X-linked dystonia-parkinsonism

Summary

X-linked dystonia-parkinsonism (MONDO:0010747) is a disease caused by TAF1 (GenCC Strong), with 1 cohort gene and 3 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: TAF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19
• Phenotypes (HPO): 19
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Validated
Point prevalence	1-9 / 1 000 000	0.31	Philippines	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0000643	Blepharospasm	Frequent (30-79%)
HP:0001304	Torsion dystonia	Frequent (30-79%)
HP:0001336	Myoclonus	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002072	Chorea	Frequent (30-79%)
HP:0002172	Postural instability	Frequent (30-79%)
HP:0002322	Resting tremor	Frequent (30-79%)
HP:0002362	Shuffling gait	Frequent (30-79%)
HP:0002378	Hand tremor	Frequent (30-79%)
HP:0002548	Parkinsonism with favorable response to dopaminergic medication	Frequent (30-79%)
HP:0004373	Focal dystonia	Frequent (30-79%)
HP:0007158	Progressive extrapyramidal muscular rigidity	Frequent (30-79%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0002359	Frequent falls	Occasional (5-29%)
HP:0002451	Limb dystonia	Occasional (5-29%)
HP:0006511	Laryngeal stridor	Occasional (5-29%)
HP:0010808	Protruding tongue	Occasional (5-29%)
HP:0011951	Aspiration pneumonia	Occasional (5-29%)
HP:0031162	Impaired oropharyngeal swallow response	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked dystonia-parkinsonism
Mondo ID	MONDO:0010747
MeSH	C564048
OMIM	314250
Orphanet	53351
DOID	DOID:0090057
NCIT	C126330
SNOMED CT	698279003
UMLS	C1839130
MedGen	326820
GARD	0010533
Is cancer (heuristic)	no

Also known as: dystonia 3, torsion, X-linked · dystonia-Parkinsonism, X-linked, X-linked recessive · DYT-TAF1 · DYT3 · Lubag · Lubag syndrome · X-linked dystonia Parkinsonism · X-linked dystonia-Parkinsonism syndrome · X-linked dystonia-parkinsonism/Lubag · X-linked torsion dystonia-Parkinsonism syndrome · XDP

Data availability: 19 ClinVar variants · 5 GenCC gene-disease records · 62 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › focal dystonia › X-linked dystonia-parkinsonism

Related subtypes (11): anismus, cervical dystonia, focal hand dystonia, oculogyric crisis, spasmodic dystonia, craniofacial dystonia, torsion dystonia 7, benign essential blepharospasm, dystonia 23, oromandibular dystonia, dystonia, focal, task-specific

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

19 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
9862	NG_012771.2:g.79230_79231ins[AB191243.1:g.261508_264134]	TAF1	Pathogenic	no assertion criteria provided
1339839	NM_004606.5(TAF1):c.235+3G>A	TAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028275	NM_004606.5(TAF1):c.1474A>T (p.Met492Leu)	TAF1	Uncertain significance	criteria provided, single submitter
1344723	NM_004606.5(TAF1):c.3796G>A (p.Gly1266Arg)	TAF1	Uncertain significance	criteria provided, single submitter
1704666	NM_004606.5(TAF1):c.2267A>G (p.His756Arg)	TAF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
21011	NR_104387.1(TAF1):n.5894C>T	TAF1	Uncertain significance	criteria provided, single submitter
2441649	NM_004606.5(TAF1):c.1632G>T (p.Gly544=)	TAF1	Uncertain significance	criteria provided, single submitter
2692327	NM_004606.5(TAF1):c.2551G>A (p.Ala851Thr)	TAF1	Uncertain significance	criteria provided, single submitter
3065630	NM_004606.5(TAF1):c.2327A>G (p.Glu776Gly)	TAF1	Uncertain significance	criteria provided, single submitter
3393244	NM_004606.5(TAF1):c.694C>A (p.Pro232Thr)	TAF1	Uncertain significance	criteria provided, single submitter
417915	NM_004606.5(TAF1):c.4427A>C (p.Asp1476Ala)	TAF1	Uncertain significance	criteria provided, single submitter
4278354	NM_004606.5(TAF1):c.905C>T (p.Pro302Leu)	TAF1	Uncertain significance	criteria provided, single submitter
4531225	NM_004606.5(TAF1):c.4265T>G (p.Ile1422Ser)	TAF1	Uncertain significance	criteria provided, single submitter
695493	NM_004606.5(TAF1):c.4754-4A>G	TAF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
695775	NM_004606.5(TAF1):c.4698G>A (p.Arg1566=)	TAF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
696096	NM_004606.5(TAF1):c.4708C>T (p.Leu1570=)	TAF1	Benign	criteria provided, multiple submitters, no conflicts
697120	NM_004606.5(TAF1):c.422C>T (p.Pro141Leu)	TAF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
698491	NM_004606.5(TAF1):c.4521G>A (p.Ala1507=)	TAF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
700214	NM_004606.5(TAF1):c.4155G>A (p.Thr1385=)	TAF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · 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
TAF1	Definitive	X-linked	intellectual disability, X-linked, syndromic 33	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TAF1	Orphanet:480907	X-linked intellectual disability-global development delay-facial dysmorphism-sacral caudal remnant syndrome
TAF1	Orphanet:53351	X-linked dystonia-parkinsonism

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
TAF1	HGNC:11535	ENSG00000147133	P21675	Transcription initiation factor TFIID subunit 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TAF1	Transcription initiation factor TFIID subunit 1	The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.

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)
TAF1	Transcription factor	no	2.3.1.48	Bromodomain, TAF_II_230-bd, TAF1_animal

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
calcaneal tendon	1
sural nerve	1
tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TAF1	262	ubiquitous	marker	sural nerve, calcaneal tendon, tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TAF1	3,445

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TAF1	P21675	64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. 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
HIV Transcription Initiation	1	233.1×	0.013	TAF1
RNA Polymerase II HIV Promoter Escape	1	233.1×	0.013	TAF1
RNA Polymerase II Promoter Escape	1	233.1×	0.013	TAF1
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	1	233.1×	0.013	TAF1
RNA Polymerase II Transcription Initiation	1	233.1×	0.013	TAF1
RNA Polymerase II Transcription Initiation And Promoter Clearance	1	233.1×	0.013	TAF1
Transcription of the HIV genome	1	173.0×	0.013	TAF1
Late Phase of HIV Life Cycle	1	167.9×	0.013	TAF1
HIV Life Cycle	1	160.8×	0.013	TAF1
RNA Polymerase II Pre-transcription Events	1	137.6×	0.013	TAF1
Regulation of TP53 Activity	1	132.8×	0.013	TAF1
HIV Infection	1	119.0×	0.013	TAF1
Regulation of TP53 Activity through Phosphorylation	1	117.7×	0.013	TAF1
Transcriptional Regulation by TP53	1	62.1×	0.023	TAF1
Viral Infection Pathways	1	30.8×	0.043	TAF1
Infectious disease	1	24.8×	0.050	TAF1
RNA Polymerase II Transcription	1	22.5×	0.052	TAF1
Gene expression (Transcription)	1	17.8×	0.062	TAF1
Generic Transcription Pathway	1	15.1×	0.070	TAF1
Disease	1	13.1×	0.076	TAF1

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 androgen receptor signaling pathway	1	16852.0×	0.001	TAF1
negative regulation of protein autoubiquitination	1	8426.0×	0.001	TAF1
transcription initiation at RNA polymerase I promoter	1	1872.4×	0.004	TAF1
regulation of cell cycle G1/S phase transition	1	1532.0×	0.004	TAF1
negative regulation of signal transduction by p53 class mediator	1	1203.7×	0.004	TAF1
cellular response to ATP	1	887.0×	0.004	TAF1
negative regulation of ubiquitin-dependent protein catabolic process	1	842.6×	0.004	TAF1
midbrain development	1	601.9×	0.005	TAF1
regulation of signal transduction by p53 class mediator	1	383.0×	0.006	TAF1
transcription initiation at RNA polymerase II promoter	1	374.5×	0.006	TAF1
mRNA transcription by RNA polymerase II	1	330.4×	0.006	TAF1
cellular response to UV	1	295.6×	0.006	TAF1
RNA polymerase II preinitiation complex assembly	1	271.8×	0.006	TAF1
positive regulation of transcription initiation by RNA polymerase II	1	271.8×	0.006	TAF1
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	1	210.7×	0.008	TAF1
protein autophosphorylation	1	145.3×	0.010	TAF1
protein polyubiquitination	1	115.4×	0.012	TAF1
ubiquitin-dependent protein catabolic process	1	74.2×	0.017	TAF1
transcription by RNA polymerase II	1	70.5×	0.017	TAF1
negative regulation of gene expression	1	69.1×	0.017	TAF1
protein stabilization	1	66.9×	0.017	TAF1
DNA damage response	1	53.5×	0.020	TAF1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.059	TAF1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	TAF1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TAF1	3	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERALASERTIB	3	TAF1
BI-2536	2	TAF1
AZD-5153	1	TAF1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TAF1	140	Binding:139, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TAF1	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TAF1	140

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

3 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)
CERALASERTIB	3	TAF1
BI-2536	2	TAF1
AZD-5153	1	TAF1

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	1	TAF1
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: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05592028	Not specified	AVAILABLE	High Intensity Focused Ultrasound for X-linked Dystonia-parkinsonism
NCT03019458	Not specified	COMPLETED	MINGO Supplemental Trial in X-linked Dystonia-Parkinsonism Patients
NCT05713721	Not specified	UNKNOWN	Sensorimotor Integration in Monogenic Parkinson-dystonia Syndromes