Cataracts

Gene: SIPA1L3

Amber List (moderate evidence)

SIPA1L3 (signal induced proliferation associated 1 like 3)
EnsemblGeneIds (GRCh38): ENSG00000105738
EnsemblGeneIds (GRCh37): ENSG00000105738
OMIM: 616655, Gene2Phenotype
SIPA1L3 is in 1 panel

1 review

Ellen McDonagh (Genomics England Curator)

PMID: 25804400 - two sisters with dense white cataracts reported to be homozygous for a nonsense variant in this gene. This was heterozygous in the unaffected parents. PMID: 26231217 - One patient who had lens and ocular anterior segment abnormalities reported with a de novo balanced translocation 46,XY,t(2;19)(q37.3;q13.1). The breakpoint transected SIPA1L3 at 19q13.1, and they report reduced SIPA1L3 expression in patient lymphoblasts. A second patient with cataracts was heterozygous for a missense variant in SIPA1L3, c.442G>T, p.Asp148Tyr. In vitro studies of the variant in an epithelial cell line showed abnormal clustering of actin stress fibres and decreased formation of adherens junctions. Parental DNA samples were unavailable for study to confirm segregation. PMID: 27993984 In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. PMID: 28951961 - further evidence provided by a study reporting a spontaneous mutation was identified in a mouse line that influenced lens formation and resulted in juvenile cataracts in mice homozygous for the recessive allele. Haplotype analysis revealed a 197.5 kb segment unique to cataract-affected mice that included a single known transcript consisting of the first 14 exons of Sipa1l3, predicted to cause a truncated protein. Affected mice were homozygous for the deletion and normal mice were either heterozygous or homozygous for the wild-type allele.
Created: 30 Oct 2017, 2:29 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
?Cataract 45

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • ?Cataract 45
Tags
watchlist
OMIM
616655
Clinvar variants
Variants in SIPA1L3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

30 Oct 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

30 Oct 2017, Gel status: 0

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for SIPA1L3 were set to 25804400; 26231217; 27993984;28951961

8 Aug 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

SIPA1L3 was created by ellenmcdonagh

8 Aug 2017, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

SIPA1L3 was added to Cataractspanel. Sources: Literature