SPG11

SPG11 vesicle trafficking associated, spatacsin

Basic information

Region (hg38): 15:44554818-44663688

Previous symbols: [ "KIAA1840", "ALS5" ]

Links

ENSG00000104133NCBI:80208OMIM:610844HGNC:11226Uniprot:Q96JI7AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • hereditary spastic paraplegia 11 (Definitive), mode of inheritance: AR
  • hereditary spastic paraplegia 11 (Strong), mode of inheritance: AR
  • Charcot-Marie-Tooth disease axonal type 2X (Strong), mode of inheritance: AR
  • amyotrophic lateral sclerosis type 5 (Strong), mode of inheritance: AR
  • hereditary spastic paraplegia 11 (Definitive), mode of inheritance: AR
  • hereditary spastic paraplegia 11 (Supportive), mode of inheritance: AR
  • juvenile amyotrophic lateral sclerosis (Supportive), mode of inheritance: AR
  • Charcot-Marie-Tooth disease axonal type 2X (Supportive), mode of inheritance: AR
  • amyotrophic lateral sclerosis type 5 (Strong), mode of inheritance: AR
  • Charcot-Marie-Tooth disease axonal type 2X (Strong), mode of inheritance: AR
  • hereditary spastic paraplegia 11 (Strong), mode of inheritance: AR
  • hereditary spastic paraplegia 11 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Amyotrophic lateral sclerosis 5, juvenile recessive; Charcot-Marie-Tooth disease, axonal, type 2X; Spastic paraplegia 11, autosomal recessiveARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic17717710; 18067136; 17322883; 18663179; 18787847; 19196735; 19194956; 19513778; 20108361; 20110243; 20301389; 20390432; 20571989; 20971220; 21035867; 21381113; 21625935; 22154821; 22175763; 23043354; 23121729; 26556829

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPG11 gene.

  • Hereditary_spastic_paraplegia_11 (3077 variants)
  • not_provided (601 variants)
  • Inborn_genetic_diseases (571 variants)
  • Amyotrophic_lateral_sclerosis_type_5 (315 variants)
  • Charcot-Marie-Tooth_disease_axonal_type_2X (313 variants)
  • Hereditary_spastic_paraplegia (150 variants)
  • not_specified (105 variants)
  • SPG11-related_disorder (58 variants)
  • Amyotrophic_lateral_sclerosis (10 variants)
  • Juvenile_amyotrophic_lateral_sclerosis (5 variants)
  • Abnormal_central_motor_function (5 variants)
  • Spastic_Paraplegia,_Recessive (4 variants)
  • See_cases (4 variants)
  • Intellectual_disability (3 variants)
  • Spastic_paraplegia (2 variants)
  • Spastic_paraparesis (2 variants)
  • Metabolic_disease (2 variants)
  • SPG11-related_spastic_paraplegia (2 variants)
  • Gait_disturbance (2 variants)
  • Neurofibromatosis,_type_1 (2 variants)
  • Difficulty_walking (2 variants)
  • Generalized_hyperreflexia (2 variants)
  • Autism_spectrum_disorder (1 variants)
  • Early-onset_Parkinson_disease_20 (1 variants)
  • Charcot-Marie-Tooth_disease (1 variants)
  • Abnormal_brain_morphology (1 variants)
  • Cerebral_amyloid_angiopathy,_APP-related (1 variants)
  • Spastic_ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPG11 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025137.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
26
clinvar
820
clinvar
5
clinvar
853
missense
7
clinvar
10
clinvar
1318
clinvar
63
clinvar
7
clinvar
1405
nonsense
110
clinvar
42
clinvar
12
clinvar
164
start loss
1
1
frameshift
217
clinvar
75
clinvar
27
clinvar
319
splice donor/acceptor (+/-2bp)
21
clinvar
60
clinvar
1
clinvar
82
Total 355 189 1385 883 12

Highest pathogenic variant AF is 0.00017781225

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SPG11protein_codingprotein_codingENST00000261866 40100983
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.60e-390.94712536703811257480.00152
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.3913601.22e+31.110.000060916162
Missense in Polyphen429412.91.0395520
Synonymous-2.175214621.130.00002284514
Loss of Function3.30811200.6750.000005841505

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002640.00258
Ashkenazi Jewish0.0009930.000993
East Asian0.001580.00158
Finnish0.0006470.000647
European (Non-Finnish)0.001860.00186
Middle Eastern0.001580.00158
South Asian0.001510.00150
Other0.001140.00114

dbNSFP

Source: dbNSFP

Function
FUNCTION: May play a role in neurite plasticity by maintaining cytoskeleton stability and regulating synaptic vesicle transport. {ECO:0000269|PubMed:24794856}.;
Disease
DISEASE: Amyotrophic lateral sclerosis 5, juvenile (ALS5) [MIM:602099]: A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. ALS5 is an autosomal recessive, juvenile form characterized by onset of upper and lower motor neuron signs before age 25. {ECO:0000269|PubMed:20110243}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease 2X (CMT2X) [MIM:616668]: An autosomal recessive, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2X patients manifest a slowly progressive, peripheral neuropathy affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Some patients also have upper limb involvement. {ECO:0000269|PubMed:26556829}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.113

Intolerance Scores

loftool
0.615
rvis_EVS
-0.48
rvis_percentile_EVS
22.79

Haploinsufficiency Scores

pHI
0.483
hipred
N
hipred_score
0.414
ghis
0.542

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.414

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Spg11
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name
spg11
Affected structure
retinal ganglion cell
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
chemical synaptic transmission;axo-dendritic transport;synaptic vesicle transport;axon extension;phagosome-lysosome fusion involved in apoptotic cell clearance;walking behavior
Cellular component
nucleolus;cytoplasm;lysosomal membrane;cytosol;plasma membrane;axon;dendrite;cytoplasmic vesicle;synapse
Molecular function
protein binding