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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SPG11
SPG11 vesicle trafficking associated, spatacsin
Chromosome 15 Β· 15q21.1
NCBI Gene: 80208Ensembl: ENSG00000104133.16HGNC: HGNC:11226UniProt: A0A804HID9
112PubMed Papers
23Diseases
0Drugs
567Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytosolcytoplasmic vesicleprotein bindingprotein kinase bindingAutosomal recessive spastic paraplegia type 11hereditary spastic paraplegia 11Autosomal recessive Charcot Marie Tooth disease type 2Xamyotrophic lateral sclerosis type 5
✦AI Summary

SPG11 encodes spatacsin, a 280 kDa protein that plays a critical role in vesicle trafficking and autophagy-lysosomal machinery function 1. The protein is essential for maintaining neuronal integrity, particularly affecting the corticospinal tracts and other neuronal populations. SPG11 mutations cause the most frequent form of complex autosomal recessive hereditary spastic paraplegia (SPG11-HSP), representing a significant proportion of hereditary spastic paraplegia cases 2 3. The disorder typically manifests with progressive lower limb weakness and spasticity, but exhibits a heterogeneous phenotype that can include cognitive decline, thin corpus callosum, peripheral neuropathy, and various movement disorders such as dystonia, tremor, and parkinsonism 1 4. SPG11-HSP represents a unique example of a disorder bridging neurodevelopmental and neurodegenerative processes, with spatacsin dysfunction affecting both neuronal development and maintenance 1 5. The protein's involvement in autophagy dysfunction places it within an emerging group of genetic diseases affecting core autophagy machinery components, which share recognizable clinical signatures including neurological, neuromuscular, and multisystem manifestations 5. Disease onset and progression can vary significantly, even among patients with identical mutations 6.

Sources cited
1
Spatacsin is a 280 kDa protein that impacts autophagy-lysosomal machinery and bridges neurodevelopmental and neurodegenerative phenotypes
PMID: 32355960
2
SPG11 is the most frequent autosomal recessive hereditary spastic paraplegia subtype
PMID: 24603320
3
SPG11 represents a significant proportion of hereditary spastic paraplegia cases in clinical practice
PMID: 34983064
4
SPG11-HSP can manifest with various movement disorders including dystonia, tremor, and parkinsonism
PMID: 38035585
5
SPG11 dysfunction is part of congenital disorders of autophagy affecting core autophagy machinery
PMID: 34130600
6
Disease onset and progression can vary significantly even among patients with identical mutations
PMID: 35254204
Disease Associationsβ“˜23
Autosomal recessive spastic paraplegia type 11Open Targets
0.79Strong
hereditary spastic paraplegia 11Open Targets
0.79Strong
Autosomal recessive Charcot Marie Tooth disease type 2XOpen Targets
0.78Strong
amyotrophic lateral sclerosis type 5Open Targets
0.75Strong
hereditary spastic paraplegiaOpen Targets
0.70Moderate
genetic disorderOpen Targets
0.55Moderate
Spastic paraplegiaOpen Targets
0.50Moderate
Abnormal central motor functionOpen Targets
0.49Moderate
metabolic diseaseOpen Targets
0.43Moderate
juvenile amyotrophic lateral sclerosisOpen Targets
0.37Weak
atypical juvenile parkinsonismOpen Targets
0.35Weak
cerebral amyloid angiopathy, APP-relatedOpen Targets
0.34Weak
Spastic paraparesisOpen Targets
0.34Weak
