Spinocerebellar ataxia, autosomal recessive 31

Summary

Spinocerebellar ataxia, autosomal recessive 31 (MONDO:0030323) is a disease caused by ATG7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATG7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia, autosomal recessive 31
Mondo ID	MONDO:0030323
OMIM	619422
DOID	DOID:0070412
UMLS	C5543627
MedGen	1786855
GARD	0025538
Is cancer (heuristic)	no

Also known as: SCAR31 · spinocerebellar ataxia, autosomal recessive 31

Data availability: 17 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive cerebellar ataxia › spinocerebellar ataxia, autosomal recessive 31

Related subtypes (28): Charlevoix-Saguenay spastic ataxia, infantile-onset autosomal recessive nonprogressive cerebellar ataxia, autosomal recessive spinocerebellar ataxia 7, autosomal recessive ataxia, Beauce type, RIDDLE syndrome, autosomal recessive ataxia due to ubiquinone deficiency, autosomal recessive spinocerebellar ataxia 10, ataxia with oculomotor apraxia type 3, autosomal recessive spinocerebellar ataxia 14, autosomal recessive spinocerebellar ataxia 16, Lichtenstein-Knorr syndrome, autosomal recessive spinocerebellar ataxia 20, spinocerebellar ataxia, autosomal recessive 22, spinocerebellar ataxia, autosomal recessive 24, autosomal recessive cerebellar ataxia - epilepsy - intellectual disability syndrome, autosomal recessive congenital cerebellar ataxia, autosomal recessive metabolic cerebellar ataxia, autosomal recessive degenerative and progressive cerebellar ataxia, autosomal recessive syndromic cerebellar ataxia, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy, spinocerebellar ataxia, autosomal recessive 29, spinocerebellar ataxia, autosomal recessive 30, spinocerebellar ataxia, autosomal recessive 27, spinocerebellar ataxia, autosomal recessive 28, spinocerebellar ataxia, autosomal recessive 25, spinocerebellar ataxia, autosomal recessive 26, spinocerebellar ataxia, autosomal recessive 32, spinocerebellar ataxia, autosomal recessive 33

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

17 retrieved; paginated sample, class counts are floors:

7 pathogenic, 6 uncertain significance, 1 pathogenic/likely pathogenic, 1 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177578	NM_001349232.2(ATG7):c.1727G>A (p.Arg576His)	ATG7	Pathogenic	no assertion criteria provided
1177579	NM_001349232.2(ATG7):c.1870C>T (p.His624Tyr)	ATG7	Pathogenic	no assertion criteria provided
1177580	NM_001349232.2(ATG7):c.782A>G (p.Gln261Arg)	ATG7	Pathogenic	no assertion criteria provided
1177581	NM_001349232.2(ATG7):c.1532G>A (p.Gly511Asp)	ATG7	Pathogenic	no assertion criteria provided
1177583	NM_001349232.2(ATG7):c.1975C>T (p.Arg659Ter)	ATG7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1177584	NM_001349232.2(ATG7):c.2080-2A>G	ATG7	Pathogenic	no assertion criteria provided
3375357	NM_001349232.2(ATG7):c.339G>A (p.Trp113Ter)	ATG7	Pathogenic	criteria provided, single submitter
4071990	NM_001349232.2(ATG7):c.528+3A>G	ATG7	Pathogenic	criteria provided, single submitter
4292912	NM_001349232.2(ATG7):c.1480-2A>T	ATG7	Likely pathogenic	criteria provided, single submitter
1677281	NM_001349232.2(ATG7):c.1277C>T (p.Pro426Leu)	ATG7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1177582	NM_001349232.2(ATG7):c.1535T>C (p.Leu512Pro)	ATG7	Uncertain significance	criteria provided, single submitter
3065403	NM_001349232.2(ATG7):c.899A>T (p.Lys300Ile)	ATG7	Uncertain significance	criteria provided, single submitter
3067898	NM_001349232.2(ATG7):c.1478A>G (p.Lys493Arg)	ATG7	Uncertain significance	criteria provided, single submitter
3067968	NM_001349232.2(ATG7):c.1532G>C (p.Gly511Ala)	ATG7	Uncertain significance	criteria provided, single submitter
3220912	NM_001349232.2(ATG7):c.1186G>A (p.Val396Met)	ATG7	Uncertain significance	criteria provided, single submitter
3362747	NM_001349232.2(ATG7):c.280G>A (p.Glu94Lys)	ATG7	Uncertain significance	criteria provided, single submitter
1677280	NM_001349232.2(ATG7):c.1412T>C (p.Val471Ala)	ATG7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
ATG7	Strong	Autosomal recessive	spinocerebellar ataxia, autosomal recessive 31	4

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
ATG7	HGNC:16935	ENSG00000197548	O95352	Ubiquitin-like modifier-activating enzyme ATG7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATG7	Ubiquitin-like modifier-activating enzyme ATG7	E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATG7	Other/Unknown	no		ThiF_NAD_FAD-bd, Atg7, Atg7_N

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATG7	232	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATG7	5,169

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATG7	O95352	88.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Dengue Virus Attachment and Entry	1	259.6×	0.022	ATG7
Oncogenic MAPK signaling	1	248.3×	0.022	ATG7
Signaling by BRAF and RAF1 fusions	1	170.4×	0.022	ATG7
Autophagy	1	148.3×	0.022	ATG7
Macroautophagy	1	115.3×	0.023	ATG7
Class I MHC mediated antigen processing & presentation	1	70.1×	0.031	ATG7
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.033	ATG7
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.044	ATG7
Adaptive Immune System	1	29.8×	0.048	ATG7
Innate Immune System	1	25.5×	0.051	ATG7
Neutrophil degranulation	1	23.1×	0.051	ATG7
Disease	1	13.1×	0.077	ATG7
Immune System	1	13.0×	0.077	ATG7

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
positive regulation of protein modification process	1	8426.0×	0.001	ATG7
protein modification by small protein conjugation	1	5617.3×	0.001	ATG7
protein lipidation	1	3370.4×	0.001	ATG7
cellular response to hyperoxia	1	3370.4×	0.001	ATG7
cellular response to nitrogen starvation	1	1532.0×	0.002	ATG7
piecemeal microautophagy of the nucleus	1	936.2×	0.003	ATG7
cellular response to stress	1	842.6×	0.003	ATG7
mitophagy	1	318.0×	0.007	ATG7
regulation of circadian rhythm	1	259.3×	0.007	ATG7
rhythmic process	1	251.5×	0.007	ATG7
macroautophagy	1	240.7×	0.007	ATG7
autophagosome assembly	1	224.7×	0.007	ATG7
positive regulation of protein catabolic process	1	203.0×	0.007	ATG7
cellular response to starvation	1	193.7×	0.007	ATG7
autophagy	1	110.1×	0.011	ATG7
defense response to virus	1	69.3×	0.016	ATG7
positive regulation of apoptotic process	1	56.7×	0.019	ATG7
protein transport	1	43.9×	0.023	ATG7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATG7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ATG7	12	Binding:12

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	ATG7

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)
ATG7	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.