TSPOAP1

protein-coding

TSPO associated protein 1, the group of Fibronectin type III domain containing

Gene summary

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]

Previous symbols:

BZRAP1

MANE transcript

NM_004758.4

Inheritance

ClinVar variants

P:7U:46B:29

Top phenotype

Dystonia 22, juvenile-onset; Dystonia 22, adult-onset

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr17:58,301,228-58,328,795

External References & Databases

Ensembl (ENSG00000005379)

Transcript & Mutation Effects

hg38 • Region Span ~27.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dystonia 22, juvenile-onsetSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957539

Submitter: PanelApp Australia

TH-deficient dopa-responsive dystoniaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011551

Submitter: Orphanet

Clinical Genomic Database (CGD)

Dystonia 22, juvenile-onset; Dystonia 22, adult-onsetAR

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Individuals have been described as responding to some medications used to treat dystonia (eg, clonazepam, phenytoin), but not other medications, and awareness may enable tailored medical management

Refs: 33539324

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TSPOAP1 variants in ClinVar

11 Conditions Cataloged

not providedTotal: 42

not specifiedTotal: 23

Dystonia 22, juvenile-onsetTotal: 7

Dystonia 22, adult-onsetTotal: 4

TSPOAP1-related disorderTotal: 2

Bardet-Biedl syndromeTotal: 2

TSPOAP1-related DystoniaTotal: 2

Juvenile-onset progressive generalized dystoniaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004758.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	11 clinvar	3 clinvar	17
missense			41 clinvar	10 clinvar	5 clinvar	56
nonsense	2 clinvar	1 clinvar				3
start loss						0
frameshift	2 clinvar	2 clinvar				4
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	4	3	46	21	8	82

Highest pathogenic variant AF is 0.0000061567844

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004758.4	RefSeq	NP_004749.2	31	MANE Select
ENST00000343736.9	Ensembl	ENSP00000345824.4	31	MANE Select
NM_001261835.2	RefSeq	NP_001248764.1	31	Standard
NM_024418.3	RefSeq	NP_077729.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Benzodiazepine Pathway, Pharmacodynamics
Metabolism of lipids
Metabolism
Pregnenolone biosynthesis
Neuronal System

Biological Process

C21-steroid hormone biosynthetic process
neuromuscular synaptic transmission
biological_process
regulation of presynaptic cytosolic calcium ion concentration

Molecular Function

protein binding
benzodiazepine receptor binding
voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels

Cellular Component

cytoplasm
mitochondrion
cytosol
calyx of Held
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343736
Coding exons: 31
Length: 27561
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125748
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.48	942	1.08e+3	0.873	0.0000653	11732
Missense (PolyPhen)		217	289.63	0.74924		3352
Synonymous	0.464	446	459	0.972	0.0000279	3974
Loss of Function	6.56	23	90.2	0.255	0.00000519	963

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.125

Intolerance Scores

RVIS EVS: 2.28
RVIS percentile EVS: 98.27

Essentials

Essential (gene trap): N