RING FINGER PROTEIN 207; RNF207

Alternative titles; symbols

• CHROMOSOME 1 OPEN READING FRAME 188; C1ORF188

HGNC Approved Gene Symbol: RNF207

Cytogenetic location: 1p36.31 Genomic coordinates (GRCh38): 1:6,206,003-6,221,298 (from NCBI)

▼ Description
RNF207 appears to play a role in cardiac repolarization by stabilizing membrane expression of the potassium channel HERG (KCNH2; 152427) (Roder et al., 2014).

▼ Cloning and Expression
Roder et al. (2014) cloned RNF207 from human heart RNA. The deduced 634-amino acid protein has an N-terminal RING domain, followed by a B-box, a B-box C-terminal domain, a C-terminal homologous region, and a C-terminal nonhomologous region. Orthologs of RNF207 were detected in all vertebrates examined except jawless and cartilaginous fish.

▼ Mapping
Hartz (2016) mapped the RNF207 gene to chromosome 1p36.31 based on an alignment of the RNF207 sequence (GenBank AK128246) with the genomic sequence (GRCh38).

▼ Gene Function
Roder et al. (2014) found that overexpression of human RNF207 shortened action potential duration in neonatal rabbit ventricular cardiomyocytes. In human U2OS or HEK293 cell lines or rat cardiomyoblast H9c2 cells, overexpression of RNF207 increased membrane expression of cotransfected HERG. Elevated HERG membrane expression increased HERG tail current density, but it had no effect on other channel parameters. Mutation analysis revealed that HERG stability depended upon the RING finger domain of RNF207. RNF207 interacted with the core-glycosylated form of HERG, but not with the fully glycosylated form, in perinuclear regions, suggesting that they interact in the endoplasmic reticulum or cis-Golgi. The C terminus of RNF207 also interacted with the chaperone HSP70 (see 140550), and cotransfection of RNF207 with HSP70 had an additive effect on HERG stability. Expression of C-terminally truncated RNF207 had a dominant-negative effect on HERG stability. A SNP in the RNF207 gene, rs846111, which results in a conservative change of gly603 to ala (G603A) in the C-terminal nonhomologous region, had no effect on RNF207 expression or function when expressed in rabbit cardiomyocytes.

▼ Animal Model
Roder et al. (2014) reported that zebrafish have 2 orthologs of RNF207: Rnf207a, which encodes a 199-amino acid protein that shares similarity with the C-terminal homologous region of RNF207, and rnf207b, which encodes a 634-amino acid protein that is highly homologous to human, rabbit, and mouse RNF207. Morpholino-mediated knockdown of rnf207b resulted in abnormal contractility and looping in developing heart. Depletion of rnf207b prolonged the duration of cardiac action potentials, which, when pronounced, resulted in 2:1 atrioventricular block.