Striatal degeneration, autosomal dominant 2
diseaseOn this page
Also known as ADSD2PDE10A striatal degeneration, autosomal dominantstriatal degeneration, autosomal dominantstriatal degeneration, autosomal dominant 2striatal degeneration, autosomal dominant caused by mutation in PDE10Astriatal Degeneration, autosomal dominant type 2
Summary
Striatal degeneration, autosomal dominant 2 (MONDO:0014835) is a disease caused by PDE10A (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: PDE10A (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 10
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | striatal degeneration, autosomal dominant 2 |
| Mondo ID | MONDO:0014835 |
| OMIM | 616922 |
| DOID | DOID:0060998 |
| UMLS | C4310791 |
| MedGen | 934758 |
| GARD | 0025021 |
| Is cancer (heuristic) | no |
Also known as: ADSD2 · PDE10A striatal degeneration, autosomal dominant · striatal degeneration, autosomal dominant · striatal Degeneration, autosomal dominant 2 · striatal degeneration, autosomal dominant 2; ADSD2 · striatal degeneration, autosomal dominant caused by mutation in PDE10A · striatal Degeneration, autosomal dominant type 2
Data availability: 10 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › synucleinopathy › multiple system atrophy › striatonigral degeneration › striatal degeneration, autosomal dominant › striatal degeneration, autosomal dominant 2
Related subtypes (1): autosomal dominant striatal neurodegeneration type 1
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
10 retrieved; paginated sample, class counts are floors:
3 uncertain significance, 2 benign, 2 pathogenic, 1 pathogenic/likely pathogenic, 1 likely benign, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 225635 | NM_001385079.1(PDE10A):c.1798T>C (p.Phe600Leu) | PDE10A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 225636 | NM_001385079.1(PDE10A):c.1696T>C (p.Phe566Leu) | PDE10A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 522607 | NM_001385079.1(PDE10A):c.1799T>G (p.Phe600Cys) | PDE10A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 804399 | NM_001385079.1(PDE10A):c.1342C>T (p.Arg448Ter) | PDE10A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1339004 | NM_001385079.1(PDE10A):c.863C>A (p.Pro288His) | PDE10A | Uncertain significance | criteria provided, single submitter |
| 4279792 | NM_001385079.1(PDE10A):c.1136T>C (p.Ile379Thr) | PDE10A | Uncertain significance | criteria provided, single submitter |
| 4540433 | NM_001385079.1(PDE10A):c.2895+2T>C | PDE10A | Uncertain significance | criteria provided, single submitter |
| 1164211 | NM_001385079.1(PDE10A):c.1692G>A (p.Ala564=) | PDE10A | Benign | criteria provided, multiple submitters, no conflicts |
| 1168261 | NM_001385079.1(PDE10A):c.1890-19T>C | PDE10A | Benign | criteria provided, multiple submitters, no conflicts |
| 753219 | NM_001385079.1(PDE10A):c.1155C>T (p.Ala385=) | PDE10A | Likely benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 9 · Orphanet: 2 · 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 |
|---|---|---|---|---|
| PDE10A | Strong | Autosomal dominant | striatal degeneration, autosomal dominant 2 | 9 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PDE10A | Orphanet:494526 | Infantile-onset generalized dyskinesia with orofacial involvement |
| PDE10A | Orphanet:494541 | Childhood-onset benign chorea with striatal involvement |
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 |
|---|---|---|---|---|---|
| PDE10A | HGNC:8772 | ENSG00000112541 | Q9Y233 | cAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodiesterase 10A | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PDE10A | cAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodiesterase 10A | Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. |
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) |
|---|---|---|---|---|
| PDE10A | Transcription factor | no | 3.1.4.17 | PDEase_catalytic_dom, GAF, HD/PDEase_dom |
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 |
| cartilage tissue | 1 |
| left uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PDE10A | 219 | broad | marker | adrenal tissue, left uterine tube, cartilage tissue |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PDE10A | 1,318 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PDE10A | Q9Y233 | 359 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 2. 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 |
|---|---|---|---|---|
| cGMP effects | 1 | 713.8× | 0.003 | PDE10A |
| G alpha (s) signalling events | 1 | 73.2× | 0.014 | PDE10A |
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 |
|---|---|---|---|---|
| cGMP catabolic process | 1 | 3370.4× | 7e-04 | PDE10A |
| regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway | 1 | 3370.4× | 7e-04 | PDE10A |
| negative regulation of receptor guanylyl cyclase signaling pathway | 1 | 2808.7× | 7e-04 | PDE10A |
| cAMP catabolic process | 1 | 1872.4× | 8e-04 | PDE10A |
| negative regulation of cAMP/PKA signal transduction | 1 | 601.9× | 0.002 | PDE10A |
| signal transduction | 1 | 16.1× | 0.062 | PDE10A |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| PDE10A | VARDENAFIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PDE10A | 16 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| VARDENAFIL | 4 | PDE10A |
| SILDENAFIL | 4 | PDE10A |
| CINCHOPHEN | 4 | PDE10A |
| DIPYRIDAMOLE | 4 | PDE10A |
| PAPAVERINE | 3 | PDE10A |
| OXYCINCHOPHEN | 2 | PDE10A |
| ZAPRINAST | 2 | PDE10A |
| PF-06835919 | 2 | PDE10A |
| MK-8189 | 2 | PDE10A |
| MARDEPODECT | 2 | PDE10A |
| PAPAVERINE HYDROCHLORIDE | 2 | PDE10A |
| PF-04217903 | 1 | PDE10A |
| JNJ-42396302 | 1 | PDE10A |
| LENRISPODUN PHOSPHATE | 1 | PDE10A |
| PBF-999 | 1 | PDE10A |
| AZD-7687 | 1 | PDE10A |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PDE10A | 357 | Binding:345, ADMET:9, Functional:3 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PDE10A | 3.1.4.17 | 3’,5’-cyclic-nucleotide phosphodiesterase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| PDE10A | 357 |
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
16 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| VARDENAFIL | 4 | PDE10A |
| SILDENAFIL | 4 | PDE10A |
| CINCHOPHEN | 4 | PDE10A |
| DIPYRIDAMOLE | 4 | PDE10A |
| PAPAVERINE | 3 | PDE10A |
| OXYCINCHOPHEN | 2 | PDE10A |
| ZAPRINAST | 2 | PDE10A |
| PF-06835919 | 2 | PDE10A |
| MK-8189 | 2 | PDE10A |
| MARDEPODECT | 2 | PDE10A |
| PAPAVERINE HYDROCHLORIDE | 2 | PDE10A |
| PF-04217903 | 1 | PDE10A |
| JNJ-42396302 | 1 | PDE10A |
| LENRISPODUN PHOSPHATE | 1 | PDE10A |
| PBF-999 | 1 | PDE10A |
| AZD-7687 | 1 | PDE10A |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | PDE10A |
| 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 | 0 |
Undrugged target profiles
0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
Clinical trials & evidence
Clinical trials
Clinical trials: 0.