SPG4
MCID: SPS147
MIFTS: 50

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 57 74 29 13 6 72
Spg4 57 12 59 74
Autosomal Dominant Spastic Paraplegia Type 4 12 59
Hereditary Spastic Paraplegia 4 12 15
Fsp2 57 74
Familial Spastic Paraplegia, Autosomal Dominant, 2; Fsp2 57
Familial Spastic Paraplegia, Autosomal Dominant, 2 57
Familial Spastic Paraplegia Autosomal Dominant 2 74
Paraplegia, Spastic, Autosomal Dominant, Type 4 40
Autosomal Dominant Spastic Paraplegia 4 12

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant spastic paraplegia type 4
Inheritance: Autosomal dominant; Age of onset: All ages;

OMIM:

57
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:

32
spastic paraplegia 4, autosomal dominant:
Inheritance autosomal dominant inheritance genetic anticipation
Onset and clinical course variable expressivity progressive insidious onset


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110792
MeSH 44 D015419
ICD10 33 G11.4
MESH via Orphanet 45 C536865
ICD10 via Orphanet 34 G11.4
UMLS via Orphanet 73 C1866855
Orphanet 59 ORPHA100985
MedGen 42 C1866855
UMLS 72 C1866855

Summaries for Spastic Paraplegia 4, Autosomal Dominant

OMIM : 57 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). The drugs Central Nervous System Depressants and Anesthetics have been mentioned in the context of this disorder. Affiliated tissues include brain and spinal cord, 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 : 74 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 1
Spastic Paraplegia 10 Spastic Paraplegia 12
Spastic Paraplegia 13 Spastic Paraplegia 14
Spastic Paraplegia 15 Spastic Paraplegia 16
Spastic Paraplegia 17 Spastic Paraplegia 18
Spastic Paraplegia 19 Spastic Paraplegia 24
Spastic Paraplegia 25 Spastic Paraplegia 26
Spastic Paraplegia 29 Spastic Paraplegia 3
Spastic Paraplegia 31 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 47
Spastic Paraplegia 51 Spastic Paraplegia 5a
Spastic Paraplegia 5b Spastic Paraplegia 6
Spastic Paraplegia 9 Spastic Paraplegia Type 49
Autosomal Recessive Spastic Paraplegia Type 60 Autosomal Recessive Spastic Paraplegia Type 59
Autosomal Recessive Spastic Paraplegia Type 69 Autosomal Recessive Spastic Paraplegia Type 70
Autosomal Recessive Spastic Paraplegia Type 71 Autosomal Recessive Spastic Paraplegia Type 66
Autosomal Recessive Spastic Paraplegia Type 67 Autosomal Dominant Spastic Paraplegia Type 9b

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

(show top 50) (show all 59)
# Related Disease Score Top Affiliating Genes
1 spasticity 31.2 SPG7 SPAST
2 spastic paraparesis 30.7 SPG7 SPG11 SPAST
3 spastic paraplegia 10 30.3 SPAST KIF5A
4 spastic paraplegia 13, autosomal dominant 29.5 SPAST ERLIN2 ATL1
5 amyotrophic lateral sclerosis 1 29.3 SPG11 SPAST SLC33A1
6 spastic paraplegia 3, autosomal dominant 29.1 SPG11 SPAST RTN2 REEP1 NIPA1 ATL1
7 spastic paraplegia 31, autosomal dominant 29.0 SPG11 SPAST RTN2 REEP1 ATL1
8 spastic paraplegia 10, autosomal dominant 28.5 SPG11 RTN2 REEP1 KIF5A ATL1
9 spastic paraplegia 6, autosomal dominant 27.3 SPAST SLC33A1 REEP1 NIPA1 KIF5A ERLIN2
10 paraplegia 26.4 SPG7 SPG11 SPAST SLC33A1 RTN2 REEP1
11 hereditary spastic paraplegia 26.4 SPG7 SPG11 SPAST SLC33A1 RTN2 REEP1
12 spastic paraplegia 4 11.5
13 spastic paraplegia 3a 10.5
14 primary lateral sclerosis, adult, 1 10.3 SPG7 SPAST
15 ataxia and polyneuropathy, adult-onset 10.3
16 epilepsy 10.3
17 spastic paraplegia 6 10.3
18 peripheral nervous system disease 10.2
19 neuropathy 10.2
20 pure hereditary spastic paraplegia 10.2
21 spastic paraplegia 15, autosomal recessive 10.2 SPG7 SPG11
22 spastic paraplegia 49, autosomal recessive 10.2 SPG7 SPG11
23 machado-joseph disease 10.1
24 dementia 10.1
25 polyneuropathy 10.1
26 autosomal dominant cerebellar ataxia 10.1
27 constipation 10.1
28 spastic paraplegia 11, autosomal recessive 10.1 SPG7 SPG11
29 spastic paraplegia 32, autosomal recessive 10.0 SPG7 SPG11 ATL1
30 candidiasis, familial, 1 10.0
31 migraine with or without aura 1 10.0
32 muscular dystrophy, scapulohumeral 10.0
33 aceruloplasminemia 10.0
34 spastic paraplegia 38, autosomal dominant 10.0
35 endogenous depression 10.0
36 spondylosis 10.0
37 lateral sclerosis 10.0
38 temporal lobe epilepsy 10.0
39 amyloidosis 10.0
40 diabetes mellitus 10.0
41 muscular dystrophy 10.0
42 arachnoid cysts 10.0
43 spastic paraplegia 13 10.0
44 spastic paraplegia 31 10.0
45 dementia - subcortical 10.0
46 spastic paraplegia 33, autosomal dominant 9.9 SPAST RTN2 REEP1
47 spastic paraplegia 2, x-linked 9.9 RTN2 REEP1 ATL1
48 spastic paraplegia 48, autosomal recessive 9.9 SPG11 ERLIN2
49 spastic paraplegia 47, autosomal recessive 9.8 REEP1 ERLIN2
50 spastic paraplegia 39, autosomal recessive 9.8 REEP1 ERLIN2

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:

59 32 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 59 32 frequent (33%) Frequent (79-30%) HP:0003487
2 lower limb muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0007340
3 brisk reflexes 59 32 frequent (33%) Frequent (79-30%) HP:0001348
4 lower limb spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0002061
5 ankle clonus 59 32 frequent (33%) Frequent (79-30%) HP:0011448
6 urinary urgency 59 32 frequent (33%) Frequent (79-30%) HP:0000012
7 functional motor deficit 59 32 frequent (33%) Frequent (79-30%) HP:0004302
8 leg muscle stiffness 59 32 frequent (33%) Frequent (79-30%) HP:0008969
9 impaired vibration sensation at ankles 59 32 frequent (33%) Frequent (79-30%) HP:0006938
10 dysarthria 59 32 occasional (7.5%) Occasional (29-5%) HP:0001260
11 cognitive impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0100543
12 pes cavus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001761
13 urinary bladder sphincter dysfunction 59 32 occasional (7.5%) Occasional (29-5%) HP:0002839
14 distal amyotrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0003693
15 hyperreflexia in upper limbs 59 32 occasional (7.5%) Occasional (29-5%) HP:0007350
16 intellectual disability 59 32 very rare (1%) Very rare (<4-1%) HP:0001249
17 seizures 59 32 very rare (1%) Very rare (<4-1%) HP:0001250
18 ataxia 59 32 very rare (1%) Very rare (<4-1%) HP:0001251
19 nystagmus 32 HP:0000639
20 depressivity 32 HP:0000716
21 spasticity 59 Frequent (79-30%)
22 hyperreflexia 32 HP:0001347
23 memory impairment 32 HP:0002354
24 aggressive behavior 32 HP:0000718
25 agitation 32 HP:0000713
26 dementia 32 HP:0000726
27 spastic paraplegia 32 HP:0001258
28 impaired vibration sensation in the lower limbs 32 HP:0002166
29 degeneration of the lateral corticospinal tracts 32 HP:0002314
30 spastic gait 32 HP:0002064
31 urinary incontinence 32 HP:0000020
32 disinhibition 32 HP:0000734
33 apathy 32 HP:0000741
34 paraplegia 32 HP:0010550
35 low back pain 32 HP:0003419

