Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
Disease
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Query: EC:3.4.21.69 (
APC
)
16,337
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
This review reports the main molecular alterations leading to development of benign cortisol- and/or aldosterone-secreting adrenal tumors. Causes of adrenal Cushing syndrome can be divided in 2 groups: multiple bilateral tumors or adenomas secreting cortisol. Bilateral causes are mainly primary pigmented nodular adrenocortical disease, most of the time due to
PRKAR1A
germline-inactivating mutations, and primary bilateral macronodular adrenal hyperplasia that can be caused in some rare syndromic cases by germline-inactivating mutations of
MEN1
,
APC
, and
FH
and of
ARMC5
in isolated forms.
PRKACA
somatic-activating mutations are the main alterations in unilateral cortisol-producing adenomas. In primary hyperaldosteronism (PA), familial forms were identified in 1% to 5% of cases: familial hyperaldosteronism type I (FH-I) due to a chimeric
CYP11B1/CYP11B2
hybrid gene, FH-II due to
CLCN-2
germline mutations, FH-III due to
KCNJ5
germline mutations, FH-IV due to
CACNA1H
germline mutations and PA, and seizures and neurological abnormalities syndrome due to
CACNA1D
germline mutations. Several somatic mutations have been found in aldosterone-producing adenomas in
KCNJ5
,
ATP1A1
,
ATP2B3
,
CACNA1D
, and
CTNNB1
genes. In addition to these genetic alterations, genome-wide approaches identified several new alterations in transcriptome, methylome, and miRnome studies, highlighting new pathways involved in steroid dysregulation.
...
PMID:Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome. 3278 15
