SPG4
MCID: SPS147
MIFTS: 55

Spastic Paraplegia 4, Autosomal Dominant (SPG4)

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 Spastic Paraplegia 4, Autosomal Dominant

MalaCards integrated aliases for Spastic Paraplegia 4, Autosomal Dominant:

Name: Spastic Paraplegia 4, Autosomal Dominant 56 73 29 13 6 71
Spg4 56 12 58 73
Autosomal Dominant Spastic Paraplegia Type 4 12 58
Hereditary Spastic Paraplegia 4 12 15
Fsp2 56 73
Familial Spastic Paraplegia, Autosomal Dominant, 2; Fsp2 56
Familial Spastic Paraplegia, Autosomal Dominant, 2 56
Familial Spastic Paraplegia Autosomal Dominant 2 73
Paraplegia, Spastic, Autosomal Dominant, Type 4 39
Autosomal Dominant Spastic Paraplegia 4 12

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant spastic paraplegia type 4
Inheritance: Autosomal dominant; Age of onset: All ages;

OMIM:

56
Miscellaneous:
genetic anticipation
insidious onset
progressive disorder
highly variable severity
variable age of onset (infancy to 63 years)
most common form of autosomal dominant hereditary spastic paraplegia (accounts for 40% of spg cases)
genetic heterogeneity, see spg3a

Inheritance:
autosomal dominant


HPO:

31
spastic paraplegia 4, autosomal dominant:
Inheritance autosomal dominant inheritance genetic anticipation
Onset and clinical course variable expressivity progressive insidious onset


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spastic Paraplegia 4, Autosomal Dominant

OMIM : 56 The hereditary spastic paraplegias (SPG, HSP) are a group of clinically and genetically diverse inherited disorders characterized predominantly by progressive lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated') or with other neurologic abnormalities ('complicated'). Pure SPG4 is the most common form of autosomal dominant hereditary SPG, comprising up to 45% of cases (Svenson et al., 2001; Crippa et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600). (182601)

MalaCards based summary : Spastic Paraplegia 4, Autosomal Dominant, also known as spg4, is related to spasticity and spastic paraparesis, and has symptoms including agitation, low back pain and urgency of micturition. An important gene associated with Spastic Paraplegia 4, Autosomal Dominant is SPAST (Spastin), and among its related pathways/superpathways is Endocytosis. The drug Anesthetics has been mentioned in the context of this disorder. Affiliated tissues include brain and spinal cord, and related phenotypes are babinski sign and lower limb spasticity

Disease Ontology : 12 A hereditary spastic paraplegia that is characterized by slowly progressive muscle weakness and spasticity and has material basis in mutation in the SPAST gene on chromosome 2p22.

UniProtKB/Swiss-Prot : 73 Spastic paraplegia 4, autosomal dominant: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.

