SPG11

Chr 15AR

SPG11 vesicle trafficking associated, spatacsin

Also known as: ALS5, CMT2X, KIAA1840

NCBI Gene: 80208ENSG00000104133UniProt: Q96JI7OMIM: 604360

The protein encoded by SPG11 is a transmembrane protein that becomes phosphorylated in response to DNA damage and localizes to the cytoplasm and cytosol. Mutations cause autosomal recessive spastic paraplegia type 11, juvenile amyotrophic lateral sclerosis type 5, and axonal Charcot-Marie-Tooth disease type 2X. The pathogenic mechanism involves disruption of the protein's response to DNA damage, leading to progressive neurodegeneration affecting motor neurons and peripheral nerves.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.814 OMIM phenotypes
Clinical Summary— SPG11
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Gene-Disease Validity (ClinGen)
hereditary spastic paraplegia 11 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
75 unique Pathogenic / Likely Pathogenic· 3 VUS of 200 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — SPG11
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 3.30
OE 0.67 (0.56–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.39Z-score
OE missense 1.11 (1.06–1.16)
1360 obs / 1223.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.67 (0.56–0.81)
0≤0.351.4
Missense OE1.11 (1.06–1.16)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 81 / 120.0Missense obs/exp: 1360 / 1223.0Syn Z: -2.17

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic18
VUS3
Likely Benign85
Benign6
Conflicting7
57
Pathogenic
18
Likely Pathogenic
3
VUS
85
Likely Benign
6
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
51
2
4
0
57
Likely Pathogenic
16
1
1
0
18
VUS
0
3
0
0
3
Likely Benign
0
1
46
38
85
Benign
0
1
4
1
6
Conflicting
—7
Total6785539176

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

View in ClinVar →

Protein Context — Lollipop Plot

SPG11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients