SPG11
Basic information
Region (hg38): 15:44554818-44663688
Previous symbols: [ "KIAA1840", "ALS5" ]
Links
Phenotypes
GenCC
Source:
- 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:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Amyotrophic lateral sclerosis 5, juvenile recessive; Charcot-Marie-Tooth disease, axonal, type 2X; Spastic paraplegia 11, autosomal recessive | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 17717710; 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
- 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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 26 | 820 | 853 | |||
missense | 10 | 1318 | 63 | 1405 | ||
nonsense | 110 | 42 | 12 | 164 | ||
start loss | 1 | 1 | ||||
frameshift | 217 | 75 | 27 | 319 | ||
splice donor/acceptor (+/-2bp) | 21 | 60 | 82 | |||
Total | 355 | 189 | 1385 | 883 | 12 |
Highest pathogenic variant AF is 0.00017781225
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
SPG11 | protein_coding | protein_coding | ENST00000261866 | 40 | 100983 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.60e-39 | 0.947 | 125367 | 0 | 381 | 125748 | 0.00152 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -1.39 | 1360 | 1.22e+3 | 1.11 | 0.0000609 | 16162 |
Missense in Polyphen | 429 | 412.9 | 1.039 | 5520 | ||
Synonymous | -2.17 | 521 | 462 | 1.13 | 0.0000228 | 4514 |
Loss of Function | 3.30 | 81 | 120 | 0.675 | 0.00000584 | 1505 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00264 | 0.00258 |
Ashkenazi Jewish | 0.000993 | 0.000993 |
East Asian | 0.00158 | 0.00158 |
Finnish | 0.000647 | 0.000647 |
European (Non-Finnish) | 0.00186 | 0.00186 |
Middle Eastern | 0.00158 | 0.00158 |
South Asian | 0.00151 | 0.00150 |
Other | 0.00114 | 0.00114 |
dbNSFP
Source:
- 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
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | High | High | High |
Primary Immunodeficiency | High | High | High |
Cancer | High | High | High |
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