SPG7

Chr 16AR

SPG7 matrix AAA peptidase subunit, paraplegin

Also known as: CAR, CMAR, PGN, SPG5C

The protein is a mitochondrial metalloprotease that functions in the inner mitochondrial membrane and belongs to the AAA family involved in proteolysis, protein folding, and organelle biogenesis. Mutations cause autosomal recessive spastic paraplegia 7, characterized by progressive spasticity and weakness of the lower limbs. The pathogenic mechanism involves dominant negative effects disrupting normal mitochondrial protease function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 1.652 OMIM phenotypes
Clinical SummarySPG7
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — SPG7
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.65LOEUF
pLI 0.000
Z-score -1.69
OE 1.30 (1.031.65)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.87Z-score
OE missense 1.11 (1.031.20)
528 obs / 474.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.30 (1.031.65)
00.351.4
Missense OE1.11 (1.031.20)
00.61.4
Synonymous OE1.38
01.21.6
LoF obs/exp: 48 / 36.9Missense obs/exp: 528 / 474.5Syn Z: -4.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSPG7-related spastic paraplegiaOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.5661th %ile
LOF
0.3744th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SPG7 · 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

No active trials found for this gene.

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Clinical Literature
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