Related Diseases for Spastic Paraplegia 4, Autosomal Dominant

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
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 Spastic Paraplegia 4, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 111)
# Related Disease Score Top Affiliating Genes
1 spasticity 31.0 WASHC5 SPG7 SPAST REEP1 KIF1A
2 spastic paraparesis 30.9 SPG7 SPG11 SPAST KIF1A
3 pure hereditary spastic paraplegia 30.6 SPAST RTN2 NIPA1 KIF5A ATL1
4 spastic paraplegia 3, autosomal dominant 30.3 ZFYVE26 WASHC5 SPG11 SPAST RTN2 REEP1
5 spastic paraplegia 13, autosomal dominant 28.6 SPG7 SPG21 SPG11 SPAST SLC33A1 RTN2
6 spastic paraplegia 6, autosomal dominant 27.9 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
7 paraplegia 27.8 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
8 hereditary spastic paraplegia 27.2 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
9 spastic paraplegia 31, autosomal dominant 27.1 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
10 spastic paraplegia 10, autosomal dominant 27.1 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
11 spastic paraplegia 4 11.5
12 spastic paraplegia 3a 10.5
13 primary lateral sclerosis, adult, 1 10.4 SPG7 SPAST
14 neuropathy, hereditary sensory, type id 10.4 KIF5A ATL1
15 spastic paraplegia 64, autosomal recessive 10.3 SPG21 SPG11
16 ataxia and polyneuropathy, adult-onset 10.3
17 epilepsy 10.3
18 spastic paraplegia 6 10.3
19 charcot-marie-tooth disease, axonal, type 2r 10.3 ZFYVE26 SPG21
20 spastic paraplegia 73, autosomal dominant 10.3 SPG21 REEP1 ATL1
21 spastic paraplegia 49, autosomal recessive 10.3 ZFYVE26 SPG21 SPG11
22 spastic paraplegia 45, autosomal recessive 10.3 SPG21 SPG11
23 spastic ataxia 2 10.2 REEP1 KIF1A
24 spastic paraplegia 55, autosomal recessive 10.2 ZFYVE26 SPG21 SPG11
25 spastic paraplegia 41, autosomal dominant 10.2 SPG21 SPAST KATNA1
26 peripheral nervous system disease 10.2
27 neuropathy 10.2
28 axonal neuropathy 10.2 ZFYVE26 SPG11 KIF5A
29 spastic paraplegia 28, autosomal recessive 10.2 SPG11 REEP1 AP5Z1
30 spastic paraplegia 27, autosomal recessive 10.2 SPG21 SLC33A1 REEP1
31 amyotrophic lateral sclerosis type 5 10.2 ZFYVE26 SPG11 AP5Z1
32 optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 10.2 RTN2 AP5Z1
33 spastic paraplegia, optic atrophy, and neuropathy 10.2 WASHC5 AP5Z1
34 machado-joseph disease 10.2
35 dementia 10.2
36 polyneuropathy 10.2
37 autosomal dominant cerebellar ataxia 10.2
38 constipation 10.2
39 autosomal dominant distal hereditary motor neuronopathy 10.1 REEP1 BSCL2 ATL1
40 complex hereditary spastic paraplegia 10.1 SPG7 SPG11 NIPA1 CYP7B1
41 charcot-marie-tooth disease, axonal, type 2k 10.1 KIF5A KIF1A
42 spastic paraplegia 57, autosomal recessive 10.1 SPG11 REEP1 KIF5A KIF1A
43 spastic paraplegia 63, autosomal recessive 10.1 SPG7 SPG21 SPG11 CYP7B1
44 spastic paraplegia 29, autosomal dominant 10.1 ZFYVE26 WASHC5 SPG21 SLC33A1
45 spastic paraplegia 25, autosomal recessive 10.1 ZFYVE26 WASHC5 SPG21 SLC33A1
46 mast syndrome 10.1 ZFYVE27 SPG21 SPG11 SPART
47 spastic paraplegia 34, x-linked 10.1 ZFYVE26 WASHC5 SPG21 SLC33A1
48 charcot-marie-tooth disease, axonal, type 2t 10.1 ZFYVE26 SPG21
49 spastic paraplegia 43, autosomal recessive 10.1 WASHC5 SPG11 SPAST SLC33A1 ATL1
50 spinal muscular atrophy, distal, autosomal recessive, 2 10.0 REEP1 BSCL2

Graphical network of the top 20 diseases related to Spastic Paraplegia 4, Autosomal Dominant:



Diseases related to Spastic Paraplegia 4, Autosomal Dominant

Symptoms & Phenotypes for Spastic Paraplegia 4, Autosomal Dominant

Human phenotypes related to Spastic Paraplegia 4, Autosomal Dominant:

