FSP
MCID: HRD010
MIFTS: 67

Hereditary Spastic Paraplegia (FSP)

Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Hereditary Spastic Paraplegia

MalaCards integrated aliases for Hereditary Spastic Paraplegia:

Name: Hereditary Spastic Paraplegia 12 75 24 53 54 59 37 29 6 15 38 33
Hereditary Spastic Paraparesis 12 24 53 59
Familial Spastic Paraplegia 12 53 59
Strumpell-Lorrain Disease 12 75 59
Spastic Paraplegia, Hereditary 44 72
Hsp 53 59
Spg 53 59
Spastic Paraplegia 3, Autosomal Dominant 72
Spastic Paraplegia Hereditary 55
Spastic Paraplegia, Familial 75
Familial Spastic Paraparesis 53
Strumpell-Lorrain Syndrome 24
French Settlement Disease 12
Strümpell-Lorrain Disease 53
Fsp 53

Characteristics:

Orphanet epidemiological data:

59
hereditary spastic paraplegia
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/100000 (Europe),1-9/100000 (Spain),1-9/100000 (Portugal),1-9/100000 (Worldwide),1-9/100000 (Tunisia),1-9/100000 (Norway),1-9/100000 (Italy),1-9/100000 (Estonia),1-9/100000 (Libyan Arab Jamahiriya); Age of onset: All ages;

Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:2476
KEGG 37 H00266
ICD9CM 35 334.1
MeSH 44 D015419
SNOMED-CT 68 39912006 76043009
ICD10 33 G11.4
ICD10 via Orphanet 34 G11.4
UMLS via Orphanet 73 C0037773 C2931355
Orphanet 59 ORPHA685
UMLS 72 C0037773 C2931355

Summaries for Hereditary Spastic Paraplegia

NINDS : 54 Hereditary spastic paraplegia (HSP), also called familial spastic paraparesis (FSP), refers to a group of inherited disorders that are characterized by progressive weakness and spasticity (stiffness) of the legs. Early in the disease course, there may be mild gait difficulties and stiffness. These symptoms typically slowly progress so that eventually individuals with HSP may require the assistance of a cane, walker, or wheelchair. Though the primary features of "pure" HSP are progressive lower limb spasticity and weakness, complicated forms may be accompanied by other symptoms. These additional symptoms include impaired vision due to cataracts and problems with the optic nerve and retina of the eye, ataxia (lack of muscle coordination), epilepsy, cognitive impairment, peripheral neuropathy, and deafness. The diagnosis of HSP is primarily by neurological examination and testing to rule out other disorders. Brain MRI abnormalities, such as a thin corpus callosum, may be seen in some of the complicated forms of HSP.  Several genetic mutations have been identified which underlie various forms of HSP, and specialized genetic testing and diagnosis are available at some medical centers.  HSP has several forms of inheritance.  Not all children in a family will necessarily develop symptoms, although they may be carriers of the abnormal gene.  Symptoms may begin in childhood or adulthood, depending on the particular HSP gene involved.

MalaCards based summary : Hereditary Spastic Paraplegia, also known as hereditary spastic paraparesis, is related to spastic paraplegia 2, x-linked and spastic paraplegia 20, autosomal recessive, and has symptoms including urgency of micturition, pain in lower limb and leg cramps. An important gene associated with Hereditary Spastic Paraplegia is SPAST (Spastin), and among its related pathways/superpathways are Endocytosis and Lysosome. The drugs Acetylcholine and Cholinergic Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and testes, and related phenotypes are spasticity and gait disturbance

Disease Ontology : 12 A paraplegia that is characterized by progressive stiffness and contraction (spasticity) in the lower limbs.

NIH Rare Diseases : 53 Hereditary spastic paraplegia (HSP) is a group of hereditary, degenerative, neurological disorders that primarily affect the upper motor neurons. Upper motor neurons in the brain and spinal cord deliver signals to the lower motor neurons, which in turn, carry messages to the muscles. In hereditary spastic paraplegia, upper motor neurons slowly degenerate so the muscles do not receive the correct messages, causing progressive spasticity (increased muscle tone/stiffness) and weakness of the legs. This leads to difficulty walking. As degeneration continues, symptoms worsen. If only the lower body is affected, HSP is classified as uncomplicated or pure. HSP is classified as complicated or complex if other systems are involved. In these cases, additional symptoms, including impaired vision, ataxia, epilepsy, cognitive impairment, peripheral neuropathy, and/or deafness, occur. The different forms of HSP are caused by mutations in different genes. Inheritance varies. There are no specific treatments to prevent, slow, or reverse HSP. Individual symptoms may be treated with medications and/or physical therapy.

