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References OMIM Gene GeneReviews HGMD HGNC
last update : 15-03-2016
Symbol PHA2E
Location 2q36.2
Name pseudohypoaldosteronism, type IIE
Other name(s) Familial hyperkalemic hypertension
Corresponding gene CUL3
Other symbol(s) FHHT
Main clinical features
  • renal hyperkalemia and otherwise normal renal function but with hypertension and acidosis
  • reversed by thiazide diuretics, which inhibit the Na–Cl cotransporter in the distal nephron of the kidney
  • Genetic determination autosomal dominant
    Function/system disorder kidney and urinary tract
    Type disease
  • mutations in Cullin3 (CUL3) causing deletion of 57 amino acids encoded by exon 9 (CUL3delta9) cause hypertension (PMID: 26100637))
  • CUL3delta9-associated ubiquitin ligase activity toward RHOA is impaired, suggesting that Cul3delta9 mutations may act dominantly by sequestering substrate adaptors and disrupting CUL3WT complexes (PMID: 26100637))
  • mutations abrogate degradation of WNK kinases, which regulate the renal NaCl cotransporter (NCC) (PMID: 25311533))