RNF170

Chr 8ADAR

ring finger protein 170

Also known as: ADSA, SNAX1, SPG85

The protein is an E3 ubiquitin ligase located in the endoplasmic reticulum membrane that mediates ubiquitination and degradation of inositol 1,4,5-trisphosphate receptors via the ER-associated protein degradation pathway. Mutations cause autosomal dominant sensory ataxia and autosomal recessive spastic paraplegia, affecting the nervous system with sensory and motor dysfunction. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.52), and exhibits both dominant and recessive inheritance patterns depending on the specific condition.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismAD/ARLOEUF 0.522 OMIM phenotypes
Clinical SummaryRNF170
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 49 VUS of 126 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.511
Z-score 2.86
OE 0.20 (0.090.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.42Z-score
OE missense 0.66 (0.560.79)
93 obs / 140.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.090.52)
00.351.4
Missense OE0.66 (0.560.79)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 3 / 14.9Missense obs/exp: 93 / 140.3Syn Z: 0.81
DN
0.6162th %ile
GOF
0.6149th %ile
LOF
0.3067th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOF1 literature citation

Literature Evidence

GOFCoinjection of the mutant and wildtype mRNAs resulted in an intermediate number of disturbed embryos, suggesting a toxic gain of function.PMID:17190954

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

ClinVar Variant Classifications

126 submitted variants in ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic4
VUS49
Likely Benign6
Benign5
Conflicting4
51
Pathogenic
4
Likely Pathogenic
49
VUS
6
Likely Benign
5
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
47
0
51
Likely Pathogenic
0
1
3
0
4
VUS
0
34
14
1
49
Likely Benign
0
3
1
2
6
Benign
0
1
3
1
5
Conflicting
4
Total340684119

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF170 · 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.

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Clinical Literature
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