL2
• TWIST2