TSPOAP1

Chr 17AR

TSPO associated protein 1

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

NCBI Gene: 9256 ENSG00000005379 UniProt: O95153 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

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

6 unique Pathogenic / Likely Pathogenic· 33 VUS of 99 total submissions

Explore recent and relevant literature in Research Assistant →

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 OE?0.25 (0.18–0.36)

0≤0.351.4

Missense OE?0.87 (0.83–0.92)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 23 / 90.2Missense obs/exp: 942 / 1078.7Syn Z: 0.46

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic3

VUS33

Likely Benign21

Benign12

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	0	0	0	3
Likely Pathogenic	3	0	0	0	3
VUS	0	32	1	0	33
Likely Benign	0	9	2	10	21
Benign	0	7	1	4	12
Total	6	48	4	14	72

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap TSPOAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →