TSPOAP1

Chr 17AR

TSPO associated protein 1

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

NCBI Gene: 9256ENSG00000005379UniProt: O95153OMIM: 610764

This protein is required for synaptic transmission regulation and controls the recruitment of voltage-gated calcium channels to the presynaptic membrane, modulating neurotransmitter release. Mutations cause dystonia 22 with either juvenile-onset or adult-onset presentations, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.36), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.362 OMIM phenotypes
Clinical Summary— TSPOAP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 33 VUS of 113 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
1.48Z-score
OE missense 0.87 (0.83–0.92)
942 obs / 1078.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.18–0.36)
0≤0.351.4
Missense OE0.87 (0.83–0.92)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 23 / 90.2Missense obs/exp: 942 / 1078.7Syn Z: 0.46

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic3
VUS33
Likely Benign21
Benign12
17
Pathogenic
3
Likely Pathogenic
33
VUS
21
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
13
0
17
Likely Pathogenic
2
0
1
0
3
VUS
0
31
2
0
33
Likely Benign
0
9
2
10
21
Benign
0
7
1
4
12
Total647191486

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients