FSP
MCID: HRD010
MIFTS: 66

Hereditary Spastic Paraplegia (FSP)

Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle 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 74 25 20 53 58 36 29 6 15 37 32
Hereditary Spastic Paraparesis 12 25 20 58
Familial Spastic Paraplegia 12 20 58
Strumpell-Lorrain Disease 12 74 58
Spastic Paraplegia, Hereditary 44 71
Hsp 20 58
Spg 20 58
Spastic Paraplegia 3, Autosomal Dominant 71
Spastic Paraplegia Hereditary 54
Spastic Paraplegia, Familial 74
Familial Spastic Paraparesis 20
Strumpell-Lorrain Syndrome 25
French Settlement Disease 12
Strümpell-Lorrain Disease 20
Fsp 20

Characteristics:

Orphanet epidemiological data:

58
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: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:2476
KEGG 36 H00266
ICD9CM 34 334.1
MeSH 44 D015419
NCIt 50 C140267
SNOMED-CT 67 267692008
ICD10 32 G11.4
ICD10 via Orphanet 33 G11.4
UMLS via Orphanet 72 C0037773 C2931355
Orphanet 58 ORPHA685
UMLS 71 C0037773 C2931355

Summaries for Hereditary Spastic Paraplegia

NINDS : 53 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 4, autosomal dominant, and has symptoms including urgency of micturition, pain in lower limb and leg cramps. An important gene associated with Hereditary Spastic Paraplegia is KIF5A (Kinesin Family Member 5A), and among its related pathways/superpathways are Endocytosis and Lysosome. The drugs Acetylcholine and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include spinal cord, eye and retina, 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.

GARD : 20 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 : 36 Hereditary spastic paraplegias (SPG) are a group of clinically and genetically diverse disorders characterized by progressive distal limb weakness and lower extremity spasticity.

Wikipedia : 74 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 Dominant
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
Spastic Paraplegia 81, Autosomal Recessive Spastic Paraplegia 82, Autosomal Recessive
Spastic Paraplegia 83, Autosomal Recessive Hereditary Spastic Paraplegia 23
Hereditary Spastic Paraplegia 30 Hereditary Spastic Paraplegia 51
Hereditary Spastic Paraplegia 72 Hereditary Spastic Paraplegia
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 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 32
Spastic Paraplegia 39 Spastic Paraplegia 47
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 790)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 2, x-linked 34.0 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
2 spastic paraplegia 4, autosomal dominant 33.9 ZFYVE26 WASHC5 SPG7 SPG11 SPAST SACS
3 spastic paraplegia 15, autosomal recessive 33.9 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
4 masa syndrome 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
5 spastic paraplegia 10, autosomal dominant 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
6 spastic paraplegia 31, autosomal dominant 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
7 spastic paraplegia 6, autosomal dominant 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
8 spastic paraplegia 8, autosomal dominant 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
9 spastic paraplegia 39, autosomal recessive 33.8 ZFYVE26 WASHC5 SPG7 SPG11 SPAST GBA2
10 spastic paraplegia 18, autosomal recessive 33.8 ZFYVE26 WASHC5 SPG7 SPG11 REEP1 NIPA1
11 spastic paraplegia 20, autosomal recessive 33.7 ZFYVE26 SPG7 SPAST NIPA1 ATL1
12 spastic paraplegia 12, autosomal dominant 33.7 ZFYVE26 WASHC5 SPG11 SPAST REEP1 NIPA1
13 spastic paraplegia 3, autosomal dominant 33.7 SPG7 SPG11 SPAST REEP1 NIPA1 ATL1
14 spastic paraplegia 13, autosomal dominant 33.7 SPG7 SPG11 SPAST REEP1 NIPA1 KIF5A
15 spastic paraplegia 5a, autosomal recessive 33.7 ZFYVE26 SPG7 SPG11 SPAST KIF5A CYP7B1
16 spastic paraplegia 42, autosomal dominant 33.6 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
17 hereditary spastic paraplegia 30 33.6 WASHC5 SPG7 SPG11 SPAST REEP1 KIF5A
18 spastic paraplegia 17, autosomal dominant 33.6 ZFYVE26 WASHC5 SPG11 SPAST REEP1 NIPA1
19 spastic paraplegia 48, autosomal recessive 33.6 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
20 spastic paraplegia 11, autosomal recessive 33.6 ZFYVE26 SPG7 SPG11 SPAST
21 spastic paraplegia 35, autosomal recessive 33.6 ZFYVE26 WASHC5 SPG7 SPG11 REEP1 FA2H
22 spastic paraplegia 7, autosomal recessive 33.6 SPG7 SPG11
23 paraplegia 33.6 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
24 spastic paraplegia 26, autosomal recessive 33.6 SPG7 SPG11 REEP1 GBA2 FA2H
25 spastic paraplegia 46, autosomal recessive 33.6 ZFYVE26 SPG7 SPG11 SPAST GBA2 FA2H
26 spastic paraplegia 47, autosomal recessive 33.6 ZFYVE26 WASHC5 SPG7 SPG11 SPAST REEP1
27 hereditary spastic paraplegia 72 33.5 ZFYVE26 SPG7 SPG11 SPAST REEP1 ERLIN2
28 spastic paraplegia 33, autosomal dominant 33.5 ZFYVE26 WASHC5 SPG11 SPAST REEP1 NIPA1
29 hereditary spastic paraplegia 23 33.5 ZFYVE26 WASHC5 SPG11 CYP7B1
30 spastic paraplegia 43, autosomal recessive 33.5 SPG11 SPAST GBA2 FA2H ERLIN2 C19orf12
31 spastic paraplegia 56, autosomal recessive 33.5 ZFYVE26 SPG7 SPG11 GBA2 FA2H DDHD2
32 spastic paraplegia 54, autosomal recessive 33.5 SPG7 SPG11 REEP1 GBA2 FA2H DDHD2
33 spastic paraplegia 61, autosomal recessive 33.5 ZFYVE26 SPG11 SPAST REEP1 ATL1
34 spastic paraplegia 57, autosomal recessive 33.4 SPG11 SACS REEP1 KIF5A KIF1A ERLIN2
35 spastic paraplegia 28, autosomal recessive 33.4 SPG7 SPG11 REEP1 FA2H DDHD2
36 spastic paraplegia 73, autosomal dominant 33.4 REEP1 GBA2 FA2H DDHD2 ATL1
37 spastic paraplegia 14, autosomal recessive 33.4 SPG7 SPG11 SPAST ATL1
38 spastic paraplegia 37, autosomal dominant 33.4 ZFYVE26 WASHC5 REEP1 ERLIN2
39 spastic paraplegia 16, x-linked 33.4 WASHC5 SPG7 SPG11 SPAST
40 spastic paraplegia 49, autosomal recessive 33.4 ZFYVE26 SPG7 SPG11 DDHD2
41 spastic paraplegia 34, x-linked 33.4 ZFYVE26 WASHC5 REEP1
42 spastic paraplegia 32, autosomal recessive 33.4 WASHC5 SPG7 SPG11
43 spastic paraplegia 25, autosomal recessive 33.3 ZFYVE26 WASHC5 REEP1
44 hereditary spastic paraplegia 51 33.3 ZFYVE26 SPG7 SPG11
45 spastic paraplegia 50, autosomal recessive 33.3 ZFYVE26 SPG7 SPG11
46 spastic paraplegia 44, autosomal recessive 33.3 SPG11 ERLIN2 CYP7B1
47 spastic paraplegia 63, autosomal recessive 33.3 SPG7 SPG11 CYP7B1
48 spastic paraplegia 55, autosomal recessive 33.3 ZFYVE26 SPG7 SPG11
49 spastic paraplegia 64, autosomal recessive 33.3 SPG7 SPG11 SPAST
50 spastic paraplegia 29, autosomal dominant 33.3 ZFYVE26 WASHC5

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:

58 31 (show all 6)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
2 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
3 impaired pain sensation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007328
4 paraplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0010550
5 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
6 finger syndactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0006101

UMLS symptoms related to Hereditary Spastic Paraplegia:


urgency of micturition, pain in lower limb, leg cramps

MGI Mouse Phenotypes related to Hereditary Spastic Paraplegia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.77 ATL1 DDHD2 EPHB1 FA2H KIF1A KIF5A
2 nervous system MP:0003631 9.4 DDHD2 EPHB1 FA2H KIF1A KIF5A REEP1

Drugs & Therapeutics for Hereditary Spastic Paraplegia

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

(show all 29)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved, Investigational Phase 2, Phase 3 51-84-3 187
2 Neurotransmitter Agents Phase 2, Phase 3
3 Cholinergic Agents Phase 2, Phase 3
4 Botulinum Toxins Phase 2, Phase 3
5
Atorvastatin Approved Phase 2 134523-00-5 60823
6
chenodeoxycholic acid Approved Phase 2 474-25-9 10133
7
Evolocumab Approved Phase 1, Phase 2 1256937-27-5
8
Resveratrol Investigational Phase 2 501-36-0 445154
9 Protective Agents Phase 2
10 Anti-Inflammatory Agents Phase 2
11 Cathartics Phase 2
12 Antioxidants Phase 2
13 Gastrointestinal Agents Phase 2
14 Analgesics, Non-Narcotic Phase 2
15 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 2
16 Anti-Inflammatory Agents, Non-Steroidal Phase 2
17 Platelet Aggregation Inhibitors Phase 2
18 Antirheumatic Agents Phase 2
19 Analgesics Phase 2
20 Laxatives Phase 2
21 Antimetabolites Phase 1, Phase 2
22 Hypolipidemic Agents Phase 1, Phase 2
23 Lipid Regulating Agents Phase 1, Phase 2
24 Anticholesteremic Agents Phase 1, Phase 2
25
Idebenone Approved, Investigational 58186-27-9
26
Aspartic acid Approved, Nutraceutical 56-84-8 5960
27
Creatine Approved, Investigational, Nutraceutical 57-00-1 586
28
Choline Approved, Nutraceutical 62-49-7 305
29 N-Methylaspartate

Interventional clinical trials:

(show all 17)
# 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 Design and Validation of a Modular Physiotherapy Concept for the Treatment of Hereditary Spastic Spinal Paralysis (HSP) - a Randomized Study Completed NCT03961906 Phase 2
3 Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5 Completed NCT02314208 Phase 2 Xenbilox;Tahor
4 PCSK9 Inhibitor Treatment for Patients With Hereditary Spastic Paraplegia Type 5 Recruiting NCT04101643 Phase 1, Phase 2 evolocumab
5 A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Improvement of Gait in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy Completed NCT03627416
6 Nuclear Magnetic Spectroscopy for the Evaluation of Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis Completed NCT00023075
7 A Patient Centric Motor Neuron Disease Activities of Daily Living Scale Completed NCT02852278
8 Studying Cognition in SPG4 Compared to Healthy Controls Completed NCT03104088
9 Studying Non-motor Symptoms in Patients With Hereditary Spastic Paraplegia (HSP) Compared to Healthy Controls Completed NCT03204773
10 Improving Gait Adaptability in Hereditary Spastic Paraplegia During Task-specific Training on the C-Mill: Towards Evidence-Based and Individually Tailored Rehabilitation Recruiting NCT04180098
11 Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders Recruiting NCT03981276
12 Studying the Presymptomatic and Early Phase of SPG4 Recruiting NCT03206190
13 Registry and Natural History Study for AP-4 Associated Hereditary Spastic Paraplegia (AP-4-HSP) Recruiting NCT04712812
14 Clinical and Molecular Manifestations of Neuromuscular and Neurogenetic Disorders of Childhood Recruiting NCT01568658
15 Phenotype, Genotype & Biomarkers in ALS and Related Disorders Recruiting NCT02327845
16 SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP) Recruiting NCT04256681
17 Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31 Terminated NCT02859428

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:

40
Spinal Cord, Eye, Retina, Brain, Cortex, Cerebellum, Skeletal Muscle

Publications for Hereditary Spastic Paraplegia

Articles related to Hereditary Spastic Paraplegia:

(show top 50) (show all 1694)
# Title Authors PMID Year
1
A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia. 25 61 54
18200586 2008
2
De novo occurrence of novel SPG3A/atlastin mutation presenting as cerebral palsy. 54 25 61
16533974 2006
3
Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia. 25 54 61
16489470 2006
4
Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation. 54 25 61
15667412 2004
5
SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. 61 54 25
12134148 2002
6
A novel heterozygous variant in ERLIN2 causes autosomal dominant pure hereditary spastic paraplegia. 61 25
29528531 2018
7
ERLIN1 mutations cause teenage-onset slowly progressive ALS in a large Turkish pedigree. 61 25
29453415 2018
8
Novel homozygous GBA2 mutation in a patient with complicated spastic paraplegia. 61 25
29524657 2018
9
ATPase-deficient mitochondrial inner membrane protein ATAD3A disturbs mitochondrial dynamics in dominant hereditary spastic paraplegia. 61 25
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. 61 25
28327087 2017
11
ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia. 61 25
27738760 2017
12
Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia. 61 25
26714052 2016
13
Hereditary and metabolic myelopathies. 25 61
27430441 2016
14
Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene. 25 61
26423925 2015
15
Adult-onset autosomal dominant spastic paraplegia linked to a GTPase-effector domain mutation of dynamin 2. 61 25
26517984 2015
16
Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. 61 25
26026163 2015
17
Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia. 61 25
25772097 2015
18
Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. 25 61
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. 61 25
25315759 2014
20
Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. 25 61
25243380 2014
21
Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. 25 61
25008398 2014
22
Motor protein mutations cause a new form of hereditary spastic paraplegia. 61 25
24808017 2014
23
Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses. 61 25
24451228 2014
24
Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. 25 61
24388663 2014
25
KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction. 61 25
24319291 2014
26
PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. 25 61
24355708 2014
27
Recurrent de novo c.316G>A mutation in NIPA1 hotspot. 25 61
24075313 2013
28
Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis. 61 25
24103911 2013
29
Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12. 25 61
23857908 2013
30
Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. 61 25
23746551 2013
31
Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia. 25 61
23664120 2013
32
Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. 25 61
23176824 2012
33
Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia. 61 25
23176821 2012
34
Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a recessive form of complex hereditary spastic paraplegia. 61 25
23176823 2012
35
Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) . 25 61
22290197 2012
36
Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. 25 61
22232211 2012
37
A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18). 25 61
21796390 2011
38
NIPA1 mutation in complex hereditary spastic paraplegia with epilepsy. 61 25
21599812 2011
39
Expansion of the phenotypic spectrum of SPG6 caused by mutation in NIPA1. 25 61
21419568 2011
40
Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism. 61 25
21381113 2011
41
Hereditary spastic paraplegia-like disorder due to a mitochondrial ATP6 gene point mutation. 61 25
20656066 2011
42
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. 61 25
20613862 2010
43
Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). 25 61
20104589 2010
44
Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence. 25 61
19652142 2009
45
CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. 61 25
19439420 2009
46
New pedigrees and novel mutation expand the phenotype of REEP1-associated hereditary spastic paraplegia (HSP). 25 61
19034539 2009
47
Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. 25 61
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. 25 61
19040626 2009
49
SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia. 25 61
18337587 2008
50
Hereditary spastic paraplegia 3A associated with axonal neuropathy. 61 25
17502470 2007

Variations for Hereditary Spastic Paraplegia

ClinVar genetic disease variations for Hereditary Spastic Paraplegia:

