RNF207

Chr 1

ring finger protein 207

Also known as: C1orf188

The protein enables Hsp70 binding and may stabilize membrane expression of the KCNH2 potassium channel involved in cardiac repolarization. Mutations cause long QT syndrome, a cardiac arrhythmia disorder that can lead to sudden death. The gene shows extremely low constraint against loss-of-function variants (pLI ~0), suggesting it tolerates such mutations well.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
56
P/LP submissions
0%
P/LP missense
0.95
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryRNF207
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 123 VUS of 219 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.000
Z-score 1.77
OE 0.67 (0.480.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.45Z-score
OE missense 0.93 (0.861.02)
353 obs / 377.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.480.95)
00.351.4
Missense OE0.93 (0.861.02)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 23 / 34.2Missense obs/exp: 353 / 377.9Syn Z: 0.90
DN
0.6453th %ile
GOF
0.7127th %ile
LOF
0.3841th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

219 submitted variants in ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic3
VUS123
Likely Benign9
Benign2
53
Pathogenic
3
Likely Pathogenic
123
VUS
9
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
1
0
2
0
3
VUS
1
119
3
0
123
Likely Benign
0
8
0
1
9
Benign
0
1
1
0
2
Total2128591190

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RNF207 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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