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, 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 58 76 30 13 6 74
Spg4 58 12 60 76
Autosomal Dominant Spastic Paraplegia Type 4 12 60
Hereditary Spastic Paraplegia 4 12 15
Fsp2 58 76
Familial Spastic Paraplegia, Autosomal Dominant, 2; Fsp2 58
Familial Spastic Paraplegia, Autosomal Dominant, 2 58
Familial Spastic Paraplegia Autosomal Dominant 2 76
Paraplegia, Spastic, Autosomal Dominant, Type 4 41
Autosomal Dominant Spastic Paraplegia 4 12

Characteristics:

Orphanet epidemiological data:

60
autosomal dominant spastic paraplegia type 4
Inheritance: Autosomal dominant; Age of onset: All ages;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
genetic anticipation
insidious onset
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


HPO:

33
spastic paraplegia 4, autosomal dominant:
Onset and clinical course variable expressivity insidious onset progressive
Inheritance genetic anticipation autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Spastic Paraplegia 4, Autosomal Dominant

OMIM : 58 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 spastic paraparesis and spastic paraplegia 10, 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 drug Metronidazole has been mentioned in the context of this disorder. Affiliated tissues include skin, bone 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 : 76 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 Hereditary Spastic Paraplegia 23
Hereditary Spastic Paraplegia 51 Hereditary Spastic Paraplegia 72
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 all 42)
# Related Disease Score Top Affiliating Genes
1 spastic paraparesis 30.5 SPAST SPG11 SPG7
2 spastic paraplegia 10 30.4 KIF5A SPAST
3 spastic paraplegia 3, autosomal dominant 29.6 ATL1 NIPA1 REEP1 RTN2 SPAST SPG11
4 paraplegia 28.2 ATL1 ERLIN2 KIF5A NIPA1 REEP1 RTN2
5 hereditary spastic paraplegia 28.1 ATL1 ERLIN2 KIF5A NIPA1 REEP1 RTN2
6 spastic paraplegia 4 11.4
7 spastic paraplegia 3a 10.4
8 primary lateral sclerosis, adult, 1 10.2 SPAST SPG7
9 spastic paraplegia 15, autosomal recessive 10.1 SPG11 SPG7
10 spastic paraplegia 17, autosomal dominant 10.1
11 spastic paraplegia 49, autosomal recessive 10.1 SPG11 SPG7
12 spastic paraplegia 11, autosomal recessive 10.1 SPG11 SPG7
13 spasticity 10.0 SPAST SPG7
14 spastic paraplegia 32, autosomal recessive 10.0 ATL1 SPG11 SPG7
15 machado-joseph disease 10.0
16 multiple sclerosis 10.0
17 cognitive function 1, social 10.0
18 aceruloplasminemia 10.0
19 dementia 10.0
20 epilepsy 10.0
21 peripheral nervous system disease 10.0
22 neuropathy 10.0
23 arachnoid cysts 10.0
24 spastic paraplegia 33, autosomal dominant 9.9 REEP1 RTN2 SPAST
25 spastic paraplegia 2, x-linked 9.9 ATL1 REEP1 RTN2
26 spastic paraplegia 47, autosomal recessive 9.9 ERLIN2 REEP1
27 spastic paraplegia 48, autosomal recessive 9.9 ERLIN2 SPG11
28 spastic paraplegia 39, autosomal recessive 9.9 ERLIN2 REEP1
29 spastic paraplegia 30, autosomal recessive 9.9 ERLIN2 REEP1
30 spastic paraplegia 35, autosomal recessive 9.9 ERLIN2 SPG11
31 spastic paraplegia 13, autosomal dominant 9.8 ATL1 ERLIN2 SPAST
32 spastic paraplegia 61, autosomal recessive 9.8 ATL1 REEP1 RTN2 SPAST
33 amyotrophic lateral sclerosis 1 9.7 SLC33A1 SPAST SPG11
34 axonal neuropathy 9.7 KIF5A SPG11
35 spastic paraplegia 18, autosomal recessive 9.7 ERLIN2 NIPA1 REEP1
36 masa syndrome 9.6 ATL1 NIPA1 REEP1 SPAST SPG11
37 spastic paraplegia 31, autosomal dominant 9.6 ATL1 REEP1 RTN2 SPAST SPG11
38 spastic paraplegia 10, autosomal dominant 9.4 ATL1 KIF5A REEP1 RTN2 SPG11
39 spastic paraplegia 42, autosomal dominant 9.4 ERLIN2 NIPA1 REEP1 SLC33A1
40 spastic paraplegia 8, autosomal dominant 9.3 ATL1 ERLIN2 NIPA1 REEP1 SPG11
41 spastic paraplegia 12, autosomal dominant 9.0 ATL1 ERLIN2 KIF5A REEP1 RTN2 SPAST
42 spastic paraplegia 6, autosomal dominant 8.7 ATL1 ERLIN2 KIF5A NIPA1 REEP1 SLC33A1

