TOR2A

Chr 9

torsin family 2 member A

Also known as: TORP1

NCBI Gene: 27433 ENSG00000160404 UniProt: Q5JU69 OMIM: 608052

This gene encodes an AAA family ATPase with similarity to Clp proteases and heat shock proteins, and produces salusin peptides that regulate blood pressure and have antimicrobial properties. Mutations cause autosomal recessive dystonia-26 with infantile onset, characterized by early-onset generalized dystonia and developmental delays. The gene shows moderate tolerance to loss-of-function variants based on population genetics data.

OMIM ResearchSummary from RefSeq

This gene encodes a member of the AAA family of adenosine triphosphatases with similarity to Clp proteases and heat shock proteins. Alternative splicing at this locus results in the translation of multiple isoforms of the encoded protein, some of which contain salusin peptides in the C-terminal region. These peptides may play roles in hypotension, myocardial growth and the induction of mitogenesis, and may also be involved in the pathogenesis of atherosclerosis. The antimicrobial peptide salusin-beta has antibacterial activity. [provided by RefSeq, Nov 2014]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.136

Z-score 2.03

OE 0.30 (0.14–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.25Z-score

OE missense 0.95 (0.84–1.07)

181 obs / 190.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.14–0.78)

0≤0.351.4

Missense OE?0.95 (0.84–1.07)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 9.9Missense obs/exp: 181 / 190.6Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in TOR2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

560 rare PASS variants

Rare truncating (LoF)

1 in 440

73 rare PASS variants

Rare synonymous (reference)

1 in 250

201 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TOR2A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 400
South Asian	~43k	1 in 70	1 in 1,600
Remaining (unassigned)	~30k	1 in 66	1 in 540
European (Finnish)	~27k	1 in 220	1 in 1,100
Admixed American	~22k	1 in 72	1 in 690
African / African American	~21k	1 in 100	1 in 960
East Asian	~20k	1 in 140	1 in 860
Ashkenazi Jewish	~13k	1 in 180	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 72	≈ 1 in 1,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