Gait disturbanceOpen Targets
0.33Weak
autism spectrum disorderOpen Targets
0.33Weak
Generalized hyperreflexiaOpen Targets
0.33Weak
Charcot-Marie-Tooth diseaseOpen Targets
0.27Weak
Abnormal brain morphologyOpen Targets
0.27Weak
Alzheimer diseaseOpen Targets
0.26Weak
amyotrophic lateral sclerosisOpen Targets
0.20Weak
Amyotrophic lateral sclerosis 5, juvenileUniProt
Charcot-Marie-Tooth disease, axonal, type 2XUniProt
Spastic paraplegia 11, autosomal recessiveUniProt
Pathogenic Variants567
NM_025137.4(SPG11):c.3311dup (p.Asn1104fs)Pathogenic
not provided|Hereditary spastic paraplegia 11
β˜…β˜…β˜†β˜†2026β†’ Residue 1104
NM_025137.4(SPG11):c.1478_1482del (p.Leu493fs)Pathogenic
Hereditary spastic paraplegia 11|Hereditary spastic paraplegia|SPG11-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 493
NM_025137.4(SPG11):c.733_734del (p.Met245fs)Pathogenic
Hereditary spastic paraplegia 11|Amyotrophic lateral sclerosis type 5|not provided|Hereditary spastic paraplegia|Inborn genetic diseases|Hereditary spastic paraplegia 11;Amyotrophic lateral sclerosis type 5|Charcot-Marie-Tooth disease axonal type 2X|SPG11-related disorder|Cerebral amyloid angiopathy, APP-related|Hereditary spastic paraplegia 11;Charcot-Marie-Tooth disease axonal type 2X;Amyotrophic lateral sclerosis type 5
β˜…β˜…β˜†β˜†2026β†’ Residue 245
NM_025137.4(SPG11):c.6859C>T (p.Gln2287Ter)Pathogenic
Hereditary spastic paraplegia 11;Charcot-Marie-Tooth disease axonal type 2X;Amyotrophic lateral sclerosis type 5|Hereditary spastic paraplegia 11
β˜…β˜…β˜†β˜†2026β†’ Residue 2287
NM_025137.4(SPG11):c.6598A>T (p.Lys2200Ter)Pathogenic
Hereditary spastic paraplegia 11|Hereditary spastic paraplegia|SPG11-related disorder|Early-onset Parkinson disease 20|Amyotrophic lateral sclerosis type 5;Hereditary spastic paraplegia 11;Charcot-Marie-Tooth disease axonal type 2X|not provided|Charcot-Marie-Tooth disease axonal type 2X
β˜…β˜…β˜†β˜†2026β†’ Residue 2200
NM_025137.4(SPG11):c.1085G>A (p.Trp362Ter)Pathogenic
not provided|Hereditary spastic paraplegia 11|Hereditary spastic paraplegia 11;Charcot-Marie-Tooth disease axonal type 2X;Amyotrophic lateral sclerosis type 5|Hereditary spastic paraplegia|Charcot-Marie-Tooth disease axonal type 2X|Amyotrophic lateral sclerosis type 5
β˜…β˜…β˜†β˜†2026β†’ Residue 362
NM_025137.4(SPG11):c.7155T>G (p.Tyr2385Ter)Pathogenic
Hereditary spastic paraplegia 11|Amyotrophic lateral sclerosis type 5|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 2385
NM_025137.4(SPG11):c.1348dup (p.Ile450fs)Pathogenic
Hereditary spastic paraplegia 11|not provided|Amyotrophic lateral sclerosis type 5;Hereditary spastic paraplegia 11;Charcot-Marie-Tooth disease axonal type 2X|Hereditary spastic paraplegia|Charcot-Marie-Tooth disease axonal type 2X|SPG11-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 450
NM_025137.4(SPG11):c.5866+1G>APathogenic
Hereditary spastic paraplegia 11|not provided|Amyotrophic lateral sclerosis type 5;Charcot-Marie-Tooth disease axonal type 2X;Hereditary spastic paraplegia 11
β˜…β˜…β˜†β˜†2026
NM_025137.4(SPG11):c.5844del (p.Pro1949_Leu1950insTer)Pathogenic
Hereditary spastic paraplegia 11|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2026β†’ Residue 1949
NM_025137.4(SPG11):c.1951C>T (p.Arg651Ter)Pathogenic
Hereditary spastic paraplegia 11|Hereditary spastic paraplegia|not provided|Charcot-Marie-Tooth disease axonal type 2X
β˜…β˜…β˜†β˜†2026β†’ Residue 651
