RNF175

Chr 4

ring finger protein 175

RNF175 encodes a ubiquitin protein ligase that functions in the endoplasmic reticulum-associated degradation (ERAD) pathway and is active in Golgi and ER membranes. The gene is not highly constrained against loss-of-function variants, but specific disease associations and inheritance patterns have not been established from the available data.

Summary from RefSeq
Research Assistant →
0
Active trials
0
Pubs (1 yr)
28
P/LP submissions
0%
P/LP missense
1.43
LOEUF
DN
Mechanism· predicted
Clinical SummaryRNF175
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 45 VUS of 80 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.43LOEUF
pLI 0.000
Z-score 0.10
OE 0.98 (0.681.43)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.16Z-score
OE missense 0.97 (0.851.10)
165 obs / 170.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.98 (0.681.43)
00.351.4
Missense OE0.97 (0.851.10)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 19 / 19.5Missense obs/exp: 165 / 170.9Syn Z: 0.02
DN
0.7133th %ile
GOF
0.6052th %ile
LOF
0.4039th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

80 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic3
VUS45
Likely Benign1
25
Pathogenic
3
Likely Pathogenic
45
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
3
0
3
VUS
0
43
2
0
45
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total04331074

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF175 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found