Glaucoma congenital
Gene: THBS1EnsemblGeneIds (GRCh38): ENSG00000137801
EnsemblGeneIds (GRCh37): ENSG00000137801
OMIM: 188060, Gene2Phenotype
THBS1 is in 4 panels
1 review
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)
Missense alleles altering p.Arg1034, a highly evolutionarily conserved amino acid, in 3 unrelated and ethnically diverse families affected by congenital glaucoma.
Thbs1R1034C-mutant mice had elevated intraocular pressure (IOP), reduced ocular fluid outflow, and retinal ganglion cell loss. Histology revealed an abundant, abnormal extracellular accumulation of THBS1 with abnormal morphology of juxtacanalicular trabecular meshwork (TM), an ocular tissue critical for aqueous fluid outflow. Functional characterization showed that the THBS1 missense alleles found in affected individuals destabilized the THBS1 C-terminus, causing protein misfolding and extracellular aggregation. Analysis using a range of amino acid substitutions at position R1034 showed that the extent of aggregation was correlated with the change in protein-folding free energy caused by variations in amino acid structure.
Sources: LiteratureCreated: 2 Feb 2023, 3:17 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Congenital glaucoma MONDO:0020366, THBS1-related
Publications
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Green
- Literature
- Phenotypes
-
- Congenital glaucoma MONDO:0020366, THBS1-related
- OMIM
- 188060
- Clinvar variants
- Variants in THBS1
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: thbs1 has been classified as Green List (High Evidence).
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: thbs1 has been classified as Green List (High Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)gene: THBS1 was added gene: THBS1 was added to Glaucoma congenital. Sources: Literature Mode of inheritance for gene: THBS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: THBS1 were set to 36453543 Phenotypes for gene: THBS1 were set to Congenital glaucoma MONDO:0020366, THBS1-related Review for gene: THBS1 was set to GREEN