6 (show top 50) (show all 121)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KIF26A NM_015656.1(KIF26A):c.1381del (p.Ala461fs) Deletion association 428591 rs1555389474 14:104638963-104638963 14:104172626-104172626
2 SPG7 NM_003119.4(SPG7):c.771_772TG[1] (p.Val258fs) Microsatellite Pathogenic 504920 rs768136171 16:89595899-89595900 16:89529489-89529490
3 KIF5A NM_004984.4(KIF5A):c.610C>T (p.Arg204Trp) SNV Pathogenic 424651 rs1555177629 12:57961297-57961297 12:57567514-57567514
4 SPG7 NM_003119.3(SPG7):c.1454_1462delGGCGGGAGA (p.Arg485_Glu487del) Deletion Pathogenic 411680 rs768823392 16:89613065-89613073 16:89546657-89546665
5 CYP7B1 NM_004820.5(CYP7B1):c.1456C>T (p.Arg486Cys) SNV Pathogenic 6107 rs116171274 8:65509264-65509264 8:64596707-64596707
6 ZFYVE26 NM_015346.4(ZFYVE26):c.6296dup (p.Asn2100fs) Duplication Pathogenic 424650 rs1555394376 14:68228992-68228993 14:67762275-67762276
7 SPAST NM_014946.3(SPAST):c.1133T>A (p.Leu378Gln) SNV Pathogenic 424653 rs1553316816 2:32352051-32352051 2:32126982-32126982
8 NIPA1 NM_144599.5(NIPA1):c.316G>A (p.Gly106Arg) SNV Pathogenic 2523 rs104894490 15:23060816-23060816 15:22812252-22812252
9 SPG11 NM_025137.3(SPG11):c.(2244+1_2245-1)_(2620+1_2621-1)del Deletion Pathogenic 424655
10 C19orf12 NM_001031726.3(C19orf12):c.157G>A (p.Gly53Arg) SNV Pathogenic 183298 rs200133991 19:30199197-30199197 19:29708290-29708290
11 KIF1A NM_004321.7(KIF1A):c.206C>T (p.Ser69Leu) SNV Pathogenic 188057 rs786200949 2:241727625-241727625 2:240788208-240788208
12 EPHB1 NM_178554.6(KY):c.51_52insTATCGACATGTGCTGTATCTATCGACAT (p.Val18fs) Insertion Pathogenic 402246 rs1085307110 3:134369751-134369752 3:134650909-134650910
13 SPG7 NM_003119.4(SPG7):c.1447C>T (p.Gln483Ter) SNV Pathogenic 390378 rs562890289 16:89611178-89611178 16:89544770-89544770
14 GBA2 NM_020944.3(GBA2):c.2618G>A (p.Arg873His) SNV Pathogenic 41490 rs398123015 9:35737332-35737332 9:35737335-35737335
15 CYP7B1 NM_004820.5(CYP7B1):c.914dup (p.Met305fs) Duplication Pathogenic 424649 rs1554524697 8:65527725-65527726 8:64615168-64615169
16 KIF1A NM_004321.7(KIF1A):c.31C>T (p.Arg11Trp) SNV Pathogenic 424652 rs548204329 2:241737139-241737139 2:240797722-240797722
17 KIF5A NM_004984.4(KIF5A):c.839G>A (p.Arg280His) SNV Pathogenic 37130 rs387907288 12:57963058-57963058 12:57569275-57569275
18 SPG11 NM_025137.4(SPG11):c.733_734del (p.Met245fs) Deletion Pathogenic 1112 rs312262720 15:44949428-44949429 15:44657230-44657231
19 SPG7 NM_003119.4(SPG7):c.376G>C (p.Glu126Gln) SNV Pathogenic 424654 rs912983346 16:89579445-89579445 16:89513037-89513037
20 GBA2 NM_020944.3(GBA2):c.1888C>T (p.Arg630Trp) SNV Pathogenic 41485 rs398123012 9:35738808-35738808 9:35738811-35738811
21 CYP7B1 NM_004820.5(CYP7B1):c.825T>A (p.Tyr275Ter) SNV Pathogenic 6105 rs121908613 8:65528273-65528273 8:64615716-64615716
22 SPG11 NM_025137.4(SPG11):c.3711dup (p.Tyr1238fs) Duplication Pathogenic 466523 rs750663981 15:44891009-44891010 15:44598811-44598812
23 SPG7 NM_003119.4(SPG7):c.1053dup (p.Gly352fs) Duplication Pathogenic 411675 rs760818649 16:89598370-89598371 16:89531962-89531963
24 SPG7 NM_003119.4(SPG7):c.1529C>T (p.Ala510Val) SNV Pathogenic/Likely pathogenic 42016 rs61755320 16:89613145-89613145 16:89546737-89546737
25 SH3TC2 NM_024577.3(SH3TC2):c.1402_1403delinsTT (p.Ala468Phe) Indel Likely pathogenic 216737 rs863224780 5:148407892-148407893 5:149028329-149028330
26 PLEKHG5 NM_020631.6(PLEKHG5):c.773C>T (p.Pro258Leu) SNV Likely pathogenic 827645 rs910474236 1:6533333-6533333 1:6473273-6473273
27 FA2H NM_024306.5(FA2H):c.620C>T (p.Thr207Met) SNV Likely pathogenic 930104 16:74753052-74753052 16:74719154-74719154
28 DDHD2 NM_015214.2(DDHD2):c.1249_1891del Deletion Likely pathogenic 183317
29 SACS NM_014363.6(SACS):c.1640C>T (p.Pro547Leu) SNV Likely pathogenic 424657 rs140507581 13:23929111-23929111 13:23354972-23354972
30 KIF5A NM_004984.4(KIF5A):c.868G>C (p.Asp290His) SNV Likely pathogenic 424659 rs1555177831 12:57963087-57963087 12:57569304-57569304
31 ERLIN2 NM_007175.8(ERLIN2):c.899A>T (p.Asp300Val) SNV Likely pathogenic 424656 rs763958615 8:37611512-37611512 8:37753994-37753994
32 KIF5A NM_004984.4(KIF5A):c.833C>T (p.Pro278Leu) SNV Likely pathogenic 424658 rs1555177824 12:57963052-57963052 12:57569269-57569269
33 REEP1 NM_001371279.1(REEP1):c.58G>C (p.Ala20Pro) SNV Likely pathogenic 424660 rs1266102026 2:86509340-86509340 2:86282217-86282217
34 MAG NM_002361.4(MAG):c.1117A>C (p.Ser373Arg) SNV Uncertain significance 424677 rs142375870 19:35793497-35793497 19:35302594-35302594
35 SPG11 NM_025137.4(SPG11):c.2486T>G (p.Val829Gly) SNV Uncertain significance 424696 rs1555455561 15:44914091-44914091 15:44621893-44621893
36 KIF1C NM_006612.6(KIF1C):c.2299G>A (p.Gly767Arg) SNV Uncertain significance 424674 rs118037269 17:4925675-4925675 17:5022380-5022380
37 BICD2 NM_001003800.2(BICD2):c.761A>G (p.Lys254Arg) SNV Uncertain significance 424684 rs1367809298 9:95482883-95482883 9:92720601-92720601
38 AP5B1 NM_138368.5(AP5B1):c.2089T>C (p.Phe697Leu) SNV Uncertain significance 424669 rs1555023306 11:65545875-65545875 11:65778404-65778404
39 BSCL2 NM_032667.6(BSCL2):c.617G>T (p.Arg206Leu) SNV Uncertain significance 424667 rs763884653 11:62459902-62459902 11:62692430-62692430
40 KIF1C NM_006612.6(KIF1C):c.2734C>T (p.Arg912Trp) SNV Uncertain significance 209167 rs202232792 17:4926868-4926868 17:5023573-5023573
41 INCA1 NM_006612.6(KIF1C):c.1111G>A (p.Ala371Thr) SNV Uncertain significance 424675 rs142056835 17:4908241-4908241 17:5004946-5004946
42 BICD2 NM_001003800.2(BICD2):c.269A>G (p.Lys90Arg) SNV Uncertain significance 235235 rs61754130 9:95491490-95491490 9:92729208-92729208
43 SETX NM_015046.7(SETX):c.4711G>A (p.Val1571Met) SNV Uncertain significance 424661 rs745970760 9:135202274-135202274 9:132326887-132326887
44 KIF5A NM_004984.4(KIF5A):c.572G>A (p.Arg191His) SNV Uncertain significance 424697 rs1488871976 12:57960979-57960979 12:57567196-57567196
45 AMPD2 NM_001368809.2(AMPD2):c.1180G>A (p.Val394Met) SNV Uncertain significance 424691 rs374249741 1:110170804-110170804 1:109628182-109628182
46 ARSI NM_001012301.4(ARSI):c.1114G>A (p.Asp372Asn) SNV Uncertain significance 424672 rs150211860 5:149677373-149677373 5:150297810-150297810
47 AP5Z1 NM_014855.3(AP5Z1):c.2053C>T (p.Arg685Cys) SNV Uncertain significance 424688 rs367867460 7:4830418-4830418 7:4790787-4790787
48 CCT5 NM_012073.5(CCT5):c.487G>A (p.Glu163Lys) SNV Uncertain significance 424664 rs552008894 5:10256222-10256222 5:10256110-10256110
49 MAG NM_002361.4(MAG):c.1646C>T (p.Ser549Leu) SNV Uncertain significance 424680 rs767886169 19:35802850-35802850 19:35311947-35311947
50 USP8 NM_005154.5(USP8):c.1084A>G (p.Ile362Val) SNV Uncertain significance 458311 rs768800460 15:50769562-50769562 15:50477365-50477365

Copy number variations for Hereditary Spastic Paraplegia from CNVD:

7
# CNVD ID Chromosome 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:

36
# Name Kegg Source Accession
1 Endocytosis hsa04144
2 Lysosome hsa04142

GO Terms for Hereditary Spastic Paraplegia

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

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.24 SPG7 SPAST REEP1 PLEKHG5 NIPA1 KIF5A
2 endoplasmic reticulum membrane GO:0005789 9.87 SPAST REEP1 GBA2 FA2H ERLIN2 CYP7B1
3 axon GO:0030424 9.73 SPG11 SACS PLEKHG5 KIF1A EPHB1 ATL1
4 endoplasmic reticulum tubular network GO:0071782 9.33 SPAST REEP1 ATL1
5 endoplasmic reticulum GO:0005783 9.32 WASHC5 SPAST REEP1 GBA2 FA2H ERLIN2
6 axon cytoplasm GO:1904115 9.26 SPG7 SPAST KIF5A KIF1A

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

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.72 GBA2 FA2H ERLIN2 DDHD2 CYP7B1
2 steroid metabolic process GO:0008202 9.61 GBA2 ERLIN2 CYP7B1
3 cholesterol metabolic process GO:0008203 9.43 GBA2 ERLIN2 CYP7B1
4 cytoskeleton-dependent intracellular transport GO:0030705 9.4 KIF5A KIF1A
5 synaptic vesicle transport GO:0048489 9.37 SPG11 KIF5A
6 peripheral nervous system myelin maintenance GO:0032287 9.16 SH3TC2 FA2H
7 retrograde neuronal dense core vesicle transport GO:1990049 8.96 KIF5A KIF1A
8 anterograde axonal transport GO:0008089 8.8 SPG7 SPAST KIF1A

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

# Name GO ID Score Top Affiliating Genes
1 microtubule binding GO:0008017 9.26 SPAST REEP1 KIF5A KIF1A
2 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 9.16 KIF5A KIF1A
3 ATPase activity GO:0016887 8.92 SPG7 SPAST KIF5A KIF1A

Sources for Hereditary Spastic Paraplegia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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