KEGG : 37
Hereditary spastic paraplegias (SPG) are a group of clinically and genetically diverse disorders characterized by progressive distal limb weakness and lower extremity spasticity.

Wikipedia : 75 Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive... more...

GeneReviews: NBK1509

Related Diseases for Hereditary Spastic Paraplegia

Diseases in the Spastic Paraplegia 3a family:

Spastic Paraplegia 3, Autosomal Dominant Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 17, Autosomal Dominant Spastic Paraplegia 15, Autosomal Recessive
Spastic Paraplegia 23, Autosomal Recessive Spastic Paraplegia 5a, Autosomal Recessive
Spastic Paraplegia 20, Autosomal Recessive Spastic Paraplegia 6, Autosomal Dominant
Spastic Paraplegia 9a, Autosomal Dominant Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 10, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 12, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 13, Autosomal Dominant Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 7, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 25, Autosomal Recessive Spastic Paraplegia 27, Autosomal Recessive
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 29, Autosomal Dominant Spastic Paraplegia 33, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 30, Autosomal Recessive
Spastic Paraplegia 18, Autosomal Recessive Spastic Paraplegia 32, Autosomal Recessive
Spastic Paraplegia 37, Autosomal Dominant Spastic Paraplegia 39, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 38, Autosomal Dominant
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 36, Autosomal Dominant Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 44, Autosomal Recessive Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 51, Autosomal Recessive
Spastic Paraplegia 47, Autosomal Recessive Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 53, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 55, Autosomal Recessive
Spastic Paraplegia 43, Autosomal Recessive Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 72, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 62, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 61, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive
Spastic Paraplegia 73, Autosomal Dominant Spastic Paraplegia 74, Autosomal Recessive
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 75, Autosomal Recessive
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 77, Autosomal Recessive
Spastic Paraplegia 78, Autosomal Recessive Spastic Paraplegia 80, Autosomal Dominant
Hereditary Spastic Paraplegia 23 Hereditary Spastic Paraplegia 51
Hereditary Spastic Paraplegia 72 Hereditary Spastic Paraplegia
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 Spastic Paraplegia 1
Spastic Paraplegia 10 Spastic Paraplegia 12
Spastic Paraplegia 13 Spastic Paraplegia 14
Spastic Paraplegia 15 Spastic Paraplegia 16
Spastic Paraplegia 17 Spastic Paraplegia 18
Spastic Paraplegia 19 Spastic Paraplegia 24
Spastic Paraplegia 25 Spastic Paraplegia 26
Spastic Paraplegia 29 Spastic Paraplegia 3
Spastic Paraplegia 31 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 47
Spastic Paraplegia 51 Spastic Paraplegia 5a
Spastic Paraplegia 5b Spastic Paraplegia 6
Spastic Paraplegia 9 Spastic Paraplegia Type 49
Autosomal Recessive Spastic Paraplegia Type 60 Autosomal Recessive Spastic Paraplegia Type 59
Autosomal Recessive Spastic Paraplegia Type 69 Autosomal Recessive Spastic Paraplegia Type 70
Autosomal Recessive Spastic Paraplegia Type 71 Autosomal Recessive Spastic Paraplegia Type 66
Autosomal Recessive Spastic Paraplegia Type 67 Autosomal Dominant Spastic Paraplegia Type 9b

Diseases related to Hereditary Spastic Paraplegia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 705)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 2, x-linked 35.3 ZFYVE27 REEP1 ATL1
2 spastic paraplegia 20, autosomal recessive 35.1 SPG7 SPART
3 spastic paraplegia 3, autosomal dominant 35.0 ZFYVE27 SPG11 SPAST REEP1 NIPA1 ATL1
4 masa syndrome 35.0 SPG11 SPAST SPART REEP1 NIPA1 ATL1
5 spastic paraplegia 4, autosomal dominant 35.0 ZFYVE27 SPG7 SPG11 SPAST REEP1 NIPA1
6 spastic paraplegia 32, autosomal recessive 35.0 SPG7 SPG11 ATL1
7 spastic paraplegia 15, autosomal recessive 35.0 ZFYVE26 SPG7 SPG11
8 spastic paraplegia 18, autosomal recessive 35.0 WASHC5 REEP1 NIPA1
9 spastic paraplegia 5a, autosomal recessive 35.0 CYP7B1 C19orf12
10 spastic paraplegia 61, autosomal recessive 35.0 SPAST REEP1 ATL1
11 spastic paraplegia 31, autosomal dominant 35.0 ZFYVE27 SPG11 SPAST REEP1 ATL1
12 spastic paraplegia 39, autosomal recessive 35.0 ZFYVE26 WASHC5 REEP1
13 spastic paraplegia 13, autosomal dominant 35.0 WASHC5 SPAST HSPD1 ATL1
14 spastic paraplegia 6, autosomal dominant 35.0 SPAST REEP1 NIPA1 KIF5A ATL1
15 spastic paraplegia 42, autosomal dominant 35.0 WASHC5 REEP1 NIPA1
16 spastic paraplegia 8, autosomal dominant 34.9 WASHC5 SPG11 REEP1 NIPA1 ATL1
17 spastic paraplegia 10, autosomal dominant 34.9 ZFYVE27 SPG11 REEP1 KIF5A ATL1
18 spastic paraplegia 30, autosomal recessive 34.9 WASHC5 REEP1 KIF1A
19 spastic paraplegia 49, autosomal recessive 34.9 ZFYVE26 SPG7 SPG11
20 spastic paraplegia 12, autosomal dominant 34.9 ZFYVE27 SPAST REEP1 KIF5A ATL1
21 spastic paraplegia 24, autosomal recessive 34.9 SPG7 CYP7B1
22 spastic paraplegia 73, autosomal dominant 34.9 SPG7 GBA2 CYP7B1
23 spastic paraplegia 43, autosomal recessive 34.8 CYP7B1 C19orf12
24 spastic paraplegia 57, autosomal recessive 34.8 SPG11 ALS2
25 spastic paraplegia 48, autosomal recessive 34.8 ZFYVE26 SPG11
26 spastic paraplegia 46, autosomal recessive 34.7 SPG11 GBA2
27 spastic paraplegia 76, autosomal recessive 34.7 SPG7 GBA2 CYP7B1
28 spastic paraplegia 33, autosomal dominant 34.7 ZFYVE27 SPAST SPART REEP1
29 spastic paraplegia 47, autosomal recessive 34.6 WASHC5 REEP1
30 spastic paraplegia 7, autosomal recessive 34.6 SPG7 AFG3L2
31 spastic paraplegia 35, autosomal recessive 34.5 ZFYVE26 SPG11
32 spastic paraplegia 5a 34.3 GBA2 CYP7B1
33 spasticity 34.1 WASHC5 SPG7 SPAST KIF1A DDHD1
34 spastic paraplegia 10 34.1 SPAST KIF5A
35 paraplegia 32.8 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG11 SPAST
36 spastic paraparesis 32.7 SPG7 SPG11 SPAST DDHD1
37 lateral sclerosis 32.4 SPG11 KIF5A ALS2
38 primary lateral sclerosis, adult, 1 32.1 SPG7 SPAST ALS2
39 3-methylglutaconic aciduria, type iii 32.1 SPG7 C19orf12 AFG3L2
40 axonal neuropathy 32.0 SPG11 KIF5A C19orf12
41 juvenile amyotrophic lateral sclerosis 31.7 SPG11 C19orf12 ALS2
42 spinocerebellar ataxia 28 30.8 SPG7 AFG3L2
43 hereditary spastic paraplegia 72 12.8
44 hereditary spastic paraplegia 23 12.8
45 hereditary spastic paraplegia 51 12.7
46 pure hereditary spastic paraplegia 12.6
47 complex hereditary spastic paraplegia 12.6
48 pure or complex hereditary spastic paraplegia 12.6
49 ap-4-associated hereditary spastic paraplegia 12.5
50 spastic paraplegia 17, autosomal dominant 12.5

Graphical network of the top 20 diseases related to Hereditary Spastic Paraplegia:



Diseases related to Hereditary Spastic Paraplegia

Symptoms & Phenotypes for Hereditary Spastic Paraplegia

Human phenotypes related to Hereditary Spastic Paraplegia:

59 32 (show all 6)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 59 32 hallmark (90%) Very frequent (99-80%) HP:0001257
2 gait disturbance 59 32 hallmark (90%) Very frequent (99-80%) HP:0001288
3 impaired pain sensation 59 32 hallmark (90%) Very frequent (99-80%) HP:0007328
4 paraplegia 59 32 hallmark (90%) Very frequent (99-80%) HP:0010550
5 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
6 finger syndactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0006101

UMLS symptoms related to Hereditary Spastic Paraplegia:


urgency of micturition, pain in lower limb, leg cramps

GenomeRNAi Phenotypes related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 9.92 AFG3L2 ALS2 ATL1 C19orf12 CYP7B1 DDHD1

MGI Mouse Phenotypes related to Hereditary Spastic Paraplegia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.73 AFG3L2 ALS2 ATL1 HSPD1 KIF1A KIF5A
2 nervous system MP:0003631 9.36 AFG3L2 ALS2 HSPD1 KIF1A KIF5A KY

Drugs & Therapeutics for Hereditary Spastic Paraplegia

Drugs for Hereditary Spastic Paraplegia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 26)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved, Investigational Phase 2, Phase 3 51-84-3 187
2 Cholinergic Agents Phase 2, Phase 3
3 Neurotransmitter Agents Phase 2, Phase 3
4 Acetylcholine Release Inhibitors Phase 2, Phase 3
5 Botulinum Toxins Phase 2, Phase 3
6
Resveratrol Approved, Experimental, Investigational Phase 2 501-36-0 445154
7
chenodeoxycholic acid Approved Phase 2 474-25-9 10133
8
Atorvastatin Approved Phase 2 134523-00-5 60823
9 Analgesics Phase 2
10 Antineoplastic Agents, Phytogenic Phase 2
11 Gastrointestinal Agents Phase 2
12 Cathartics Phase 2
13 Lipid Regulating Agents Phase 2
14 Anti-Inflammatory Agents, Non-Steroidal Phase 2
15 Antioxidants Phase 2
16 Analgesics, Non-Narcotic Phase 2
17 Peripheral Nervous System Agents Phase 2
18 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 2
19 Protective Agents Phase 2
20 Laxatives Phase 2
21 Hypolipidemic Agents Phase 2
22 Anti-Inflammatory Agents Phase 2
23 Platelet Aggregation Inhibitors Phase 2
24 Anticholesteremic Agents Phase 2
25 Antirheumatic Agents Phase 2
26 Antimetabolites Phase 2

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 Botulinum Toxin in Patients With Hereditary Spastic Paraplegia: a Randomized, Double-blind, Placebo-controlled, Crossover Study Completed NCT02604186 Phase 2, Phase 3
2 Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5 Completed NCT02314208 Phase 2 Xenbilox;Tahor
3 Design and Validation of a Modular Physiotherapy Concept for the Treatment of Hereditary Spastic Spinal Paralysis (HSP) - a Randomized Study Completed NCT03961906 Phase 2
4 A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy Completed NCT03627416
5 Studying Cognition in SPG4 Compared to Healthy Controls Completed NCT03104088
6 Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31 Recruiting NCT02859428
7 Phenotype, Genotype & Biomarkers in ALS and Related Disorders Recruiting NCT02327845
8 Studying the Presymptomatic and Early Phase of SPG4 Recruiting NCT03206190
9 Clinical and Molecular Manifestations of Neuromuscular and Neurogenetic Disorders of Childhood Recruiting NCT01568658
10 Studying Non-motor Symptoms in Patients With Hereditary Spastic Paraplegia (HSP) Compared to Healthy Controls Recruiting NCT03204773
11 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
12 A Patient Centric Motor Neuron Disease Activities of Daily Living Scale Enrolling by invitation NCT02852278
13 Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders Not yet recruiting NCT03981276
14 Investigating the Role of SPG20,STK31 Genes in the Carcinogenesis of Colorectal Cancer Not yet recruiting NCT03261752

Search NIH Clinical Center for Hereditary Spastic Paraplegia

Cochrane evidence based reviews: spastic paraplegia, hereditary

Genetic Tests for Hereditary Spastic Paraplegia

Genetic tests related to Hereditary Spastic Paraplegia:

# Genetic test Affiliating Genes
1 Hereditary Spastic Paraplegia 29

Anatomical Context for Hereditary Spastic Paraplegia

MalaCards organs/tissues related to Hereditary Spastic Paraplegia:

41
Brain, Spinal Cord, Testes, Eye, Retina, Cortex, Bone

Publications for Hereditary Spastic Paraplegia

Articles related to Hereditary Spastic Paraplegia:

(show top 50) (show all 1492)
# Title Authors PMID Year
1
A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia. 9 38 4
18200586 2008
2
Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia. 9 38 4
16489470 2006
3
De novo occurrence of novel SPG3A/atlastin mutation presenting as cerebral palsy. 9 38 4
16533974 2006
4
Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation. 9 38 4
15667412 2004
5
SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. 9 38 4
12134148 2002
6
A novel heterozygous variant in ERLIN2 causes autosomal dominant pure hereditary spastic paraplegia. 38 4
29528531 2018
7
Novel homozygous GBA2 mutation in a patient with complicated spastic paraplegia. 38 4
29524657 2018
8
ERLIN1 mutations cause teenage-onset slowly progressive ALS in a large Turkish pedigree. 38 4
29453415 2018
9
ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia. 38 4
28158749 2017
10
NT5C2 novel splicing variant expands the phenotypic spectrum of Spastic Paraplegia (SPG45): case report of a new member of thin corpus callosum SPG-Subgroup. 38 4
28327087 2017
11
ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia. 38 4
27738760 2017
12
Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia. 38 4
26714052 2016
13
Hereditary and metabolic myelopathies. 38 4
27430441 2016
14
Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene. 38 4
26423925 2015
15
Adult-onset autosomal dominant spastic paraplegia linked to a GTPase-effector domain mutation of dynamin 2. 38 4
26517984 2015
16
Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. 38 4
26026163 2015
17
Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia. 38 4
25772097 2015
18
Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. 38 4
25609768 2015
19
A complex form of hereditary spastic paraplegia in three siblings due to somatic mosaicism for a novel SPAST mutation in the mother. 38 4
25315759 2014
20
Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. 38 4
25243380 2014
21
Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. 38 4
25008398 2014
22
Motor protein mutations cause a new form of hereditary spastic paraplegia. 38 4
24808017 2014
23
Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses. 38 4
24451228 2014
24
Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. 38 4
24388663 2014
25
KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction. 38 4
24319291 2014
26
PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. 38 4
24355708 2014
27
Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis. 38 4
24103911 2013
28
Recurrent de novo c.316G>A mutation in NIPA1 hotspot. 38 4
24075313 2013
29
Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12. 38 4
23857908 2013
30
Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. 38 4
23746551 2013
31
Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia. 38 4
23664120 2013
32
Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. 38 4
23176824 2012
33
Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia. 38 4
23176821 2012
34
Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a recessive form of complex hereditary spastic paraplegia. 38 4
23176823 2012
35
Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) . 38 4
22290197 2012
36
Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. 38 4
22232211 2012
37
A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18). 38 4
21796390 2011
38
NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy. 38 4
21599812 2011
39
Expansion of the phenotypic spectrum of SPG6 caused by mutation in NIPA1. 38 4
21419568 2011
40
Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism. 38 4
21381113 2011
41
Hereditary spastic paraplegia-like disorder due to a mitochondrial ATP6 gene point mutation. 38 4
20656066 2011
42
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. 38 4
20613862 2010
43
Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). 38 4
20104589 2010
44
Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence. 38 4
19652142 2009
45
CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. 38 4
19439420 2009
46
New pedigrees and novel mutation expand the phenotype of REEP1-associated hereditary spastic paraplegia (HSP). 38 4
19034539 2009
47
Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. 38 4
19056803 2009
48
Forceps minor region signal abnormality "ears of the lynx": an early MRI finding in spastic paraparesis with thin corpus callosum and mutations in the spatacsin gene (SPG11) on chromosome 15. 38 4
19040626 2009
49
SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia. 38 4
18337587 2008
50
Hereditary spastic paraplegia 3A associated with axonal neuropathy. 38 4
17502470 2007

Variations for Hereditary Spastic Paraplegia

ClinVar genetic disease variations for Hereditary Spastic Paraplegia:

6 (show top 50) (show all 96)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 KIF5A NM_004984.4(KIF5A): c.610C> T (p.Arg204Trp) single nucleotide variant Pathogenic rs1555177629 12:57961297-57961297 12:57567514-57567514
2 KY NM_178554.6(KY): c.51_52insTATCGACATGTGCTGTATCTATCGACAT (p.Val18fs) insertion Pathogenic rs1085307110 3:134369751-134369752 3:134650909-134650910
3 ZFYVE26 NM_015346.4(ZFYVE26): c.6296dup (p.Asn2100fs) duplication Pathogenic rs1555394376 14:68228993-68228993 14:67762276-67762276
4 SPG11 NM_025137.3(SPG11): c.(2244+1_2245-1)_(2620+1_2621-1)del deletion Pathogenic
5 SPG11 NM_025137.4(SPG11): c.733_734del (p.Met245fs) deletion Pathogenic rs312262720 15:44949428-44949429 15:44657230-44657231
6 NIPA1 NM_144599.5(NIPA1): c.316G> A (p.Gly106Arg) single nucleotide variant Pathogenic rs104894490 15:23060816-23060816 15:22812252-22812252
7 CYP7B1 NM_004820.5(CYP7B1): c.825T> A (p.Tyr275Ter) single nucleotide variant Pathogenic rs121908613 8:65528273-65528273 8:64615716-64615716
8 CYP7B1 NM_004820.5(CYP7B1): c.914dup (p.Met305fs) duplication Pathogenic rs1554524697 8:65527726-65527726 8:64615169-64615169
9 SPAST NM_014946.3(SPAST): c.1133T> A (p.Leu378Gln) single nucleotide variant Pathogenic rs1553316816 2:32352051-32352051 2:32126982-32126982
10 SPG7 NM_003119.4(SPG7): c.1447C> T (p.Gln483Ter) single nucleotide variant Pathogenic/Likely pathogenic rs562890289 16:89611178-89611178 16:89544770-89544770
11 C19orf12 NM_001256047.1(C19orf12): c.124G> A (p.Gly42Arg) single nucleotide variant Pathogenic/Likely pathogenic rs200133991 19:30199197-30199197 19:29708290-29708290
12 GBA2 NM_020944.3(GBA2): c.1888C> T (p.Arg630Trp) single nucleotide variant Pathogenic/Likely pathogenic rs398123012 9:35738808-35738808 9:35738811-35738811
13 GBA2 NM_020944.3(GBA2): c.2618G> A (p.Arg873His) single nucleotide variant Pathogenic/Likely pathogenic rs398123015 9:35737332-35737332 9:35737335-35737335
14 KIF1A NM_004321.7(KIF1A): c.206C> T (p.Ser69Leu) single nucleotide variant Pathogenic/Likely pathogenic rs786200949 2:241727625-241727625 2:240788208-240788208
15 SPG7 NM_003119.4(SPG7): c.376G> C (p.Glu126Gln) single nucleotide variant Pathogenic/Likely pathogenic rs912983346 16:89579445-89579445 16:89513037-89513037
16 SPG7 NM_003119.3(SPG7): c.1454_1462delGGCGGGAGA (p.Arg485_Glu487del) deletion Pathogenic/Likely pathogenic rs768823392 16:89613070-89613078 16:89546662-89546670
17 KIF5A NM_004984.4(KIF5A): c.833C> T (p.Pro278Leu) single nucleotide variant Likely pathogenic rs1555177824 12:57963052-57963052 12:57569269-57569269
18 KIF5A NM_004984.4(KIF5A): c.868G> C (p.Asp290His) single nucleotide variant Likely pathogenic rs1555177831 12:57963087-57963087 12:57569304-57569304
19 DDHD2 NM_015214.2(DDHD2): c.1249_1891del deletion Likely pathogenic
20 ERLIN2 NM_007175.8(ERLIN2): c.899A> T (p.Asp300Val) single nucleotide variant Likely pathogenic rs763958615 8:37611512-37611512 8:37753994-37753994
21 REEP1 NM_001164731.2(REEP1): c.25-18176G> C single nucleotide variant Likely pathogenic rs1266102026 2:86509340-86509340 2:86282217-86282217
22 KIF1A NM_004321.7(KIF1A): c.31C> T (p.Arg11Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs548204329 2:241737139-241737139 2:240797722-240797722
23 SACS NM_014363.6(SACS): c.5629C> T (p.Arg1877Ter) single nucleotide variant Conflicting interpretations of pathogenicity rs761089024 13:23912386-23912386 13:23338247-23338247
24 SETX NM_015046.7(SETX): c.3229G> A (p.Asp1077Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs145097270 9:135203756-135203756 9:132328369-132328369
25 NIPA1 NM_144599.5(NIPA1): c.24_26GGC[10] (p.Ala15_Ala16dup) short repeat Conflicting interpretations of pathogenicity rs531550505 15:23086365-23086370 15:22786698-22786703
26 SACS NM_014363.6(SACS): c.13717A> C (p.Asn4573His) single nucleotide variant Conflicting interpretations of pathogenicity rs34382952 13:23904298-23904298 13:23330159-23330159
27 KIF1C NM_006612.6(KIF1C): c.2734C> T (p.Arg912Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs202232792 17:4926868-4926868 17:5023573-5023573
28 SPG7 NM_003119.4(SPG7): c.1529C> T (p.Ala510Val) single nucleotide variant Conflicting interpretations of pathogenicity rs61755320 16:89613145-89613145 16:89546737-89546737
29 SPG11 NM_025137.4(SPG11): c.3818A> G (p.Lys1273Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs76389165 15:44890903-44890903 15:44598705-44598705
30 BICD2 NM_001003800.2(BICD2): c.269A> G (p.Lys90Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs61754130 9:95491490-95491490 9:92729208-92729208
31 SACS NM_014363.6(SACS): c.1373C> T (p.Thr458Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs61729954 13:23929378-23929378 13:23355239-23355239
32 KIF1C NM_006612.6(KIF1C): c.1111G> A (p.Ala371Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs142056835 17:4908241-4908241 17:5004946-5004946
33 KIF1C NM_006612.6(KIF1C): c.2299G> A (p.Gly767Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs118037269 17:4925675-4925675 17:5022380-5022380
34 CYP7B1 NM_004820.5(CYP7B1): c.1456C> T (p.Arg486Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs116171274 8:65509264-65509264 8:64596707-64596707
35 KIF5A NM_004984.4(KIF5A): c.839G> A (p.Arg280His) single nucleotide variant Conflicting interpretations of pathogenicity rs387907288 12:57963058-57963058 12:57569275-57569275
36 MAG NM_080600.2(MAG): c.452C> T (p.Ala151Val) single nucleotide variant Conflicting interpretations of pathogenicity rs144553163 19:35790493-35790493 19:35299590-35299590
37 MAG NM_080600.2(MAG): c.1117A> C (p.Ser373Arg) single nucleotide variant Uncertain significance rs142375870 19:35793497-35793497 19:35302594-35302594
38 MAG NM_080600.2(MAG): c.1646C> T (p.Ser549Leu) single nucleotide variant Uncertain significance rs767886169 19:35802850-35802850 19:35311947-35311947
39 SLC16A2 NM_006517.5(SLC16A2): c.377C> A (p.Ser126Tyr) single nucleotide variant Uncertain significance rs1555979601 X:73641849-73641849 X:74422014-74422014
40 USP8 NM_001128610.3(USP8): c.1084A> G (p.Ile362Val) single nucleotide variant Uncertain significance rs768800460 15:50769562-50769562 15:50477365-50477365
41 USP8 NM_001128610.3(USP8): c.397C> T (p.Arg133Trp) single nucleotide variant Uncertain significance rs202135045 15:50751258-50751258 15:50459061-50459061
42 KIF1C NM_006612.6(KIF1C): c.2591G> A (p.Arg864His) single nucleotide variant Uncertain significance rs146628704 17:4925967-4925967 17:5022672-5022672
43 SPG7 NM_003119.4(SPG7): c.1442C> T (p.Thr481Met) single nucleotide variant Uncertain significance rs376713807 16:89611173-89611173 16:89544765-89544765
44 ZFYVE26 NM_015346.4(ZFYVE26): c.2183G> A (p.Arg728Gln) single nucleotide variant Uncertain significance rs770927853 14:68264796-68264796 14:67798079-67798079
45 SPG11 NM_025137.4(SPG11): c.2486T> G (p.Val829Gly) single nucleotide variant Uncertain significance rs1555455561 15:44914091-44914091 15:44621893-44621893
46 ALS2 NM_020919.4(ALS2): c.3746T> C (p.Phe1249Ser) single nucleotide variant Uncertain significance rs551822626 2:202582890-202582890 2:201718167-201718167
47 AP5B1 NM_138368.5(AP5B1): c.1201C> T (p.Leu401Phe) single nucleotide variant Uncertain significance rs201041158 11:65546763-65546763 11:65779292-65779292
48 MARS1 NM_004990.4(MARS1): c.-18C> T single nucleotide variant Uncertain significance rs201535531 12:57881856-57881856 12:57488073-57488073
49 KIF5A NM_004984.4(KIF5A): c.572G> A (p.Arg191His) single nucleotide variant Uncertain significance rs1488871976 12:57960979-57960979 12:57567196-57567196
50 ALS2 NM_020919.4(ALS2): c.3206G> A (p.Gly1069Glu) single nucleotide variant Uncertain significance rs200706696 2:202591249-202591249 2:201726526-201726526

Copy number variations for Hereditary Spastic Paraplegia from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 144964 2 32142183 32236210 Deletion SPAST hereditary spastic paraplegia

Expression for Hereditary Spastic Paraplegia

Search GEO for disease gene expression data for Hereditary Spastic Paraplegia.

Pathways for Hereditary Spastic Paraplegia

Pathways related to Hereditary Spastic Paraplegia according to KEGG:

37
# Name Kegg Source Accession
1 Endocytosis hsa04144
2 Lysosome hsa04142

Pathways related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.31 ZFYVE27 WASHC5 SPART KIF5A

GO Terms for Hereditary Spastic Paraplegia

Cellular components related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 9.88 ZFYVE27 SPAST REEP1 GBA2 CYP7B1 ATL1
2 endoplasmic reticulum GO:0005783 9.86 ZFYVE27 WASHC5 SPAST REEP1 GBA2 CYP7B1
3 neuron projection GO:0043005 9.8 WASHC5 KIF5A KIF1A ALS2
4 neuronal cell body GO:0043025 9.78 WASHC5 KIF5A KIF1A ALS2
5 axon GO:0030424 9.72 ZFYVE27 SPG11 KIF1A ATL1 ALS2
6 early endosome GO:0005769 9.67 WASHC5 NIPA1 HSPD1 ALS2
7 midbody GO:0030496 9.63 ZFYVE26 SPAST SPART
8 m-AAA complex GO:0005745 9.16 SPG7 AFG3L2
9 endoplasmic reticulum tubular network GO:0071782 9.13 ZFYVE27 REEP1 ATL1
10 axon cytoplasm GO:1904115 8.92 SPG7 SPAST KIF5A KIF1A
11 cytoplasm GO:0005737 10.25 ZFYVE27 ZFYVE26 WASHC5 SPG11 SPAST SPART

Biological processes related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion organization GO:0007005 9.43 SPG7 HSPD1 AFG3L2
2 mitochondrial calcium ion transmembrane transport GO:0006851 9.4 SPG7 AFG3L2
3 synaptic vesicle transport GO:0048489 9.37 SPG11 KIF5A
4 mitochondrial calcium ion homeostasis GO:0051560 9.32 C19orf12 AFG3L2
5 retrograde neuronal dense core vesicle transport GO:1990049 9.16 KIF5A KIF1A
6 anterograde axonal transport GO:0008089 9.13 SPG7 SPAST KIF1A
7 axonogenesis GO:0007409 8.92 SPAST ATL1 ALS2 AFG3L2

Molecular functions related to Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase activity GO:0016887 9.46 SPAST KIF5A KIF1A HSPD1
2 unfolded protein binding GO:0051082 9.43 SPG7 HSPD1 AFG3L2
3 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 9.32 KIF5A KIF1A
4 microtubule binding GO:0008017 9.26 SPAST REEP1 KIF5A KIF1A
5 hydrolase activity GO:0016787 9.1 SPG7 KY GBA2 DDHD1 ATL1 AFG3L2

Sources for Hereditary Spastic Paraplegia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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