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:

60 33 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 60 33 frequent (33%) Frequent (79-30%) HP:0003487
2 lower limb muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0007340
3 brisk reflexes 60 33 frequent (33%) Frequent (79-30%) HP:0001348
4 lower limb spasticity 60 33 frequent (33%) Frequent (79-30%) HP:0002061
5 ankle clonus 60 33 frequent (33%) Frequent (79-30%) HP:0011448
6 urinary urgency 60 33 frequent (33%) Frequent (79-30%) HP:0000012
7 functional motor deficit 60 33 frequent (33%) Frequent (79-30%) HP:0004302
8 leg muscle stiffness 60 33 frequent (33%) Frequent (79-30%) HP:0008969
9 impaired vibration sensation at ankles 60 33 frequent (33%) Frequent (79-30%) HP:0006938
10 dysarthria 60 33 occasional (7.5%) Occasional (29-5%) HP:0001260
11 cognitive impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0100543
12 pes cavus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001761
13 urinary bladder sphincter dysfunction 60 33 occasional (7.5%) Occasional (29-5%) HP:0002839
14 hyperreflexia in upper limbs 60 33 occasional (7.5%) Occasional (29-5%) HP:0007350
15 distal amyotrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0003693
16 intellectual disability 60 33 very rare (1%) Very rare (<4-1%) HP:0001249
17 seizures 60 33 very rare (1%) Very rare (<4-1%) HP:0001250
18 ataxia 60 33 very rare (1%) Very rare (<4-1%) HP:0001251
19 nystagmus 33 HP:0000639
20 depressivity 33 HP:0000716
21 spasticity 60 Frequent (79-30%)
22 hyperreflexia 33 HP:0001347
23 memory impairment 33 HP:0002354
24 aggressive behavior 33 HP:0000718
25 agitation 33 HP:0000713
26 dementia 33 HP:0000726
27 spastic paraplegia 33 HP:0001258
28 impaired vibration sensation in the lower limbs 33 HP:0002166
29 degeneration of the lateral corticospinal tracts 33 HP:0002314
30 spastic gait 33 HP:0002064
31 urinary incontinence 33 HP:0000020
32 disinhibition 33 HP:0000734
33 apathy 33 HP:0000741
34 paraplegia 33 HP:0010550
35 low back pain 33 HP:0003419

Symptoms via clinical synopsis from OMIM:

58
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:

47
# 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
Metronidazole Approved Not Applicable 443-48-1 4173

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Studying Cognition in SPG4 Completed NCT03104088
2 The Effect of Virtual Simulation Training in Mastoidectomy Completed NCT02030873 Not Applicable
3 Preoperative Pain, Function, and Activity for Total Hip and Knee Arthroplasty Patients Completed NCT01248039
4 The Pre-SPG4 Study Recruiting NCT03206190 Not Applicable
5 Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31 Recruiting NCT02859428
6 Studying Non-motor Symptoms in HSP Recruiting NCT03204773

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 30 SPAST

Anatomical Context for Spastic Paraplegia 4, Autosomal Dominant

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

42
Skin, Bone, Eye

Publications for Spastic Paraplegia 4, Autosomal Dominant

Articles related to Spastic Paraplegia 4, Autosomal Dominant:

(show top 50) (show all 95)
# Title Authors Year
1
MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons. ( 30777884 )
2019
2
Resting state fMRI studies in SPG4-linked hereditary spastic paraplegia. ( 29249364 )
2018
3
Identification of a novel SPG4 tandem base substitution in a Chinese hereditary spastic paraplegia family. ( 27942873 )
2017
4
Cognitive Impairment Involving Social Cognition in SPG4 Hereditary Spastic Paraplegia. ( 27688599 )
2016
5
Erratum to: The neurological and ophthalmological manifestations of SPG4-related hereditary spastic paraplegia. ( 26837615 )
2016
6
Non-motor symptoms in patients with hereditary spastic paraplegia caused by SPG4 mutations. ( 26806216 )
2016
7
Gray and white matter alterations in hereditary spastic paraplegia type SPG4 and clinical correlations. ( 26050637 )
2015
8
Hereditary spastic paraplegia SPG4: what is known and not known about the disease. ( 26094131 )
2015
9
Multimodal MRI-based study in patients with SPG4 mutations. ( 25658484 )
2015
10
Novel splice site mutation of SPG4 in a Chinese family with hereditary spastic paraplegia. ( 24659419 )
2014
11
High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia. ( 25421405 )
2014
12
Genetic analysis of SPG4 and SPG3A genes in a cohort of Chinese patients with hereditary spastic paraplegia. ( 25454648 )
2014
13
Spin labeling artery method perfusion MRI study of SPG4 and SCA3/MJD. ( 25172988 )
2014
14
Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons. ( 24381312 )
2014
15
SPG4-related hereditary spastic paraplegia: frequency and mutation spectrum in Brazil. ( 24033003 )
2014
16
Diffusion tensor imaging in SPG11- and SPG4-linked hereditary spastic paraplegia. ( 23968121 )
2014
17
The neurological and ophthalmological manifestations of SPG4-related hereditary spastic paraplegia. ( 23238845 )
2013
18
Screening for the hereditary spastic paraplaegias SPG4 and SPG3A with the multiplex ligation-dependent probe amplification technique in a large population of affected individuals. ( 22203332 )
2013
19
Peripheral neuropathy in hereditary spastic paraplegia due to spastin (SPG4) mutation--a neurophysiological study using excitability techniques. ( 22192498 )
2012
20
Novel and recurrent spastin mutations in a large series of SPG4 Italian families. ( 22960362 )
2012
21
SPG4 gene promoter regulation via Elk1 transcription factor. ( 21395583 )
2011
22
A novel splicing mutation (c.870+3A>G) in SPG4 in a Korean family with hereditary spastic paraplegia. ( 19939411 )
2010
23
Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia. ( 20932283 )
2010
24
Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia. ( 19875132 )
2010
25
Evaluation of loss of function as an explanation for SPG4-based hereditary spastic paraplegia. ( 20430936 )
2010
26
Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence. ( 19652142 )
2009
27
The prevalence of hereditary spastic paraplegia and the occurrence of SPG4 mutations in Estonia. ( 19039240 )
2009
28
Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families. ( 18664244 )
2009
29
There might be more to SPG4! ( 19289473 )
2009
30
Novel SPG3A and SPG4 mutations in two patients with Silver syndrome. ( 19730024 )
2009
31
Novel human pathological mutations. Gene symbol: SPG4. Disease: spastic paraplegia, autosomal dominant. ( 19694023 )
2009
32
Novel human pathological mutations. Gene symbol: SPG4. Disease: spastic paraplegia, autosomal dominant. ( 19694022 )
2009
33
Compound heterozygosity in the SPG4 gene causes hereditary spastic paraplegia. ( 18190593 )
2008
34
Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4. ( 18401025 )
2008
35
A cryptic promoter in the first exon of the SPG4 gene directs the synthesis of the 60-kDa spastin isoform. ( 18613979 )
2008
36
Spastic paraplegia in Romania: high prevalence of SPG4 mutations. ( 17971434 )
2008
37
Mental deficiency in three families with SPG4 spastic paraplegia. ( 17957230 )
2008
38
Double-blind crossover trial of gabapentin in SPG4-linked hereditary spastic paraplegia. ( 17539946 )
2007
39
Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia. ( 17594340 )
2007
40
Possible anticipation in hereditary spastic paraplegia type 4 (SPG4). ( 17598599 )
2007
41
SPG4 founder effect in French Canadians with hereditary spastic paraplegia. ( 17598600 )
2007
42
An SPG3A whole gene deletion neither co-segregates with disease nor modifies phenotype in a hereditary spastic paraplegia family with a pathogenic SPG4 deletion. ( 17657515 )
2007
43
A multi-exonic SPG4 duplication underlies sex-dependent penetrance of hereditary spastic paraplegia in a large Brazilian pedigree. ( 17895902 )
2007
44
Isoform-specific increase of spastin stability by N-terminal missense variants including intragenic modifiers of SPG4 hereditary spastic paraplegia. ( 17916079 )
2007
45
Motor and somatosensory evoked potentials in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) linked to chromosome 2p, SPG4. ( 17720546 )
2007
46
Linkage to a known gene but no mutation identified: comprehensive reanalysis of SPG4 HSP pedigrees reveals large deletions as the sole cause. ( 17345589 )
2007
47
Analysis and mapping of CACNB4, CHRNA1, KCNJ3, SCN2A and SPG4, physiological candidate genes for porcine congenital progressive ataxia and spastic paresis. ( 17868079 )
2007
48
Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia. ( 17098887 )
2007
49
No correlation between amount of aberrant transcript and severity of phenotype in hereditary spastic paraplegia patients with a c.1242A > G splice mutation in the SPG4 gene. ( 16362530 )
2006
50
Gene symbol: SPAST (SPG4). Disease: Spastic paraparesis. Accession #Hm0552. ( 17297708 )
2006

Variations for Spastic Paraplegia 4, Autosomal Dominant

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

76 (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
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
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
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

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

6 (show top 50) (show all 404)
# Gene Variation Type Significance SNP ID Assembly Location
1 SPAST NM_014946.3(SPAST): c.1085C> G (p.Ser362Cys) single nucleotide variant Pathogenic rs121908509 GRCh37 Chromosome 2, 32341268: 32341268
2 SPAST NM_014946.3(SPAST): c.1085C> G (p.Ser362Cys) single nucleotide variant Pathogenic rs121908509 GRCh38 Chromosome 2, 32116199: 32116199
3 SPAST NM_014946.3(SPAST): c.1343G> A (p.Cys448Tyr) single nucleotide variant Pathogenic rs121908510 GRCh37 Chromosome 2, 32361967: 32361967
4 SPAST NM_014946.3(SPAST): c.1343G> A (p.Cys448Tyr) single nucleotide variant Pathogenic rs121908510 GRCh38 Chromosome 2, 32136898: 32136898
5 SPAST NM_014946.3(SPAST): c.1395delT (p.Leu466Terfs) deletion Pathogenic rs587777751 GRCh38 Chromosome 2, 32136950: 32136950
6 SPAST NM_014946.3(SPAST): c.1395delT (p.Leu466Terfs) deletion Pathogenic rs587777751 GRCh37 Chromosome 2, 32362019: 32362019
7 SPAST NM_014946.3(SPAST): c.1495C> T (p.Arg499Cys) single nucleotide variant Pathogenic rs121908511 GRCh37 Chromosome 2, 32366974: 32366974
8 SPAST NM_014946.3(SPAST): c.1495C> T (p.Arg499Cys) single nucleotide variant Pathogenic rs121908511 GRCh38 Chromosome 2, 32141905: 32141905
9 SPAST NM_014946.3(SPAST): c.1688-2A> G single nucleotide variant Pathogenic rs587777752 GRCh38 Chromosome 2, 32147216: 32147216
10 SPAST NM_014946.3(SPAST): c.1688-2A> G single nucleotide variant Pathogenic rs587777752 GRCh37 Chromosome 2, 32372285: 32372285
11 SPAST SPAST, LYS229TER single nucleotide variant Pathogenic
12 SPAST NM_014946.3(SPAST): c.453dupA (p.Gly152Argfs) duplication Pathogenic rs587777753 GRCh38 Chromosome 2, 32087529: 32087529
13 SPAST NM_014946.3(SPAST): c.453dupA (p.Gly152Argfs) duplication Pathogenic rs587777753 GRCh37 Chromosome 2, 32312598: 32312598
14 SPAST NM_014946.3(SPAST): c.1322A> G (p.Asp441Gly) single nucleotide variant Pathogenic rs121908512 GRCh37 Chromosome 2, 32361946: 32361946
15 SPAST NM_014946.3(SPAST): c.1322A> G (p.Asp441Gly) single nucleotide variant Pathogenic rs121908512 GRCh38 Chromosome 2, 32136877: 32136877
16 SPAST NM_014946.3(SPAST): c.1728+1G> C single nucleotide variant Pathogenic rs587777754 GRCh38 Chromosome 2, 32147259: 32147259
17 SPAST NM_014946.3(SPAST): c.1728+1G> C single nucleotide variant Pathogenic rs587777754 GRCh37 Chromosome 2, 32372328: 32372328
18 SPAST NM_014946.3(SPAST): c.1245+4A> G single nucleotide variant Pathogenic rs587777755 GRCh38 Chromosome 2, 32128483: 32128483
19 SPAST NM_014946.3(SPAST): c.1245+4A> G single nucleotide variant Pathogenic rs587777755 GRCh37 Chromosome 2, 32353552: 32353552
20 SPAST NM_014946.3(SPAST): c.1413+2dupT duplication Pathogenic rs587777756 GRCh38 Chromosome 2, 32136970: 32136970
21 SPAST NM_014946.3(SPAST): c.1413+2dupT duplication Pathogenic rs587777756 GRCh37 Chromosome 2, 32362039: 32362039
22 SPAST NM_014946.3(SPAST): c.1031T> A (p.Ile344Lys) single nucleotide variant Pathogenic rs121908513 GRCh37 Chromosome 2, 32341214: 32341214
23 SPAST NM_014946.3(SPAST): c.1031T> A (p.Ile344Lys) single nucleotide variant Pathogenic rs121908513 GRCh38 Chromosome 2, 32116145: 32116145
24 SPAST NM_014946.3(SPAST): c.1157A> G (p.Asn386Ser) single nucleotide variant Pathogenic rs121908514 GRCh37 Chromosome 2, 32352075: 32352075
25 SPAST NM_014946.3(SPAST): c.1157A> G (p.Asn386Ser) single nucleotide variant Pathogenic rs121908514 GRCh38 Chromosome 2, 32127006: 32127006
26 SPAST NM_014946.3(SPAST): c.1409A> T (p.Asp470Val) single nucleotide variant Pathogenic rs121908516 GRCh37 Chromosome 2, 32362033: 32362033
27 SPAST NM_014946.3(SPAST): c.1409A> T (p.Asp470Val) single nucleotide variant Pathogenic rs121908516 GRCh38 Chromosome 2, 32136964: 32136964
28 SPAST NM_014946.3(SPAST): c.131C> T (p.Ser44Leu) single nucleotide variant risk factor rs121908515 GRCh37 Chromosome 2, 32289031: 32289031
29 SPAST NM_014946.3(SPAST): c.131C> T (p.Ser44Leu) single nucleotide variant risk factor rs121908515 GRCh38 Chromosome 2, 32063962: 32063962
30 SPAST NM_014946.3(SPAST): c.1684C> G (p.Arg562Gly) single nucleotide variant Pathogenic rs121908518 GRCh37 Chromosome 2, 32370073: 32370073
31 SPAST NM_014946.3(SPAST): c.1684C> G (p.Arg562Gly) single nucleotide variant Pathogenic rs121908518 GRCh38 Chromosome 2, 32145004: 32145004
32 SPAST NM_014946.3(SPAST): c.-112_415+1779del deletion Pathogenic GRCh38 Chromosome 2, 32063720: 32066025
33 SPAST NM_014946.3(SPAST): c.-112_415+1779del deletion Pathogenic GRCh37 Chromosome 2, 32288789: 32291094
34 SPAST NM_014946.3(SPAST): c.1216A> G (p.Ile406Val) single nucleotide variant Likely pathogenic rs587777757 GRCh38 Chromosome 2, 32128450: 32128450
35 SPAST NM_014946.3(SPAST): c.1216A> G (p.Ile406Val) single nucleotide variant Likely pathogenic rs587777757 GRCh37 Chromosome 2, 32353519: 32353519
36 SPAST NM_014946.3(SPAST): c.1335C> A (p.Ser445Arg) single nucleotide variant Pathogenic rs121908519 GRCh37 Chromosome 2, 32361959: 32361959
37 SPAST NM_014946.3(SPAST): c.1335C> A (p.Ser445Arg) single nucleotide variant Pathogenic rs121908519 GRCh38 Chromosome 2, 32136890: 32136890
38 SPAST NG_008730.1: g.75057_79101dup duplication Pathogenic GRCh38 Chromosome 2, 32133667: 32137711
39 SPAST NG_008730.1: g.75057_79101dup duplication Pathogenic GRCh37 Chromosome 2, 32358736: 32362780
40 SPAST NM_014946.3(SPAST): c.1165A> G (p.Thr389Ala) single nucleotide variant Pathogenic rs786204132 GRCh37 Chromosome 2, 32352083: 32352083
41 SPAST NM_014946.3(SPAST): c.1165A> G (p.Thr389Ala) single nucleotide variant Pathogenic rs786204132 GRCh38 Chromosome 2, 32127014: 32127014
42 SPAST NM_014946.3(SPAST): c.1291C> T (p.Arg431Ter) single nucleotide variant Pathogenic rs786204126 GRCh37 Chromosome 2, 32361677: 32361677
43 SPAST NM_014946.3(SPAST): c.1291C> T (p.Arg431Ter) single nucleotide variant Pathogenic rs786204126 GRCh38 Chromosome 2, 32136608: 32136608
44 SPAST NM_014946.3(SPAST): c.1414-1G> C single nucleotide variant Pathogenic rs786204163 GRCh37 Chromosome 2, 32362177: 32362177
45 SPAST NM_014946.3(SPAST): c.1414-1G> C single nucleotide variant Pathogenic rs786204163 GRCh38 Chromosome 2, 32137108: 32137108
46 SPAST NM_014946.3(SPAST): c.1637G> A (p.Gly546Glu) single nucleotide variant Uncertain significance rs786204057 GRCh38 Chromosome 2, 32144957: 32144957
47 SPAST NM_014946.3(SPAST): c.1637G> A (p.Gly546Glu) single nucleotide variant Uncertain significance rs786204057 GRCh37 Chromosome 2, 32370026: 32370026
48 SPAST NM_014946.3(SPAST): c.683-9C> T single nucleotide variant Benign/Likely benign rs202209866 GRCh37 Chromosome 2, 32339698: 32339698
49 SPAST NM_014946.3(SPAST): c.683-9C> T single nucleotide variant Benign/Likely benign rs202209866 GRCh38 Chromosome 2, 32114629: 32114629
50 SPAST NM_014946.3(SPAST): c.1168A> G (p.Met390Val) single nucleotide variant Pathogenic rs797044850 GRCh37 Chromosome 2, 32352086: 32352086

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

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 ATL1 SPAST
2 anterograde axonal transport GO:0008089 8.96 SPAST SPG7
3 synaptic vesicle transport GO:0048489 8.62 KIF5A SPG11

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 KIF5A REEP1 SPAST

Sources for Spastic Paraplegia 4, Autosomal Dominant

3 CDC
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