RGD Reference Report - Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. - Rat Genome Database

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Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis.

Authors: Kaplan, JM  Kim, SH  North, KN  Rennke, H  Correia, LA  Tong, HQ  Mathis, BJ  Rodriguez-Perez, JC  Allen, PG  Beggs, AH  Pollak, MR 
Citation: Kaplan JM, etal., Nat Genet. 2000 Mar;24(3):251-6.
RGD ID: 1598731
Pubmed: PMID:10700177   (View Abstract at PubMed)
DOI: DOI:10.1038/73456   (Journal Full-text)

Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion. Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition. FSGS is characterized by increased urinary protein excretion and decreasing kidney function. Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref. 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS. In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4. Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients. Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
focal segmental glomerulosclerosis susceptibilityIAGP 1598731 RGD 
focal segmental glomerulosclerosis susceptibilityISOACTN4 (Homo sapiens)1598731; 1598731 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Moderate albuminuria  IAGP 1598731 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Actn4  (actinin alpha 4)

Genes (Mus musculus)
Actn4  (actinin alpha 4)

Genes (Homo sapiens)
ACTN4  (actinin alpha 4)


Additional Information