TSPOAP1

Chr 17AR

TSPO associated protein 1

Also known as: BZRAP1, DYT22, PBR-IP, PRAX-1, PRAX1, RIM-BP1, RIMBP1

NCBI Gene: 9256ENSG00000005379UniProt: O95153

Enables benzodiazepine receptor binding activity. Involved in regulation of neurotransmitter secretion. Located in mitochondrion. Implicated in dystonia 22, adult-onset and dystonia 22, juvenile-onset. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

?Dystonia 22, adult-onsetMIM #620456
AR
Dystonia 22, juvenile-onsetMIM #620453
AR
74
ClinVar variants
19
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— TSPOAP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 26 VUS of 74 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.36LOEUF
pLI 0.008
Z-score 6.56
OE 0.25 (0.18–0.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.48Z-score
OE missense 0.87 (0.83–0.92)
942 obs / 1078.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.18–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.83–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 23 / 90.2Missense obs/exp: 942 / 1078.7Syn Z: 0.46

ClinVar Variant Classifications

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS26
Likely Benign17
Benign12
17
Pathogenic
2
Likely Pathogenic
26
VUS
17
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
15
0
17
Likely Pathogenic
1
0
1
0
2
VUS
0
25
1
0
26
Likely Benign
0
6
2
9
17
Benign
0
7
1
4
12
Total338201374

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TSPOAP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Dystonia 22, adult-onset

MIM #620456

Molecular basis of disorder known

Autosomal recessive

Dystonia 22, juvenile-onset

MIM #620453

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Blood transcriptome sequencing identifies biomarkers able to track disease stages in spinocerebellar ataxia type 3.
Raposo M et al.·Brain
2023
Shared genetic risk loci between Alzheimer's disease and related dementias, Parkinson's disease, and amyotrophic lateral sclerosis.
Wainberg M et al.·Alzheimers Res Ther
2023
Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, cause autosomal recessive dystonia.
Mencacci NE et al.·J Clin Invest
2021
Clinical and genetic profile of patients with dystonia: An experience from a tertiary neurology center from India.
Dhar D et al.·Parkinsonism Relat Disord
2024Cohort
Mutation profile of Bardet-Biedl syndrome patients from India: Implicative role of multiallelic rare variants and oligogenic inheritance pattern.
Gnanasekaran H et al.·Clin Genet
2023Cohort
Expanding the genotypic and phenotypic spectrum of DYT-TSPOAP1: First report from India.
Holla VV et al.·Parkinsonism Relat Disord
2026Case report
Dissecting genetic architecture of rare dystonia: genetic, molecular and clinical insights.
Atasu B et al.·J Med Genet
2024
Deep Brain Stimulation in a Patient with TSPOAP1-Biallelic Variant of Autosomal-Recessive Dystonia.
Hasani E et al.·Mov Disord
2023Case report
Region-Based Analysis with Functional Annotation Identifies Genes Associated with Cognitive Function in South Asians from India.
Abu-Amara H et al.·Genes (Basel)
2025Functional
Gene expression in the corneal endothelium of Fuchs endothelial corneal dystrophy patients with and without expansion of a trinucleotide repeat in TCF4.
Wieben ED et al.·PLoS One
2018Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools