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 drugs Anesthetics and Central Nervous System Depressants have been mentioned in the context of this disorder. Affiliated tissues include spinal cord, brain and eye, and related phenotypes are babinski sign and lower limb muscle weakness

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 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 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 30.4 SPAST RTN2 NIPA1 KIF5A ATL1
4 spastic paraplegia 3, autosomal dominant 29.9 ZFYVE26 WASHC5 SPG11 SPAST RTN2 REEP1
5 spastic paraplegia 13, autosomal dominant 28.8 SPG7 SPAST SLC33A1 RTN2 REEP1 NIPA1
6 paraplegia 27.2 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
7 spastic paraplegia 6, autosomal dominant 27.1 ZFYVE27 ZFYVE26 WASHC5 SPG21 SPG11 SPAST
8 spastic paraplegia 10, autosomal dominant 27.1 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
9 spastic paraplegia 31, autosomal dominant 26.8 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
10 hereditary spastic paraplegia 26.7 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 spinocerebellar ataxia, autosomal recessive 20 10.3 ZFYVE26 SPG11
16 ataxia and polyneuropathy, adult-onset 10.3
17 epilepsy 10.3
18 spastic paraplegia 6 10.3
19 spastic ataxia 2 10.3 REEP1 KIF1A
20 spastic paraplegia 64, autosomal recessive 10.3 SPG7 SPG21 SPG11
21 spastic paraplegia 63, autosomal recessive 10.3 SPG21 SPG11
22 charcot-marie-tooth disease, axonal, type 2r 10.3 ZFYVE26 SPG21
23 spastic paraplegia 27, autosomal recessive 10.3 SPG21 SLC33A1
24 spastic paraplegia 49, autosomal recessive 10.2 ZFYVE26 SPG21 SPG11
25 pseudobulbar palsy 10.2 SPART KIF5A
26 peripheral nervous system disease 10.2
27 neuropathy 10.2
28 spastic paraplegia 55, autosomal recessive 10.2 ZFYVE26 SPG21 SPG11
29 spastic paraplegia 41, autosomal dominant 10.2 SPG21 SPAST KATNA1
30 neuronopathy, distal hereditary motor, type va 10.2 REEP1 BSCL2
31 spastic paraplegia 77, autosomal recessive 10.2 ZFYVE26 SPG11 CYP7B1
32 machado-joseph disease 10.1
33 dementia 10.1
34 polyneuropathy 10.1
35 autosomal dominant cerebellar ataxia 10.1
36 constipation 10.1
37 spastic paraplegia 11, autosomal recessive 10.1 ZFYVE26 SPG7 SPG21 SPG11
38 charcot-marie-tooth disease, axonal, type 2k 10.1 KIF5A KIF1A
39 spastic paraplegia 24, autosomal recessive 10.1 SPG7 SPG21 CYP7B1
40 motor peripheral neuropathy 10.1 SPG11 REEP1 BSCL2
41 spastic paraplegia 57, autosomal recessive 10.1 SPG11 REEP1 KIF5A KIF1A
42 complex hereditary spastic paraplegia 10.1 SPG7 SPG11 NIPA1 CYP7B1
43 spastic paraplegia 28, autosomal recessive 10.1 SPG7 SPG11 REEP1 CYP7B1
44 charcot-marie-tooth disease, axonal, type 2t 10.1 ZFYVE26 SPG21
45 spastic paraplegia 34, x-linked 10.0 ZFYVE26 WASHC5 SPG21 SLC33A1
46 spastic paraplegia 29, autosomal dominant 10.0 ZFYVE26 WASHC5 SPG21 SLC33A1
47 spastic paraplegia 37, autosomal dominant 10.0 ZFYVE26 WASHC5 SPG21 SLC33A1
48 spastic paraplegia 25, autosomal recessive 10.0 ZFYVE26 WASHC5 SPG21 SLC33A1
49 spastic paraplegia 61, autosomal recessive 10.0 SPG21 SPAST RTN2 REEP1 ATL1
50 mast syndrome 10.0 ZFYVE27 SPG21 SPG11 SPART

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

Symptoms via clinical synopsis from OMIM:

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

Skeletal Spine:
lower back pain

Neurologic Behavioral Psychiatric Manifestations:
agitation
disinhibition
apathy
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 9.36 ATL1 BSCL2 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
2 Central Nervous System Depressants

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
Spinal Cord, Brain, Eye, Bone, Skin, Temporal Lobe

Publications for Spastic Paraplegia 4, Autosomal Dominant

Articles related to Spastic Paraplegia 4, Autosomal Dominant:

(show top 50) (show all 285)
# Title Authors PMID Year
1
A multi-exonic SPG4 duplication underlies sex-dependent penetrance of hereditary spastic paraplegia in a large Brazilian pedigree. 61 56 6
17895902 2007
2
Clinical features of hereditary spastic paraplegia due to spastin mutation. 61 56 6
16832076 2006
3
Hereditary spastic paraplegia: clinical genetic study of 15 families. 61 56 6
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. 61 56 6
10699187 2000
7
A fine integrated map of the SPG4 locus excludes an expanded CAG repeat in chromosome 2p-linked autosomal dominant spastic paraplegia. 61 56 6
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. 61 56
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. 61 56
17098887 2007
14
Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia. 61 56
16682546 2006
15
Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases. 61 56
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. 61 56
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. 61 56
11843700 2002
22
A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia. 61 6
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. 61 56
11015453 2000
25
Hereditary spastic paraplegia caused by mutations in the SPG4 gene. 61 6
11039577 2000
26
Intrafamilial variability in hereditary spastic paraplegia associated with an SPG4 gene mutation. 61 6
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. 61 56
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
Non-motor symptoms are relevant and possibly treatable in hereditary spastic paraplegia type 4 (SPG4). 61
31646384 2020
50
SPG8 mutations in Italian families: clinical data and literature review. 61
31814071 2019

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 deletion Pathogenic 219048 2:32373679-32384445 2:32148610-32159376
2 SPAST deletion Pathogenic 219049 2:32372792-32389594 2:32147726-32164528
3 SPAST deletion Pathogenic 219050 2:32378898-32384398 2:32153843-32159343
4 SPAST deletion Pathogenic 219051 2:32374427-32388831 2:32149358-32163762
5 SLC30A6 , SPAST deletion Pathogenic 219052 2:32378643-32403264 2:32153575-32178196
6 SPAST NM_014946.3(SPAST):c.1729-884_*1715deldeletion Pathogenic 219053 2:32378559-32381280 2:32153490-32156211
7 SLC30A6 , SPAST deletion Pathogenic 219062 2:32342697-32403350 2:32117629-32178282
8 SPAST deletion Pathogenic 219063 2:32282852-32295403 2:32057783-32070334
9 SLC30A6 , SPAST deletion Pathogenic 219054 2:32378673-32397052 2:32153604-32171983
10 SLC30A6 , SPAST deletion Pathogenic 219055 2:32372815-32398557 2:32147746-32173488
11 SPAST duplication Pathogenic 219056 2:32365580-32371821
12 BIRC6 , NLRC4 , SLC30A6 , SPAST , TTC27 , YIPF4 deletion Pathogenic 219057 2:32327163-32886455
13 DPY30 , SPAST deletion Pathogenic 219058 2:32260443-32347688 2:32035374-32122619
14 SPAST deletion Pathogenic 219059 2:32329723-32373142 2:32104654-32148073
15 BIRC6 , NLRC4 , SLC30A6 , SPAST , YIPF4 deletion Pathogenic 219060 2:32362824-32817794
16 SLC30A6 , SPAST deletion Pathogenic 219061 2:32313171-32408919 2:32088102-32183850
17 NLRC4 , SLC30A6 , SPAST deletion Pathogenic 219064 2:32302047-32472162 2:32076979-32247094
18 SPAST deletion Pathogenic 219065 2:32356943-32372914 2:32131874-32147845
19 SPAST deletion Pathogenic 219066 2:32302137-32351058 2:32077068-32125989
20 SPAST deletion Pathogenic 219067 2:32340402-32345422 2:32115334-32120354
21 SPAST NM_014946.3(SPAST):c.1688-378_1728+1541deldeletion Pathogenic 219068 2:32371908-32373867 2:32146839-32148798
22 SPAST duplication Pathogenic 219069 2:32353207-32359908
23 SPAST deletion Pathogenic 219070 2:32291779-32357195 2:32066710-32132126
24 SPAST deletion Pathogenic 219071 2:32282760-32303254 2:32057691-32078185
25 SPAST deletion Pathogenic 219072 2:32332674-32340934 2:32107605-32115865
26 SPAST deletion Pathogenic 219073 2:32376112-32381206 2:32151043-32156137
27 SPAST deletion Pathogenic 219074 2:32288217-32292251 2:32063148-32067182
28 SPAST deletion Pathogenic 219075 2:32308157-32341651 2:32083106-32116600
29 SPAST deletion Pathogenic 219076 2:32274911-32291246 2:32049842-32066177
30 SLC30A6 , SPAST deletion Pathogenic 219077 2:32347622-32392375 2:32122553-32167306
31 SLC30A6 , SPAST deletion Pathogenic 219078 2:32370423-32402099 2:32145356-32177032
32 SPAST deletion Pathogenic 219079 2:32291802-32364656 2:32066734-32139588
33 SPAST deletion Pathogenic 219086 2:32288708-32305196 2:32063639-32080127
34 BIRC6 , LTBP1 , NLRC4 , SLC30A6 , SPAST , TTC27 , YIPF4 deletion Pathogenic 219087 2:32348594-33632523
35 SPAST deletion Pathogenic 219088 2:32350954-32360289 2:32125886-32135221
36 SPAST NM_014946.3(SPAST):c.683-1277_870+399deldeletion Pathogenic 219080 2:32338430-32340293 2:32113361-32115224
37 SPAST deletion Pathogenic 219081 2:32352108-32379647 2:32127040-32154579
38 SPAST deletion Pathogenic 219082 2:32360319-32381228 2:32135250-32156159
39 SPAST deletion Pathogenic 219083 2:32372832-32390406 2:32147763-32165337
40 SPAST deletion Pathogenic 219084 2:32365295-32374446 2:32140226-32149377
41 SLC30A6 , SPAST deletion Pathogenic 219085 2:32372803-32396866 2:32147734-32171797
42 SPAST deletion Pathogenic 219089 2:32308541-32367923 2:32083472-32142854
43 SPAST deletion Pathogenic 219090 2:32338733-32350391 2:32113664-32125322
44 SPAST deletion Pathogenic 219091 2:32339714-32347794 2:32114645-32122725
45 SPAST deletion Pathogenic 219092 2:32351059-32359958 2:32125992-32134891
46 SLC30A6 , SPAST deletion Pathogenic 219093 2:32321557-32422090 2:32096488-32197021
47 SPAST duplication Pathogenic 219094 2:32358735-32362780
48 DPY30 , SPAST deletion Pathogenic 219095 2:32263919-32333722 2:32038850-32108653
49 SPAST NM_014946.3(SPAST):c.1245+1G>ASNV Pathogenic 226113 rs875989878 2:32353549-32353549 2:32128480-32128480
50 SPAST NM_014946.3(SPAST):c.1085C>G (p.Ser362Cys)SNV Pathogenic 5657 rs121908509 2:32341268-32341268 2:32116199-32116199

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 11.5 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 10.21 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 9.83 ZFYVE27 WASHC5 SPG21 SPAST CHMP1B
5 axon GO:0030424 9.78 ZFYVE27 SPG11 KIF1A ATL1
6 microtubule GO:0005874 9.76 SPAST KIF5A KIF1A KATNA1
7 integral component of endoplasmic reticulum membrane GO:0030176 9.58 ZFYVE27 RTN2 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 lipid droplet organization GO:0034389 9.37 SPART BSCL2
3 synaptic vesicle transport GO:0048489 9.32 SPG11 KIF5A
4 microtubule severing GO:0051013 9.26 SPAST KATNA1
5 retrograde neuronal dense core vesicle transport GO:1990049 8.96 KIF5A KIF1A
6 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 10.19 ZFYVE27 ZFYVE26 WASHC5 SPG7 SPG21 SPG11
2 ATPase activity GO:0016887 9.46 SPAST KIF5A KIF1A KATNA1
3 microtubule binding GO:0008017 9.02 SPAST REEP1 KIF5A KIF1A KATNA1
4 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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