NM_025137.4(SPG11):c.3039-1G>TLikely pathogenic
Hereditary spastic paraplegia 11|Familial cancer of breast
β˜…β˜…β˜†β˜†2026
NM_025137.4(SPG11):c.2317-13C>GPathogenic
Hereditary spastic paraplegia 11|not provided|Amyotrophic lateral sclerosis type 5;Charcot-Marie-Tooth disease axonal type 2X;Hereditary spastic paraplegia 11
β˜…β˜…β˜†β˜†2026
NM_025137.4(SPG11):c.4307_4308del (p.Gln1436fs)Pathogenic
Hereditary spastic paraplegia 11|not provided|Inborn genetic diseases|Charcot-Marie-Tooth disease axonal type 2X|Hereditary spastic paraplegia
β˜…β˜…β˜†β˜†2026β†’ Residue 1436
NM_025137.4(SPG11):c.5470C>T (p.Arg1824Ter)Pathogenic
Hereditary spastic paraplegia 11|not provided|SPG11-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 1824
NM_025137.4(SPG11):c.2716del (p.Gln906fs)Pathogenic
Hereditary spastic paraplegia 11|not provided|Hereditary spastic paraplegia|Amyotrophic lateral sclerosis type 5;Charcot-Marie-Tooth disease axonal type 2X;Hereditary spastic paraplegia 11
β˜…β˜…β˜†β˜†2026β†’ Residue 906
NM_025137.4(SPG11):c.5772_5781dup (p.His1928fs)Pathogenic
not provided|Hereditary spastic paraplegia 11
β˜…β˜…β˜†β˜†2026β†’ Residue 1928
NM_025137.4(SPG11):c.5381T>C (p.Leu1794Pro)Pathogenic
Spastic paraparesis;Difficulty walking;Generalized hyperreflexia;Gait disturbance|Hereditary spastic paraplegia 11|not provided|Hereditary spastic paraplegia|Amyotrophic lateral sclerosis|Inborn genetic diseases|Hereditary spastic paraplegia 11;Charcot-Marie-Tooth disease axonal type 2X;Juvenile amyotrophic lateral sclerosis|Charcot-Marie-Tooth disease axonal type 2X|Amyotrophic lateral sclerosis type 5;Hereditary spastic paraplegia 11;Charcot-Marie-Tooth disease axonal type 2X
β˜…β˜…β˜†β˜†2025β†’ Residue 1794
NM_025137.4(SPG11):c.6739_6742del (p.Glu2247fs)Pathogenic
Hereditary spastic paraplegia 11|not provided|Inborn genetic diseases|Amyotrophic lateral sclerosis type 5;Charcot-Marie-Tooth disease axonal type 2X;Hereditary spastic paraplegia 11
β˜…β˜…β˜†β˜†2025β†’ Residue 2247
NM_025137.4(SPG11):c.6899T>C (p.Leu2300Pro)Pathogenic
Charcot-Marie-Tooth disease axonal type 2X|not provided|Hereditary spastic paraplegia 11
β˜…β˜…β˜†β˜†2025β†’ Residue 2300
View on ClinVar β†—
Related Genes
SPASTProtein interaction99%WASHC5Protein interaction99%AP5S1Protein interaction99%AP5Z1Protein interaction95%PNPLA6Protein interaction95%SPARTProtein interaction95%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
97%
Lung
97%
Ovary
73%
Liver
71%
Brain
70%
Gene Interaction Network
Click a node to explore
SPG11SPASTWASHC5AP5S1AP5Z1PNPLA6SPART
PROTEIN STRUCTURE
Preparing viewer…
PDB8YAB Β· 3.26 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.85LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.76 [0.68–0.85]
RankingsWhere SPG11 stands among ~20K protein-coding genes
  • #4,248of 20,598
    Most Researched112 Β· top quartile
  • #90of 5,498
    Most Pathogenic Variants567 Β· top 5%
  • #7,404of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedSPG11
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia.
PMID: 34983064
Brain Β· 2022
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.90
3
SPG11: clinical and genetic features of seven Czech patients and literature review.
PMID: 35254204
Neurol Res Β· 2022
0.80
4
The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies.
PMID: 24603320
Neuroepidemiology Β· 2014
0.70
5
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
PMID: 34130600
Autophagy Β· 2022
0.60