Spinocerebellar ataxia 49
diseaseOn this page
Also known as SCA49
Summary
Spinocerebellar ataxia 49 (MONDO:0030805) is a disease with 1 cohort gene.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Cohort genes: 1
- ClinVar variants: 40
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 9 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | spinocerebellar ataxia 49 |
| Mondo ID | MONDO:0030805 |
| OMIM | 619806 |
| Orphanet | 631106 |
| UMLS | C5676950 |
| MedGen | 1805601 |
| GARD | 0025640 |
| Is cancer (heuristic) | no |
Also known as: SCA49 · spinocerebellar ataxia 49
Data availability: 40 ClinVar variants · 1 GenCC gene-disease record.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant cerebellar ataxia › spinocerebellar ataxia 49
Related subtypes (15): GRID2-related autosomal dominant spinocerebellar ataxia, spinocerebellar ataxia 27A, spinocerebellar ataxia 9, spinocerebellar ataxia 43, spinocerebellar ataxia 7, autosomal dominant cerebellar ataxia type I, autosomal dominant cerebellar ataxia type III, autosomal dominant cerebellar ataxia type IV, spinocerebellar ataxia 48, spinocerebellar ataxia 44, spinocerebellar ataxia 47, spinocerebellar ataxia 50, spinocerebellar ataxia 27B, late-onset, spinocerebellar ataxia 51, spinocerebellar ataxia 52
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
40 retrieved; paginated sample, class counts are floors:
22 uncertain significance, 11 conflicting classifications of pathogenicity, 5 benign/likely benign, 1 benign, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 4056350 | NM_152703.5(SAMD9L):c.1618A>G (p.Arg540Gly) | SAMD9L | Likely pathogenic | no assertion criteria provided |
| 1017243 | NM_152703.5(SAMD9L):c.4082T>C (p.Val1361Ala) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1038336 | NM_152703.5(SAMD9L):c.1549T>C (p.Trp517Arg) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1049582 | NM_152703.5(SAMD9L):c.2069G>A (p.Gly690Asp) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1049620 | NM_152703.5(SAMD9L):c.2528G>A (p.Arg843Gln) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1063306 | NM_152703.5(SAMD9L):c.854G>A (p.Arg285Gln) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1520277 | NM_152703.5(SAMD9L):c.4646T>C (p.Ile1549Thr) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3617459 | NM_152703.5(SAMD9L):c.2482C>T (p.Arg828Ter) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 432926 | NM_152703.5(SAMD9L):c.1877C>T (p.Ser626Leu) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 624284 | NM_152703.5(SAMD9L):c.3353A>G (p.Tyr1118Cys) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 774190 | NM_152703.5(SAMD9L):c.1216C>T (p.Arg406Ter) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 813694 | NM_152703.5(SAMD9L):c.2114A>G (p.Tyr705Cys) | SAMD9L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1015386 | NM_152703.5(SAMD9L):c.3568G>C (p.Asp1190His) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1174639 | NM_152703.5(SAMD9L):c.4140dup (p.Gln1381fs) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1316334 | NM_152703.5(SAMD9L):c.1934T>A (p.Leu645Gln) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1320750 | NM_152703.5(SAMD9L):c.987del (p.Asp330fs) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1365897 | NM_152703.5(SAMD9L):c.683G>A (p.Cys228Tyr) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1406139 | NM_152703.5(SAMD9L):c.944T>G (p.Ile315Arg) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1407336 | NM_152703.5(SAMD9L):c.1364T>C (p.Val455Ala) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1410128 | NM_152703.5(SAMD9L):c.1957T>A (p.Leu653Met) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1426492 | NM_152703.5(SAMD9L):c.3410G>A (p.Gly1137Glu) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1705666 | NM_152703.5(SAMD9L):c.499C>A (p.Pro167Thr) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1922426 | NM_152703.5(SAMD9L):c.853C>T (p.Arg285Trp) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1959197 | NM_152703.5(SAMD9L):c.1096T>C (p.Phe366Leu) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2136077 | NM_152703.5(SAMD9L):c.4540A>G (p.Lys1514Glu) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2163451 | NM_152703.5(SAMD9L):c.994dup (p.Ile332fs) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2429769 | NM_152703.5(SAMD9L):c.3932A>T (p.Asp1311Val) | SAMD9L | Uncertain significance | criteria provided, single submitter |
| 3594950 | NM_152703.5(SAMD9L):c.4674_4675del (p.Ser1558fs) | SAMD9L | Uncertain significance | criteria provided, single submitter |
| 3594951 | NM_152703.5(SAMD9L):c.2345T>G (p.Ile782Ser) | SAMD9L | Uncertain significance | criteria provided, single submitter |
| 3594952 | NM_152703.5(SAMD9L):c.757A>G (p.Lys253Glu) | SAMD9L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · Orphanet: 3 · 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 |
|---|---|---|---|---|
| SAMD9L | Definitive | Autosomal dominant | ataxia-pancytopenia syndrome | 7 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SAMD9L | Orphanet:2585 | Ataxia-pancytopenia syndrome |
| SAMD9L | Orphanet:619367 | SAMD9L-associated autoinflammatory syndrome |
| SAMD9L | Orphanet:631106 | Spinocerebellar ataxia type 49 |
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 |
|---|---|---|---|---|---|
| SAMD9L | HGNC:1349 | ENSG00000177409 | Q8IVG5 | Sterile alpha motif domain-containing protein 9-like | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SAMD9L | Sterile alpha motif domain-containing protein 9-like | May be involved in endosome fusion. |
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) |
|---|---|---|---|---|
| SAMD9L | Other/Unknown | no | SAM, SAM/pointed_sf |
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 |
|---|---|
| buccal mucosa cell | 1 |
| leukocyte | 1 |
| pancreatic ductal cell | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SAMD9L | 231 | ubiquitous | marker | pancreatic ductal cell, buccal mucosa cell, leukocyte |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SAMD9L | 1,608 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| SAMD9L | Q8IVG5 | 83.85 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|
| SAMD9L | 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 | SAMD9L |
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) |
|---|---|---|
| SAMD9L | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: SAMD9L