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Mendeliome

Gene: TBC1D1

Green List (high evidence)

TBC1D1 (TBC1 domain family member 1)
EnsemblGeneIds (GRCh38): ENSG00000065882
EnsemblGeneIds (GRCh37): ENSG00000065882
OMIM: 609850, Gene2Phenotype
TBC1D1 is in 3 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

1 heterozygous de novo frameshift variant in TBC1D1 in 1 CAKUT.
3 further CAKUT cases with three novel or rare inherited heterozygous TBC1D1 missense variants predicted to be pathogenic. TBC1D1 mutations affected Ser237-phosphorylation or protein stability and thereby act as hypomorphs.

Supportive functional data:
Tbc1d1 showed widespread expression in the developing murine urogenital system. A mild CAKUT spectrum phenotype, including anomalies observed in patients carrying TBC1D1 mutations, was found in kidneys of some Tbc1d1 (-/-) mice. Significantly reduced Glut4 levels were detected in kidneys of Tbc1d1 (-/-) mice and the dysplastic kidney of a TBC1D1 mutation carrier versus controls. TBC1D1 and SLC2A4 encoding GLUT4 were highly expressed in human fetal kidney. These data demonstrate heterozygous deactivating TBC1D1 mutations in CAKUT patients with a similar renal and ureteral phenotype, and provide evidence that TBC1D1 mutations may contribute to CAKUT pathogenesis, possibly via a role in glucose homeostasis.
Created: 25 Mar 2022, 9:39 p.m. | Last Modified: 25 Mar 2022, 9:39 p.m.
Panel Version: 0.11943

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
CAKUT; Non-syndromic renal or urinary tract malformation, MONDO:0019720

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • CAKUT
  • Non-syndromic renal or urinary tract malformation, MONDO:0019720
OMIM
609850
Clinvar variants
Variants in TBC1D1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Mar 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: tbc1d1 has been classified as Green List (High Evidence).

25 Mar 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TBC1D1 were changed from to CAKUT; Non-syndromic renal or urinary tract malformation, MONDO:0019720

25 Mar 2022, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: TBC1D1 were set to

25 Mar 2022, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: TBC1D1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: TBC1D1 was added gene: TBC1D1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: TBC1D1 was set to Unknown