Autosomal dominant sensory ataxia 1

Summary

Autosomal dominant sensory ataxia 1 (MONDO:0012166) is a disease caused by RNF170 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RNF170 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant sensory ataxia 1
Mondo ID	MONDO:0012166
OMIM	608984
DOID	DOID:0111170
UMLS	C1837015
MedGen	332346
GARD	0024850
Is cancer (heuristic)	no

Also known as: ADSA · ataxia, sensory, 1, autosomal dominant · hereditary ataxia caused by mutation in RNF170 · RNF170 hereditary ataxia · SNAX1

Data availability: 11 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › atactic disorder › hereditary ataxia › autosomal dominant sensory ataxia 1

Related subtypes (19): ataxia with fasciculations, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, myoclonus-cerebellar ataxia-deafness syndrome, cataract-ataxia-deafness syndrome, ataxia-hypogonadism-choroidal dystrophy syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, Richards-Rundle syndrome, spinocerebellar ataxia-dysmorphism syndrome, ataxia-tapetoretinal degeneration syndrome, hereditary spastic paraplegia 7, EAST syndrome, juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, hereditary episodic ataxia, spastic ataxia, tremor-ataxia-central hypomyelination syndrome, hereditary cerebellar ataxia, autosomal recessive ataxia due to PEX16 deficiency, autosomal recessive ataxia due to PEX2 deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 conflicting classifications of pathogenicity, 1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
31590	NM_030954.4(RNF170):c.595C>T (p.Arg199Cys)	RNF170	Pathogenic	criteria provided, multiple submitters, no conflicts
130158	NM_030954.4(RNF170):c.640A>G (p.Ile214Val)	RNF170	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
638435	NM_030954.4(RNF170):c.304T>C (p.Cys102Arg)	RNF170	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930981	NM_030954.4(RNF170):c.346C>T (p.Arg116Ter)	RNF170	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
932477	NM_030954.4(RNF170):c.566T>G (p.Phe189Cys)	RNF170	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027753	NM_001160224.2(RNF170):c.520C>T (p.His174Tyr)	RNF170	Uncertain significance	criteria provided, single submitter
208491	NC_000008.11:g.42850904C>T	RNF170	Uncertain significance	no assertion criteria provided
2285997	NM_001160224.2(RNF170):c.419G>A (p.Arg140His)	RNF170	Uncertain significance	criteria provided, multiple submitters, no conflicts
2671743	NM_030954.4(RNF170):c.493G>C (p.Gly165Arg)	RNF170	Uncertain significance	criteria provided, single submitter
4292591	NM_030954.4(RNF170):c.535A>G (p.Thr179Ala)	RNF170	Uncertain significance	criteria provided, single submitter
522306	NM_030954.4(RNF170):c.374G>A (p.Ser125Asn)	RNF170	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RNF170	Strong	Autosomal dominant	autosomal dominant sensory ataxia 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF170	Orphanet:631082	Autosomal recessive spastic paraplegia type 85

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF170	HGNC:25358	ENSG00000120925	Q96K19	E3 ubiquitin-protein ligase RNF170	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF170	E3 ubiquitin-protein ligase RNF170	E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF170	Transcription factor	no		Znf_RING, DUF1232, Znf_RING/FYVE/PHD

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
lateral nuclear group of thalamus	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF170	281	ubiquitous	marker	lateral nuclear group of thalamus, tendon of biceps brachii, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNF170	1,165

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RNF170	Q96K19	77.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of toll-like receptor 3 signaling pathway	1	4213.0×	0.002	RNF170
response to temperature stimulus	1	1532.0×	0.003	RNF170
toll-like receptor 3 signaling pathway	1	1123.5×	0.003	RNF170
adult walking behavior	1	495.6×	0.005	RNF170
response to activity	1	324.1×	0.006	RNF170
protein K48-linked ubiquitination	1	168.5×	0.009	RNF170
gene expression	1	79.9×	0.016	RNF170
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.022	RNF170
innate immune response	1	33.6×	0.030	RNF170

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RNF170	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RNF170

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RNF170	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.