Symptoms via clinical synopsis from OMIM:

57
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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.17 ATL1 KIF5A REEP1 SLC33A1 SPAST SPG11

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 Central Nervous System Depressants
2 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:

41
Brain, Spinal Cord

Publications for Spastic Paraplegia 4, Autosomal Dominant

Articles related to Spastic Paraplegia 4, Autosomal Dominant:

(show top 50) (show all 274)
# Title Authors PMID Year
1
A multi-exonic SPG4 duplication underlies sex-dependent penetrance of hereditary spastic paraplegia in a large Brazilian pedigree. 38 8 71
17895902 2007
2
Clinical features of hereditary spastic paraplegia due to spastin mutation. 38 8 71
16832076 2006
3
Hereditary spastic paraplegia: clinical genetic study of 15 families. 38 8 71
15210521 2004
4
Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree. 38 8 71
12471215 2002
5
Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia. 38 8 71
11309678 2001
6
Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. 38 8 71
10699187 2000
7
Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations. 8 71
15248095 2004
8
Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family. 38 8
20857310 2011
9
Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence. 38 8
19652142 2009
10
Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4. 38 8
18401025 2008
11
Linkage to a known gene but no mutation identified: comprehensive reanalysis of SPG4 HSP pedigrees reveals large deletions as the sole cause. 38 8
17345589 2007
12
Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia. 38 8
17098887 2007
13
Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia. 38 8
16682546 2006
14
Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases. 38 8
16055926 2006
15
Unexpected pathogenic mechanism of a novel mutation in the coding sequence of SPG4 (spastin). 38 71
16476945 2006
16
Large deletion involving the 5'-UTR in the spastin gene caused mild phenotype of autosomal dominant hereditary spastic paraplegia. 38 71
15637712 2005
17
A new SPG4 mutation in a variant form of spastic paraplegia with congenital arachnoid cysts. 38 8
15159500 2004
18
Further evidence of dementia in SPG4-linked autosomal dominant hereditary spastic paraplegia. 38 8
14872021 2004
19
Spastic Paraplegia 4 38 71
20301339 2003
20
Spectrum of SPG4 mutations in a large collection of North American families with hereditary spastic paraplegia. 38 8
11843700 2002
21
A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia. 38 71
12202986 2002
22
Phenotype of AD-HSP due to mutations in the SPAST gene: comparison with AD-HSP without mutations. 38 8
11134375 2000
23
Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis. 38 8
11015453 2000
24
Hereditary spastic paraplegia caused by mutations in the SPG4 gene. 38 71
11039577 2000
25
Intrafamilial variability in hereditary spastic paraplegia associated with an SPG4 gene mutation. 38 71
10980739 2000
26
Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation. 38 8
10891911 2000
27
Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. 38 71
10610178 1999
28
A fine integrated map of the SPG4 locus excludes an expanded CAG repeat in chromosome 2p-linked autosomal dominant spastic paraplegia. 38 71
10493830 1999
29
CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients. 38 8
9736780 1998
30
Phenotype of autosomal dominant spastic paraplegia linked to chromosome 2. 38 8
8931574 1996
31
Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses. 8
24451228 2014
32
Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia. 8
20154342 2010
33
Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia. 8
18701882 2009
34
A second leaky splice-site mutation in the spastin gene. 71
11704932 2001
35
Hereditary Spastic Paraplegia Overview 71
20301682 2000
36
Subclinical cognitive impairment in autosomal dominant "pure" hereditary spastic paraplegia. 8
10528866 1999
37
Clinical heterogeneity of familial spastic paraplegia linked to chromosome 2p21. 8
9618065 1998
38
Linkage of AD HSP and cognitive impairment to chromosome 2p: haplotype and phenotype analysis indicates variable expression and low or delayed penetrance. 8
9781032 1998
39
Autosomal dominant pure spastic paraplegia: a clinical, paraclinical, and genetic study. 8
9436729 1998
40
CAG repeat expansion in autosomal dominant pure spastic paraplegia linked to chromosome 2p21-p24. 8
9302257 1997
41
Locus heterogeneity, anticipation and reduction of the chromosome 2p minimal candidate region in autosomal dominant familial spastic paraplegia. 8
10732810 1997
42
Linkage of a locus for autosomal dominant familial spastic paraplegia to chromosome 2p markers. 8
7849714 1994
43
Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p. 8
7833913 1994
44
The dpy-30 gene encodes an essential component of the Caenorhabditis elegans dosage compensation machinery. 8
7982580 1994
45
Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. 8
8252041 1993
46
The autosomal dominant form of "pure" familial spastic paraplegia: clinical findings and linkage analysis of a large pedigree. 8
3587641 1987
47
Familial spastic paraplegia-clinical and pathologic studies in a large kindred. 8
703033 1978
48
Multiparametric rapid screening of neuronal process pathology for drug target identification in HSP patient-specific neurons. 38
31270336 2019
49
De novo SPAST mutations may cause a complex SPG4 phenotype. 38
31157359 2019
50
Novel ATL1 mutation in a Chinese family with hereditary spastic paraplegia: A case report and review of literature. 38
31236401 2019

Variations for Spastic Paraplegia 4, Autosomal Dominant

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

6 (show top 50) (show all 237)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SPAST NC_000002.11: g.(?_32339707)_(32382706_?)del deletion Pathogenic 2:32339707-32382706 2:32114638-32157637
2 SPAST NC_000002.11: g.(?_32288680)_(32289315_?)del deletion Pathogenic 2:32288680-32289315 2:32063611-32064246
3 SPAST NM_014946.3(SPAST): c.410del (p.Glu137fs) deletion Pathogenic rs1060502229 2:32289310-32289310 2:32064241-32064241
4 SPAST NM_014946.3(SPAST): c.390_391delinsGGT (p.Leu131fs) indel Pathogenic rs1060502230 2:32289290-32289291 2:32064221-32064222
5 SPAST NM_014946.3(SPAST): c.1173+1G> A single nucleotide variant Pathogenic rs1060502226 2:32352092-32352092 2:32127023-32127023
6 SPAST NM_014946.3(SPAST): c.1276C> G (p.Leu426Val) single nucleotide variant Pathogenic rs1060502227 2:32361662-32361662 2:32136593-32136593
7 SPAST NM_014946.3(SPAST): c.127G> T (p.Glu43Ter) single nucleotide variant Pathogenic rs573642949 2:32289027-32289027 2:32063958-32063958
8 SPAST NM_014946.3(SPAST): c.1729-1G> A single nucleotide variant Pathogenic rs1064793976 2:32379442-32379442 2:32154373-32154373
9 SPAST NM_014946.3(SPAST): c.(?_1729)_(1851_?)del (p.(?)) deletion Pathogenic 2:32379443-32379565 2:32154374-32154496
10 SPAST NM_014946.3(SPAST): c.734C> G (p.Ser245Ter) single nucleotide variant Pathogenic rs1553314896 2:32339758-32339758 2:32114689-32114689
11 SPAST NM_014946.3(SPAST): c.838C> T (p.Gln280Ter) single nucleotide variant Pathogenic rs1553314948 2:32339862-32339862 2:32114793-32114793
12 SPAST NM_014946.3(SPAST): c.1684C> T (p.Arg562Ter) single nucleotide variant Pathogenic rs121908518 2:32370073-32370073 2:32145004-32145004
13 SPAST NM_014946.3(SPAST): c.1164G> T (p.Lys388Asn) single nucleotide variant Pathogenic rs1553316838 2:32352082-32352082 2:32127013-32127013
14 SPAST deletion Pathogenic
15 SPAST deletion Pathogenic
16 SPAST deletion Pathogenic
17 SPAST deletion Pathogenic
18 SPAST NM_014946.3(SPAST): c.562del (p.Ala188fs) deletion Pathogenic rs1553400002 2:32314650-32314650 2:32089581-32089581
19 SPAST NM_014946.3(SPAST): c.421C> T (p.Gln141Ter) single nucleotide variant Pathogenic rs1485703744 2:32312566-32312566 2:32087497-32087497
20 SPAST NM_014946.3(SPAST): c.883dup (p.Thr295fs) duplication Pathogenic rs1553315181 2:32340783-32340783 2:32115714-32115714
21 SPAST NM_014946.3(SPAST): c.1018_1022del (p.Val339_Lys340insTer) deletion Pathogenic rs1553315321 2:32341201-32341205 2:32116132-32116136
22 SPAST NM_014946.3(SPAST): c.422_425del (p.Gln141fs) deletion Pathogenic rs1553399472 2:32312567-32312570 2:32087498-32087501
23 SPAST NM_014946.3(SPAST): c.6_7del (p.Pro4fs) deletion Pathogenic rs1553394366 2:32288906-32288907 2:32063837-32063838
24 SPAST NM_014946.3(SPAST): c.1494-2A> C single nucleotide variant Pathogenic rs1218081251 2:32366971-32366971 2:32141902-32141902
25 SPAST NM_014946.3(SPAST): c.1215_1219del (p.Asn405fs) deletion Pathogenic rs1553317032 2:32353518-32353522 2:32128449-32128453
26 SPAST NM_014946.3(SPAST): c.1412G> A (p.Gly471Asp) single nucleotide variant Pathogenic rs1553318274 2:32362036-32362036 2:32136967-32136967
27 SPAST NM_014946.3(SPAST): c.1442_1443insA (p.Val482fs) insertion Pathogenic rs1553318313 2:32362206-32362207 2:32137137-32137138
28 SPAST NM_014946.3(SPAST): c.1169T> A (p.Met390Lys) single nucleotide variant Pathogenic rs1131691977 2:32352087-32352087 2:32127018-32127018
29 SPAST NM_014946.3(SPAST): c.1484C> T (p.Ala495Val) single nucleotide variant Pathogenic rs1553318347 2:32362248-32362248 2:32137179-32137179
30 SPAST NM_014946.3(SPAST): c.870+1G> A single nucleotide variant Pathogenic rs1553314978 2:32339895-32339895 2:32114826-32114826
31 SPAST NC_000002.11: g.(?_32339687)_(32353568_?)del deletion Pathogenic 2:32339687-32353568 2:32114618-32128499
32 SPAST NM_014946.3(SPAST): c.156T> G (p.Tyr52Ter) single nucleotide variant Pathogenic rs1553394497 2:32289056-32289056 2:32063987-32063987
33 SPAST NM_014946.3(SPAST): c.1252G> T (p.Glu418Ter) single nucleotide variant Pathogenic rs1553318164 2:32361638-32361638 2:32136569-32136569
34 SPAST NM_014946.3(SPAST): c.1103T> C (p.Phe368Ser) single nucleotide variant Pathogenic rs1553316799 2:32352021-32352021 2:32126952-32126952
35 SPAST NM_014946.3(SPAST): c.1577_1580del (p.Gly526fs) deletion Pathogenic rs1553319298 2:32368445-32368448 2:32143376-32143379
36 SPAST NM_014946.3(SPAST): c.444G> A (p.Trp148Ter) single nucleotide variant Pathogenic rs1553399493 2:32312589-32312589 2:32087520-32087520
37 SPAST NM_014946.3(SPAST): c.166_175del (p.Tyr55_Pro56insTer) deletion Pathogenic rs1553394509 2:32289066-32289075 2:32063997-32064006
38 SPAST NM_014946.3(SPAST): c.328_340del (p.Gly110fs) deletion Pathogenic rs1410418105 2:32289228-32289240 2:32064159-32064171
39 SPAST NM_014946.3(SPAST): c.1085C> G (p.Ser362Cys) single nucleotide variant Pathogenic rs121908509 2:32341268-32341268 2:32116199-32116199
40 SPAST NM_014946.3(SPAST): c.1343G> A (p.Cys448Tyr) single nucleotide variant Pathogenic rs121908510 2:32361967-32361967 2:32136898-32136898
41 SPAST NM_014946.3(SPAST): c.1395del (p.Phe465_Leu466insTer) deletion Pathogenic rs587777751 2:32362019-32362019 2:32136950-32136950
42 SPAST NM_014946.3(SPAST): c.1495C> T (p.Arg499Cys) single nucleotide variant Pathogenic rs121908511 2:32366974-32366974 2:32141905-32141905
43 SPAST NM_014946.3(SPAST): c.1688-2A> G single nucleotide variant Pathogenic rs587777752 2:32372285-32372285 2:32147216-32147216
44 SPAST SPAST, LYS229TER single nucleotide variant Pathogenic
45 SPAST NM_014946.3(SPAST): c.453dup (p.Gly152fs) duplication Pathogenic rs587777753 2:32312598-32312598 2:32087529-32087529
46 SPAST NM_014946.3(SPAST): c.1322A> G (p.Asp441Gly) single nucleotide variant Pathogenic rs121908512 2:32361946-32361946 2:32136877-32136877
47 SPAST NM_014946.3(SPAST): c.1728+1G> C single nucleotide variant Pathogenic rs587777754 2:32372328-32372328 2:32147259-32147259
48 SPAST NM_014946.3(SPAST): c.1245+4A> G single nucleotide variant Pathogenic rs587777755 2:32353552-32353552 2:32128483-32128483
49 SPAST NM_014946.3(SPAST): c.1413+2dup duplication Pathogenic rs587777756 2:32362039-32362039 2:32136970-32136970
50 SPAST NM_014946.3(SPAST): c.1031T> A (p.Ile344Lys) single nucleotide variant Pathogenic rs121908513 2:32341214-32341214 2:32116145-32116145

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

74 (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

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 integral component of membrane GO:0016021 9.92 SPG7 SPAST SLC33A1 RTN2 REEP1 NIPA1
2 endoplasmic reticulum GO:0005783 9.63 SPAST SLC33A1 RTN2 REEP1 ERLIN2 ATL1
3 endoplasmic reticulum tubular network GO:0071782 9.26 REEP1 ATL1
4 axon cytoplasm GO:1904115 9.13 SPG7 SPAST KIF5A
5 endoplasmic reticulum membrane GO:0005789 9.1 SPAST SLC33A1 RTN2 REEP1 ERLIN2 ATL1
6 membrane GO:0016020 10.02 SPG7 SPAST SLC33A1 RTN2 REEP1 NIPA1

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

# Name GO ID Score Top Affiliating Genes
1 axonogenesis GO:0007409 9.16 SPAST ATL1
2 anterograde axonal transport GO:0008089 8.96 SPG7 SPAST
3 synaptic vesicle transport GO:0048489 8.62 SPG11 KIF5A

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

# Name GO ID Score Top Affiliating Genes
1 microtubule binding GO:0008017 8.8 SPAST REEP1 KIF5A

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 HGMD
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69 SNOMED-CT via HPO
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73 UMLS via Orphanet
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