The KCNE gene family, including KCNE1, KCNE2
, KCNE3, KCNE4, and KCNE5 genes, encodes protein Mink and Mink-related peptide (MIRP1-4) protein molecules that form [beta]-subunit to constitute the functional potassium channel .
Disruption of the potassium channel regulatory subunit KCNE2
causes iron-deficient anemia.
The closest downstream gene to the risk locus is the potassium channel subunit encoding KCNE2
. Mutations in this protein are known to cause long-QT syndrome , which is associated with arrhythmias and sudden cardiac death.
Other DE genes, such as COL1A2 , OLFM4 , THBS2 , CEACAM6 , CTSE , AKR1B10 , and KCNE2
, also have been reported to be differentially expressed in GC patients comparing to controls.
The Mink expression level was influenced by the Mink S38G gene polymorphism and by other gene polymorphisms, such as KCNQ1 S140G, KCNE2
R27C, and KCNE3 R53H mutations.
None of the other variants tested showed associations with CHD below the significance threshold (P = 0.05), although the authors noted that 2 of the loci examined [MRAS (muscle RAS oncogene homolog) and KCNE2
(potassium voltage-gated channel, Isk-related family, member 2)] had summary effect sizes in the direction opposite to that described in previous reports.
(6) Furthermore, LQT4 to LQT8 are rarer forms, the involved genes being ANK2, KCNE1, KCNE2
, KCNJ2 and CACNA1C respectively.
KVLQT1, HERG, SCN5A, KCNE1, and KCNE2
. Circulation 2000; 102:1178-1185.
At the functional level, it has been found that the expression levels of some of the genes localized in the critical region (DSCR4, DSCR6; KIR4.2, GIRK2, KCNE1 and KCNE2
) are not over-expressed in the trisomic fetal brain, indicating that the DS phenotype cannot be simply explained by the effect of gene dosage imbalance.
Long QT and Jervelle Lange-Nielsen syndromes: Genetic defects and channel abnormalities Syndrome Gene Function Autosomal dominant LQT1 KCNQ1 [I.sub.ks] Decreased LQT2 KCNH2 [I.sub.Kr] Decreased LQT3 SCN5A [I.sub.Na] Decreased LQT4 ANK2 [I.sub.Na, K] Decreased LQT5 KCNE1 [I.sub.ks] Decreased LQT6 KCNE2
[I.sub.kr] Decreased LQT7 KCNJ2 [I.sub.k1] Decreased LQT8 CACNA1C [I.sub.Ca,L] Increased LQT9 CAV3 [I.sub.Na] Increased LQT10 SCN4B [I.sub.Na] Increased Autosomal recessive JLN1 KCNQ1 [I.sub.ks] Decreased JLN2 KCNE1 [I.sub.ks] Decreased Cardiac sodium ([I.sub.Na]), Potassium ([I.sub.ks], [I.sub.Kr], [I.sub.k1]) and Calcium currents
Writing about their findings in a paper, the researchers say that their work suggests that mutations of either of two gene products-proteins called KCNE2
and KCNQ1, which are already known to be involved in human cardiac arrhythmias-can also cause thyroid dysfunction.
Since then, "gain-of-function" mutations in other genes encoding potassium ion channels have been found to be associated with FAF, including KCNE2
, KCNE3 , KCNA5 , and KCNJ2 .