58 31 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
2 lower limb spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0002061
3 functional motor deficit 58 31 frequent (33%) Frequent (79-30%) HP:0004302
4 ankle clonus 58 31 frequent (33%) Frequent (79-30%) HP:0011448
5 brisk reflexes 58 31 frequent (33%) Frequent (79-30%) HP:0001348
6 urinary urgency 58 31 frequent (33%) Frequent (79-30%) HP:0000012
7 lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0007340
8 leg muscle stiffness 58 31 frequent (33%) Frequent (79-30%) HP:0008969
9 impaired vibration sensation at ankles 58 31 frequent (33%) Frequent (79-30%) HP:0006938
10 cognitive impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0100543
11 dysarthria 58 31 occasional (7.5%) Occasional (29-5%) HP:0001260
12 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
13 distal amyotrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003693
14 urinary bladder sphincter dysfunction 58 31 occasional (7.5%) Occasional (29-5%) HP:0002839
15 hyperreflexia in upper limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0007350
16 intellectual disability 58 31 very rare (1%) Very rare (<4-1%) HP:0001249
17 ataxia 58 31 very rare (1%) Very rare (<4-1%) HP:0001251
18 seizure 31 very rare (1%) HP:0001250
19 seizures 58 Very rare (<4-1%)
20 spasticity 58 Frequent (79-30%)
21 nystagmus 31 HP:0000639
22 hyperreflexia 31 HP:0001347
23 memory impairment 31 HP:0002354
24 depressivity 31 HP:0000716
25 spastic paraplegia 31 HP:0001258
26 aggressive behavior 31 HP:0000718
27 dementia 31 HP:0000726
28 disinhibition 31 HP:0000734
29 paraplegia 31 HP:0010550
30 apathy 31 HP:0000741
31 urinary incontinence 31 HP:0000020
32 spastic gait 31 HP:0002064
33 agitation 31 HP:0000713
34 impaired vibration sensation in the lower limbs 31 HP:0002166
35 degeneration of the lateral corticospinal tracts 31 HP:0002314
36 low back pain 31 HP:0003419

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
memory impairment
lower limb spasticity
spastic gait
degeneration of the lateral corticospinal tracts
more
Genitourinary Bladder:
urinary incontinence
urinary urgency
sphincter disturbances

Skeletal Spine:
lower back pain

Neurologic Behavioral Psychiatric Manifestations:
disinhibition
apathy
agitation
depression
aggression

Head And Neck Eyes:
nystagmus (rare)

Neurologic Peripheral Nervous System:
decreased vibratory sense in the lower limbs

Clinical features from OMIM:

182601

UMLS symptoms related to Spastic Paraplegia 4, Autosomal Dominant:


agitation, low back pain, urgency of micturition, abnormal pyramidal signs

MGI Mouse Phenotypes related to Spastic Paraplegia 4, Autosomal Dominant:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.73 ATL1 BSCL2 KATNA1 KIF1A KIF5A REEP1
2 nervous system MP:0003631 9.36 BSCL2 KATNA1 KIF1A KIF5A REEP1 SLC33A1

Drugs & Therapeutics for Spastic Paraplegia 4, Autosomal Dominant

Drugs for Spastic Paraplegia 4, Autosomal Dominant (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anesthetics

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Studying Cognition in SPG4 Compared to Healthy Controls Completed NCT03104088
2 Incidence of Unanticipated Difficult Airway Using an Objective Airway Score Versus a Standard Clinical Airway Assessment, The DIFFICAIR Trial - A Cluster-randomized Clinical Trial on 28 Anaesthesia Departments With 70,000 Patients Registered in the Danish Anaesthesia Database Completed NCT01718561
3 Studying Non-motor Symptoms in Patients With Hereditary Spastic Paraplegia (HSP) Compared to Healthy Controls Recruiting NCT03204773
4 Studying the Presymptomatic and Early Phase of SPG4 Recruiting NCT03206190
5 Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31 Recruiting NCT02859428

Search NIH Clinical Center for Spastic Paraplegia 4, Autosomal Dominant

Genetic Tests for Spastic Paraplegia 4, Autosomal Dominant

Genetic tests related to Spastic Paraplegia 4, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 4, Autosomal Dominant 29 SPAST

Anatomical Context for Spastic Paraplegia 4, Autosomal Dominant

MalaCards organs/tissues related to Spastic Paraplegia 4, Autosomal Dominant:

40
Brain, Spinal Cord

Publications for Spastic Paraplegia 4, Autosomal Dominant

Articles related to Spastic Paraplegia 4, Autosomal Dominant:

(show top 50) (show all 292)
# Title Authors PMID Year
1
A multi-exonic SPG4 duplication underlies sex-dependent penetrance of hereditary spastic paraplegia in a large Brazilian pedigree. 56 6 61
17895902 2007
2
Clinical features of hereditary spastic paraplegia due to spastin mutation. 56 6 61
16832076 2006
3
Hereditary spastic paraplegia: clinical genetic study of 15 families. 56 6 61
15210521 2004
4
Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree. 61 56 6
12471215 2002
5
Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia. 61 56 6
11309678 2001
6
Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. 6 61 56
10699187 2000
7
A fine integrated map of the SPG4 locus excludes an expanded CAG repeat in chromosome 2p-linked autosomal dominant spastic paraplegia. 56 6 61
10493830 1999
8
Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations. 56 6
15248095 2004
9
Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family. 61 56
20857310 2011
10
Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence. 56 61
19652142 2009
11
Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4. 61 56
18401025 2008
12
Linkage to a known gene but no mutation identified: comprehensive reanalysis of SPG4 HSP pedigrees reveals large deletions as the sole cause. 61 56
17345589 2007
13
Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia. 56 61
17098887 2007
14
Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia. 56 61
16682546 2006
15
Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases. 56 61
16055926 2006
16
Unexpected pathogenic mechanism of a novel mutation in the coding sequence of SPG4 (spastin). 61 6
16476945 2006
17
Large deletion involving the 5'-UTR in the spastin gene caused mild phenotype of autosomal dominant hereditary spastic paraplegia. 61 6
15637712 2005
18
A new SPG4 mutation in a variant form of spastic paraplegia with congenital arachnoid cysts. 56 61
15159500 2004
19
Further evidence of dementia in SPG4-linked autosomal dominant hereditary spastic paraplegia. 61 56
14872021 2004
20
Spastic Paraplegia 4 61 6
20301339 2003
21
Spectrum of SPG4 mutations in a large collection of North American families with hereditary spastic paraplegia. 56 61
11843700 2002
22
A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia. 6 61
12202986 2002
23
Phenotype of AD-HSP due to mutations in the SPAST gene: comparison with AD-HSP without mutations. 61 56
11134375 2000
24
Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis. 56 61
11015453 2000
25
Hereditary spastic paraplegia caused by mutations in the SPG4 gene. 6 61
11039577 2000
26
Intrafamilial variability in hereditary spastic paraplegia associated with an SPG4 gene mutation. 6 61
10980739 2000
27
Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation. 61 56
10891911 2000
28
Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. 61 6
10610178 1999
29
CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients. 61 56
9736780 1998
30
Phenotype of autosomal dominant spastic paraplegia linked to chromosome 2. 56 61
8931574 1996
31
Hereditary spastic paraplegia: gain-of-function mechanisms revealed by new transgenic mouse. 6
30520996 2019
32
Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses. 56
24451228 2014
33
Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia. 56
20154342 2010
34
Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia. 56
18701882 2009
35
A second leaky splice-site mutation in the spastin gene. 6
11704932 2001
36
Hereditary Spastic Paraplegia Overview 6
20301682 2000
37
Subclinical cognitive impairment in autosomal dominant "pure" hereditary spastic paraplegia. 56
10528866 1999
38
Linkage of AD HSP and cognitive impairment to chromosome 2p: haplotype and phenotype analysis indicates variable expression and low or delayed penetrance. 56
9781032 1998
39
Clinical heterogeneity of familial spastic paraplegia linked to chromosome 2p21. 56
9618065 1998
40
Autosomal dominant pure spastic paraplegia: a clinical, paraclinical, and genetic study. 56
9436729 1998
41
CAG repeat expansion in autosomal dominant pure spastic paraplegia linked to chromosome 2p21-p24. 56
9302257 1997
42
Locus heterogeneity, anticipation and reduction of the chromosome 2p minimal candidate region in autosomal dominant familial spastic paraplegia. 56
10732810 1997
43
Linkage of a locus for autosomal dominant familial spastic paraplegia to chromosome 2p markers. 56
7849714 1994
44
Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p. 56
7833913 1994
45
The dpy-30 gene encodes an essential component of the Caenorhabditis elegans dosage compensation machinery. 56
7982580 1994
46
Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. 56
8252041 1993
47
The autosomal dominant form of "pure" familial spastic paraplegia: clinical findings and linkage analysis of a large pedigree. 56
3587641 1987
48
Familial spastic paraplegia-clinical and pathologic studies in a large kindred. 56
703033 1978
49
Selective dorsal rhizotomy for spasticity of genetic etiology. 61
32300873 2020
50
Overlapping neuropathological findings in an asymptomatic SPAST gene mutation carrier. 61
32213280 2020

Variations for Spastic Paraplegia 4, Autosomal Dominant

ClinVar genetic disease variations for Spastic Paraplegia 4, Autosomal Dominant:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SPAST NC_000002.12:g.(?_32114638)_(32157637_?)deldeletion Pathogenic 417455 2:32339707-32382706 2:32114638-32157637
2 SPAST NC_000002.12:g.(?_32063611)_(32064246_?)deldeletion Pathogenic 417454 2:32288680-32289315 2:32063611-32064246
3 SPAST NM_014946.3(SPAST):c.410del (p.Glu137fs)deletion Pathogenic 409033 rs1060502229 2:32289310-32289310 2:32064241-32064241
4 SPAST NM_199436.1(SPAST):c.390_391delinsGGT (p.Leu131fs)indel Pathogenic 409034 rs1060502230 2:32289290-32289291 2:32064221-32064222
5 SPAST NM_014946.3(SPAST):c.1173+1G>ASNV Pathogenic 409030 rs1060502226 2:32352092-32352092 2:32127023-32127023
6 SPAST NM_014946.3(SPAST):c.1276C>G (p.Leu426Val)SNV Pathogenic 409031 rs1060502227 2:32361662-32361662 2:32136593-32136593
7 SPAST NM_014946.3(SPAST):c.127G>T (p.Glu43Ter)SNV Pathogenic 409028 rs573642949 2:32289027-32289027 2:32063958-32063958
8 SPAST NM_014946.3(SPAST):c.1729-1G>ASNV Pathogenic 419590 rs1064793976 2:32379442-32379442 2:32154373-32154373
9 SPAST NM_014946.3(SPAST):c.(?_1729)_(1851_?)deldeletion Pathogenic 437841 2:32379443-32379565 2:32154374-32154496
10 SPAST NM_014946.3(SPAST):c.734C>G (p.Ser245Ter)SNV Pathogenic 448453 rs1553314896 2:32339758-32339758 2:32114689-32114689
11 SPAST NM_014946.3(SPAST):c.838C>T (p.Gln280Ter)SNV Pathogenic 448456 rs1553314948 2:32339862-32339862 2:32114793-32114793
12 SPAST NM_014946.3(SPAST):c.1164G>T (p.Lys388Asn)SNV Pathogenic 450255 rs1553316838 2:32352082-32352082 2:32127013-32127013
13 SPAST NC_000002.12:g.(?_32126928)_(32128499_?)deldeletion Pathogenic 468558 2:32126928-32128499
14 SPAST NC_000002.12:g.(?_32063812)_(32154516_?)deldeletion Pathogenic 468557 2:32063812-32154516
15 SPAST NC_000002.12:g.(?_32136543)_(32137208_?)deldeletion Pathogenic 468559 2:32136543-32137208
16 SPAST NC_000002.12:g.(?_32063812)_(32116232_?)deldeletion Pathogenic 468556 2:32063812-32116232
17 SPAST NM_014946.3(SPAST):c.562del (p.Ala188fs)deletion Pathogenic 468573 rs1553400002 2:32314649-32314649 2:32089580-32089580
18 SPAST NM_014946.3(SPAST):c.1684C>T (p.Arg562Ter)SNV Pathogenic 448449 rs121908518 2:32370073-32370073 2:32145004-32145004
19 SPAST NM_014946.3(SPAST):c.1494-2A>CSNV Pathogenic 468568 rs1218081251 2:32366971-32366971 2:32141902-32141902
20 SPAST NM_014946.3(SPAST):c.421C>T (p.Gln141Ter)SNV Pathogenic 468571 rs1485703744 2:32312566-32312566 2:32087497-32087497
21 SPAST NM_014946.3(SPAST):c.883dup (p.Thr295fs)duplication Pathogenic 468576 rs1553315181 2:32340779-32340780 2:32115710-32115711
22 SPAST NM_014946.3(SPAST):c.1018_1022del (p.Val339_Lys340insTer)deletion Pathogenic 468560 rs1553315321 2:32341199-32341203 2:32116130-32116134
23 SPAST NM_014946.3(SPAST):c.422_425del (p.Gln141fs)deletion Pathogenic 468572 rs1553399472 2:32312567-32312570 2:32087498-32087501
24 SPAST NM_014946.3(SPAST):c.6_7del (p.Pro4fs)deletion Pathogenic 468574 rs1553394366 2:32288906-32288907 2:32063837-32063838
25 SPAST NM_014946.3(SPAST):c.870G>A (p.Lys290=)SNV Pathogenic 468575 rs1421791559 2:32339894-32339894 2:32114825-32114825
26 SPAST NM_014946.3(SPAST):c.1215_1219del (p.Asn405fs)deletion Pathogenic 468562 rs1553317032 2:32353515-32353519 2:32128446-32128450
27 SPAST NM_014946.3(SPAST):c.1412G>A (p.Gly471Asp)SNV Pathogenic 468565 rs1553318274 2:32362036-32362036 2:32136967-32136967
28 SPAST NM_014946.3(SPAST):c.1442_1443insA (p.Val482fs)insertion Pathogenic 468564 rs1553318313 2:32362206-32362207 2:32137137-32137138
29 SPAST NM_014946.3(SPAST):c.1169T>A (p.Met390Lys)SNV Pathogenic 488605 rs1131691977 2:32352087-32352087 2:32127018-32127018
30 SPAST NM_014946.3(SPAST):c.1484C>T (p.Ala495Val)SNV Pathogenic 488606 rs1553318347 2:32362248-32362248 2:32137179-32137179
31 SPAST NM_014946.3(SPAST):c.870+1G>ASNV Pathogenic 523508 rs1553314978 2:32339895-32339895 2:32114826-32114826
32 SPAST NC_000002.12:g.(?_32114618)_(32128499_?)deldeletion Pathogenic 536453 2:32339687-32353568 2:32114618-32128499
33 SPAST NM_014946.3(SPAST):c.156T>G (p.Tyr52Ter)SNV Pathogenic 536435 rs1553394497 2:32289056-32289056 2:32063987-32063987
34 SPAST NM_014946.3(SPAST):c.1252G>T (p.Glu418Ter)SNV Pathogenic 536439 rs1553318164 2:32361638-32361638 2:32136569-32136569
35 SPAST NM_014946.3(SPAST):c.1103T>C (p.Phe368Ser)SNV Pathogenic 536436 rs1553316799 2:32352021-32352021 2:32126952-32126952
36 SPAST NM_014946.3(SPAST):c.1577_1580del (p.Gly526fs)deletion Pathogenic 536440 rs1553319298 2:32368442-32368445 2:32143373-32143376
37 SPAST NM_014946.3(SPAST):c.444G>A (p.Trp148Ter)SNV Pathogenic 536448 rs1553399493 2:32312589-32312589 2:32087520-32087520
38 SPAST NM_014946.3(SPAST):c.166_175del (p.Tyr55_Pro56insTer)deletion Pathogenic 536450 rs1553394509 2:32289066-32289075 2:32063997-32064006
39 SPAST NM_014946.3(SPAST):c.328_340del (p.Gly110fs)deletion Pathogenic 536443 rs1410418105 2:32289224-32289236 2:32064155-32064167
40 SPAST NM_014946.3(SPAST):c.1494G>C (p.Arg498Ser)SNV Pathogenic 536434 rs1553319075 2:32366973-32366973 2:32141904-32141904
41 SPAST NM_014946.3(SPAST):c.1573C>T (p.Gln525Ter)SNV Pathogenic 536451 rs1553319296 2:32368441-32368441 2:32143372-32143372
42 SPAST NM_014946.3(SPAST):c.1375A>G (p.Arg459Gly)SNV Pathogenic 559624 rs1553318238 2:32361999-32361999 2:32136930-32136930
43 SPAST NC_000002.12:g.(?_32136543)_(32147278_?)deldeletion Pathogenic 584125 2:32361612-32372347 2:32136543-32147278
44 SPAST NC_000002.12:g.(?_32063812)_(32064266_?)deldeletion Pathogenic 583912 2:32288881-32289335 2:32063812-32064266
45 SPAST NC_000002.12:g.(?_32114618)_(32147278_?)deldeletion Pathogenic 584023 2:32339687-32372347 2:32114618-32147278
46 SPAST NM_014946.3(SPAST):c.1493+2_1493+5deldeletion Pathogenic 568108 rs1558337180 2:32362256-32362259 2:32137187-32137190
47 SPAST NM_014946.3(SPAST):c.1494-2A>GSNV Pathogenic 569227 rs1218081251 2:32366971-32366971 2:32141902-32141902
48 SPAST NM_014946.3(SPAST):c.1728+1G>ASNV Pathogenic 566838 rs587777754 2:32372328-32372328 2:32147259-32147259
49 SPAST NM_199436.1(SPAST):c.622_623AC[3] (p.His209_Thr210insTer)short repeat Pathogenic 577409 rs1558323426 2:32339742-32339743 2:32114673-32114674
50 SPAST NM_014946.3(SPAST):c.1617-1G>ASNV Pathogenic 574791 rs1553319526 2:32370005-32370005 2:32144936-32144936

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 4, Autosomal Dominant:

73 (show top 50) (show all 77)
# Symbol AA change Variation ID SNP ID
1 SPAST p.Ser362Cys VAR_010195 rs121908509
2 SPAST p.Arg424Gly VAR_010196
3 SPAST p.Cys448Tyr VAR_010197 rs121908510
4 SPAST p.Arg499Cys VAR_010198 rs121908511
5 SPAST p.Asp584His VAR_010199
6 SPAST p.Leu378Gln VAR_019439 rs155331681
7 SPAST p.Asn386Ser VAR_019440 rs121908514
8 SPAST p.Met390Val VAR_019441 rs797044850
9 SPAST p.Arg503Leu VAR_019442
10 SPAST p.Leu534Pro VAR_019444
11 SPAST p.Thr614Ile VAR_019445
12 SPAST p.Ile344Lys VAR_019448 rs121908513
13 SPAST p.Ser407Arg VAR_019450
14 SPAST p.Ala551Tyr VAR_019451
15 SPAST p.Thr615Ile VAR_019452
16 SPAST p.Leu195Val VAR_026758
17 SPAST p.Ile406Val VAR_026759 rs587777757
18 SPAST p.Asp493Gly VAR_026760
19 SPAST p.Arg499His VAR_026761 rs878854991
20 SPAST p.Arg503Trp VAR_026762 rs864622162
21 SPAST p.Trp607Cys VAR_026763
22 SPAST p.Gln347Lys VAR_027206
23 SPAST p.Pro361Leu VAR_027207
24 SPAST p.Gly370Arg VAR_027208
25 SPAST p.Phe381Cys VAR_027209
26 SPAST p.Asn386Lys VAR_027210
27 SPAST p.Lys388Arg VAR_027211
28 SPAST p.Ser399Leu VAR_027212 rs155331702
29 SPAST p.Leu426Val VAR_027213 rs106050222
30 SPAST p.Pro435Leu VAR_027214
31 SPAST p.Ser436Phe VAR_027215
32 SPAST p.Asp441Gly VAR_027216 rs121908512
33 SPAST p.Arg459Gly VAR_027217 rs155331823
34 SPAST p.Arg460Cys VAR_027218 rs878854990
35 SPAST p.Arg460Leu VAR_027219
36 SPAST p.Asp470Val VAR_027220 rs121908516
37 SPAST p.Ala485Val VAR_027221
38 SPAST p.Pro489Leu VAR_027222
39 SPAST p.Glu512Asp VAR_027223
40 SPAST p.Asp555Asn VAR_027224
41 SPAST p.Ala556Val VAR_027225
42 SPAST p.Gly559Asp VAR_027226 rs864622179
43 SPAST p.Arg562Gly VAR_027227 rs121908518
44 SPAST p.Arg562Gln VAR_027228 rs863224923
45 SPAST p.Ser413Leu VAR_067568
46 SPAST p.Glu454Lys VAR_067571
47 SPAST p.Arg460Ser VAR_067572
48 SPAST p.Pro293Leu VAR_067632 rs773193617
49 SPAST p.Arg364Thr VAR_067636
50 SPAST p.Leu378Arg VAR_067637

Expression for Spastic Paraplegia 4, Autosomal Dominant

Search GEO for disease gene expression data for Spastic Paraplegia 4, Autosomal Dominant.

Pathways for Spastic Paraplegia 4, Autosomal Dominant

Pathways related to Spastic Paraplegia 4, Autosomal Dominant according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.49 ZFYVE27 WASHC5 SPG21 SPART KIF5A CHMP1B

GO Terms for Spastic Paraplegia 4, Autosomal Dominant

Cellular components related to Spastic Paraplegia 4, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.28 ZFYVE27 ZFYVE26 WASHC5 SPG21 SPG11 SPAST
2 endoplasmic reticulum GO:0005783 9.97 ZFYVE27 WASHC5 SPAST SLC33A1 RTN2 REEP1
3 endoplasmic reticulum membrane GO:0005789 9.86 ZFYVE27 SPAST SLC33A1 RTN2 REEP1 CYP7B1
4 endosome GO:0005768 9.85 ZFYVE27 WASHC5 SPG21 SPAST NIPA1 CHMP1B
5 microtubule GO:0005874 9.78 SPAST KIF5A KIF1A KATNA1
6 integral component of endoplasmic reticulum membrane GO:0030176 9.63 ZFYVE27 RTN2 BSCL2
7 lipid droplet GO:0005811 9.58 SPAST SPART BSCL2
8 midbody GO:0030496 9.35 ZFYVE26 SPAST SPART KATNA1 CHMP1B
9 endoplasmic reticulum tubular network GO:0071782 9.33 ZFYVE27 REEP1 ATL1
10 axon cytoplasm GO:1904115 8.92 SPG7 SPAST KIF5A KIF1A

Biological processes related to Spastic Paraplegia 4, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell division GO:0051301 9.55 ZFYVE26 SPAST SPART KATNA1 CHMP1B
2 cytoskeleton-dependent intracellular transport GO:0030705 9.4 KIF5A KIF1A
3 lipid droplet organization GO:0034389 9.37 SPART BSCL2
4 synaptic vesicle transport GO:0048489 9.32 SPG11 KIF5A
5 microtubule severing GO:0051013 9.26 SPAST KATNA1
6 retrograde neuronal dense core vesicle transport GO:1990049 8.96 KIF5A KIF1A
7 anterograde axonal transport GO:0008089 8.8 SPG7 SPAST KIF1A

Molecular functions related to Spastic Paraplegia 4, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.25 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
2 ATPase activity GO:0016887 9.46 SPAST KIF5A KIF1A KATNA1
3 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 9.26 KIF5A KIF1A
4 microtubule binding GO:0008017 9.02 SPAST REEP1 KIF5A KIF1A KATNA1
5 microtubule-severing ATPase activity GO:0008568 8.96 SPAST KATNA1

Sources for Spastic Paraplegia 4, Autosomal Dominant

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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