GeneBe

TCF12

transcription factor 12, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 15:56918623-57299281

Links

ENSG00000140262 ∙ NCBI:6938 ∙ OMIM:600480 ∙ HGNC:11623 ∙ Uniprot:Q99081 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • TCF12-related craniosynostosis (Strong), mode of inheritance: AD
  • Kallmann syndrome (Strong), mode of inheritance: AR
  • Kallmann syndrome (Strong), mode of inheritance: AD
  • TCF12-related craniosynostosis (Strong), mode of inheritance: AD
  • isolated plagiocephaly (Supportive), mode of inheritance: AD
  • isolated brachycephaly (Supportive), mode of inheritance: AD
  • hypogonadotropic hypogonadism 26 with or without anosmia (Strong), mode of inheritance: AD
  • TCF12-related craniosynostosis (Strong), mode of inheritance: AD
  • TCF12-related craniosynostosis (Definitive), mode of inheritance: AD
  • TCF12-related craniosynostosis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hypogonadotropic hypogonadism 26 with or without anosmiaADEndocrineIn Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of diseaseCraniofacial; Endocrine; Musculoskeletal; Neurologic23354436

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCF12 gene.

  • not_provided (293 variants)
  • Inborn_genetic_diseases (84 variants)
  • TCF12-related_craniosynostosis (55 variants)
  • TCF12-related_disorder (19 variants)
  • not_specified (17 variants)
  • Hypogonadotropic_hypogonadism_26_with_or_without_anosmia (12 variants)
  • HYPOGONADOTROPIC_HYPOGONADISM_26_WITH_ANOSMIA (5 variants)
  • Craniosynostosis_syndrome (3 variants)
  • Male_infertility_with_azoospermia_or_oligozoospermia_due_to_single_gene_mutation (2 variants)
  • Autism_spectrum_disorder (2 variants)
  • Global_developmental_delay (1 variants)
  • Intellectual_disability (1 variants)
  • Developmental_delay (1 variants)
  • Delayed_speech_and_language_development (1 variants)
  • Coronal_craniosynostosis (1 variants)
  • Hypogonadism_with_anosmia (1 variants)
  • Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCF12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000207037.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
20
clinvar
5
clinvar
 28
missense
5
clinvar
5
clinvar
196
clinvar
17
clinvar
1
clinvar
 224
nonsense
24
clinvar
10
clinvar
1
clinvar
 35
start loss
0
frameshift
44
clinvar
18
clinvar
6
clinvar
 68
splice donor/acceptor (+/-2bp)
3
clinvar
12
clinvar
1
clinvar
 16
Total 76 45 207 37 6

Highest pathogenic variant AF is 0.00000273619

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TCF12protein_codingprotein_codingENST00000438423 19380659
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.6760.3241257280201257480.0000795
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8903383870.8730.00001954593
Missense in Polyphen107179.870.594872061
Synonymous-1.401581371.150.000006951385
Loss of Function4.58838.80.2060.00000199474

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002720.000271
Ashkenazi Jewish0.00009940.0000992
East Asian0.0001640.000163
Finnish0.00004620.0000462
European (Non-Finnish)0.00007940.0000791
Middle Eastern0.0001640.000163
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3').;
Disease
DISEASE: Craniosynostosis 3 (CRS3) [MIM:615314]: A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. {ECO:0000269|PubMed:23354436, ECO:0000269|PubMed:25271085}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Developmental Biology;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;CDO in myogenesis;Myogenesis;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

pRec
0.190

Intolerance Scores

loftool
0.622
rvis_EVS
-0.71
rvis_percentile_EVS
14.67

Haploinsufficiency Scores

pHI
0.741
hipred
Y
hipred_score
0.749
ghis
0.643

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tcf12
Phenotype
immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype;

Gene ontology

Biological process
regulation of transcription by RNA polymerase II;immune response;muscle organ development;positive regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;regulation of hematopoietic stem cell differentiation
Cellular component
nuclear chromatin;nucleus;nucleoplasm;transcription factor complex;cytoplasm;nuclear speck;intracellular membrane-bounded organelle;RNA polymerase II transcription factor complex
Molecular function
RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;transcription factor binding;enhancer binding;cAMP response element binding;protein homodimerization activity;bHLH transcription factor binding;transcription regulatory region DNA binding;SMAD binding;protein heterodimerization activity;E-box binding;HMG box domain binding