RNF170

Chr 8

ring finger protein 170

Also known as: ADSA, SNAX1, SPG85

NCBI Gene: 81790ENSG00000120925UniProt: Q96K19

This gene encodes a RING domain-containing protein that resides in the endoplasmic reticulum (ER) membrane. This protein functions as an E3 ubiquitin ligase and mediates ubiquitination and processing of inositol 1,4,5-trisphosphate (IP3) receptors via the ER-associated protein degradation pathway. It is recruited to the activated IP3 receptors by the ERLIN1/ERLIN2 complex to which it is constitutively bound. Mutations in this gene are associated with autosomal dominant sensory ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

Primary Disease Associations & Inheritance

UniProtAtaxia, sensory, 1, autosomal dominant
UniProtSpastic paraplegia 85, autosomal recessive
118
ClinVar variants
55
Pathogenic / LP
0.51
pLI score
0
Active trials
Clinical Summary— RNF170
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 48 VUS of 118 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.52LOEUF
pLI 0.511
Z-score 2.86
OE 0.20 (0.09–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.42Z-score
OE missense 0.66 (0.56–0.79)
93 obs / 140.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.09–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.56–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 3 / 14.9Missense obs/exp: 93 / 140.3Syn Z: 0.81

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic4
VUS48
Likely Benign6
Benign5
Conflicting4
51
Pathogenic
4
Likely Pathogenic
48
VUS
6
Likely Benign
5
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
49
0
51
Likely Pathogenic
0
1
3
0
4
VUS
0
33
14
1
48
Likely Benign
0
3
1
2
6
Benign
0
1
3
1
5
Conflicting
—4
Total139704118

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.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A novel homozygous variant in RNF170 causes hereditary spastic paraplegia: a case report and review of the literature.
Chouery E et al.·Neurogenetics
2022Review
RNF170 mutation causes autosomal dominant sensory ataxia with variable pyramidal involvement.
Van Daele SH et al.·Eur J Neurol
2022
Canine RNF170 Single Base Deletion in a Naturally Occurring Model for Human Neuroaxonal Dystrophy.
Cook SR et al.·Mov Disord
2024Functional
Whole exome sequencing in Serbian patients with hereditary spastic paraplegia.
Brankovic M et al.·Neurogenetics
2024Cohort
RNF170-Related Hereditary Spastic Paraplegia: Confirmation by a Novel Mutation.
de Sainte Agathe JM et al.·Mov Disord
2021
ITPR1 Deletion in a Patient With Sensory Ataxic Neuropathy and Sjögren Syndrome.
Haddad S et al.·J Peripher Nerv Syst
2025Case report
A mutation in the RNF170 gene causes autosomal dominant sensory ataxia.
Valdmanis PN et al.·Brain
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools