Curation XDP TAF1

Gene TAF1

Disease XDP

Inheritance XR

Score

9.5 + 4 = 13.5 / 18

Genetic + experimental = total

Classification

Definitive

Refuted

Moderate

Definitive

Last Updated 08/14/2025

Pubs Reviewed 10

Publication Span 29.08 years

Publication Interval 29.08 years

Curator(s) Macayla Weiner, Laurel Hiatt, Elbay Aliyev

Description

X-linked dystonia-parkinsonism (XDP) is an adult-onset, X-linked movement disorder most often affecting males of Filipino/Panay ancestry and associated with a founder SVA retrotransposon insertion in intron 32 of TAF1. The XDP SVA contains a variable (CCCTCT)n hexameric repeat whose length correlates inversely with age at onset and shows tissue-specific somatic instability in brain. Genetic studies support segregation of the XDP haplotype/SVA with disease, while functional studies show SVA-associated TAF1 dysregulation, including reduced TAF1 expression, intron 32 retention/aberrant splicing, and epigenetic effects involving DNA methylation and H3K9me3.

All criTRia Curations Locus Page

Genetic evidence

Total: 9.5

Per page

Category	Type	Citation	Score	Details
Singular Evidence	Probands	PMID:30973967	6	PMID:30973967 enrolled 52 male patients with clinically and genetically confirmed XDP, typical X-linked family history, Panay maternal ancestry, and molecular confirmation of TAF1 haplotype variants; this supports affected-case ascertainment but is not a primary locus-discovery cohort.
Collective Evidence	Allele	PMID:29229810 PMID:38835911 PMID:35395816	2	PMID:29229810 identified polymorphic (CCCTCT)n repeat length within the XDP-specific TAF1 SVA in 140 patients, with 35-52 repeats and a significant inverse correlation with age at onset. PMID:35395816 confirmed repeat-length associations with age at onset/death and showed repeat-length-dependent somatic expansion in blood and brain; PMID:38835911 summarizes repeat length and modifier effects on variable expressivity.
Collective Evidence	Segregation	PMID:29229810 PMID:7668293	1.5	PMID:7668293 found the same DXS7117/DXS7119 haplotype in 42/47 unrelated XDP patients and used linkage disequilibrium to localize DYT3 to Xq13.1. PMID:29229810 reports that affected individuals share the XDP founder haplotype containing the TAF1 SVA and that these variants were not found in ethnically matched or other controls.

Experimental evidence

Total: 4

Per page

Category	Type	Citation	Score	Details
Function	Protein interaction	PMID:38834915	0.5	PMID:38834915 showed that the KRAB zinc-finger protein ZNF91 recognizes SVAs in neural progenitor cells and helps establish H3K9me3/DNA methylation over the polymorphic XDP SVA; this supports a transposon-regulatory protein interaction rather than a direct TAF1 protein-protein interaction.
Function	Regulatory impact	PMID:17273961 PMID:29474918 PMID:30973967	2	PMID:17273961 identified the XDP-specific SVA insertion in TAF1 and reduced TAF1/DRD2 expression plus altered SVA methylation in XDP caudate. PMID:29474918 showed decreased cTAF1, SVA-proximal intron retention/aberrant splicing, and normalization after CRISPR/Cas9 SVA excision. PMID:30973967 provides clinical context only and does not add molecular regulatory evidence.
Functional Alteration	Patient cells	PMID:35868859	0.5	PMID:35868859 characterized eight iPSC lines from three heterozygous female XDP carriers with X-chromosome-inactivation clones expressing either the wild-type or XDP haplotype, providing non-patient carrier cell resources for modeling TAF1/SVA effects.
Functional Alteration	Patient cells	PMID:34250228	1	Repeat sizing and somatic instability in human postmortem brain tissues from two XDP patients showed higher median repeat numbers and higher degrees of repeat instability in the basal ganglia and cerebellum compared with blood.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.