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Mendeliome

Gene: TCF12

Green List (high evidence)

TCF12 (transcription factor 12)
EnsemblGeneIds (GRCh38): ENSG00000140262
EnsemblGeneIds (GRCh37): ENSG00000140262
OMIM: 600480, Gene2Phenotype
TCF12 is in 6 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Well established gene-disease association with craniosynostosis with 38 unrelated families reported in the original gene discovery paper alone. New association with Kallman syndrome reported in PMID 32620954, though note some individuals also had craniosynostosis so may represent a spectrum.
Created: 22 Sep 2020, 9:50 p.m. | Last Modified: 22 Sep 2020, 9:50 p.m.
Panel Version: 0.4542

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Craniosynostosis 3, MIM# 615314; Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718; Kallman syndrome

Publications

Arina Puzriakova (Genomics England)

I don't know

Note monoallelic variants in this gene are a well-established cause of craniosynostosis.
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- PMID: 32620954 (2020) - 13 unrelated kindreds (11 de novo, 1 AD and 1 AR) comprising 14 affected individuals with an anosmic form of isolated GnRH deficiency (IGD) (Kallman syndrome) due to different LoF variants in TCF12.

Clinical manifestation included anosmia and pubertal failure (with reproductive phenotypes such as micropenis, bilateral cryptorchidism, hypospadias). Two unrelated individuals within the cohort additionally exhibited craniosynostosis, and a further two pedigrees had a family history of craniosynostosis (that did not affect the index case). Multiplex cases typically presented incomplete penetrance.

Loss of tcf12 in a mutant zebrafish model perturbed GnRH neuronal patterning, with concomitant expression attenuation of tcf3a/b and stub1 (latter mutated in other syndromic forms of IGD). Furthermore, restored STUB1 expression rescued loss of tcf12 in vivo.
Created: 22 Sep 2020, 1:34 p.m. | Last Modified: 22 Sep 2020, 1:34 p.m.
Panel Version: 0.4542

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Kallmann syndrome

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Craniosynostosis 3, MIM# 615314
  • Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718
  • Kallman syndrome
OMIM
600480
Clinvar variants
Variants in TCF12
Penetrance
None
Publications
Panels with this gene

History Filter Activity

26 Jan 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TCF12 were changed from Craniosynostosis 3, MIM# 615314; Kallman syndrome to Craniosynostosis 3, MIM# 615314; Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718; Kallman syndrome

22 Sep 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: tcf12 has been classified as Green List (High Evidence).

22 Sep 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TCF12 were changed from to Craniosynostosis 3, MIM# 615314; Kallman syndrome

22 Sep 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: TCF12 were set to

22 Sep 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: TCF12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: TCF12 was added gene: TCF12 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: TCF12 was set to Unknown