RNF207

Chr 1

ring finger protein 207

Also known as: C1orf188

NCBI Gene: 388591 ENSG00000158286 UniProt: Q6ZRF8 OMIM: 616923

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables Hsp70 protein binding activity and transmembrane transporter binding activity. Involved in positive regulation of gene expression. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.95

Clinical Summary— RNF207

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 121 VUS of 160 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.77

OE 0.67 (0.48–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.45Z-score

OE missense 0.93 (0.86–1.02)

353 obs / 377.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.48–0.95)

0≤0.351.4

Missense OE?0.93 (0.86–1.02)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 23 / 34.2Missense obs/exp: 353 / 377.9Syn Z: 0.90

This gene — mechanism propensity

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

160 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS121

Likely Benign9

Benign1

Likely Pathogenic

121

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	1	120	0	121
Likely Benign	0	8	1	9
Benign	0	1	0	1
Total	2	129	1	132

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

View in ClinVar →

58 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap RNF207 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →