TOR4A

Chr 9

torsin family 4 member A

Also known as: C9orf167

NCBI Gene: 54863 ENSG00000198113 UniProt: Q9NXH8 OMIM: 621477

The protein is predicted to bind and hydrolyze ATP and is predicted to be active in the endoplasmic reticulum lumen and nuclear envelope. Mutations cause autosomal recessive spastic paraplegia-76, a form of hereditary spastic paraplegia affecting the motor system. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.71).

OMIM ResearchSummary from RefSeq

Predicted to enable ATP binding activity and ATP hydrolysis activity. Predicted to be located in extracellular region and platelet alpha granule lumen. Predicted to be active in endoplasmic reticulum lumen and nuclear envelope. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.71

Clinical Summary— TOR4A

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.

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ClinVar Variants

70 VUS of 78 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.71LOEUF

pLI 0.561

Z-score 2.04

OE 0.15 (0.05–0.71)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

2.92Z-score

OE missense 0.53 (0.46–0.60)

159 obs / 301.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.05–0.71)

0≤0.351.4

Missense OE?0.53 (0.46–0.60)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 1 / 6.7Missense obs/exp: 159 / 301.6Syn Z: 1.49

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	70	0	70
Likely Benign	3	3	6
Benign	0	0	0
Total	73	3	76

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

View in ClinVar →

97 pathogenic / likely-pathogenic (of 108) ClinVar copy-number / structural variants overlap TOR4A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →