SPG3
MCID: SPS215
MIFTS: 56

Spastic Paraplegia 3, Autosomal Dominant (SPG3)

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 3, Autosomal Dominant

MalaCards integrated aliases for Spastic Paraplegia 3, Autosomal Dominant:

Name: Spastic Paraplegia 3, Autosomal Dominant 58 76 74
Spg3a 58 12 76 56
Strumpell Disease 58 12 76
Fsp1 58 12 76
Autosomal Dominant Spastic Paraplegia Type 3 12 60
Spastic Paraplegia 3a, Autosomal Dominant 58 13
Hereditary Spastic Paraplegia 3a 12 15
Spg3 58 76
Familial Spastic Paraplegia, Autosomal Dominant, 1; Fsp1 58
Familial Spastic Paraplegia, Autosomal Dominant, 1 58
Autosomal Dominant Familial Spastic Paraplegia 1 12
Familial Spastic Paraplegia Autosomal Dominant 1 76
Paraplegia, Spastic, Autosomal Dominant, Type 3a 41
Autosomal Dominant Spastic Paraplegia 3 12
Spastic Paraplegia, Hereditary 74
Strumpell-Lorrain Syndrome 76
Strümpell Disease 60

Characteristics:

Orphanet epidemiological data:

60
autosomal dominant spastic paraplegia type 3
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Portugal),1-9/1000000 (Europe); Age of onset: Adult,Childhood;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
insidious onset
reduced penetrance
highly variable severity
usually shows early age at onset (range 1 to 7 years, mean 4.6 years)
later onset has been rarely reported (up to age 68 years)
most patients need assistance walking or are wheelchair-bound
variable progression


HPO:

33
spastic paraplegia 3, autosomal dominant:
Onset and clinical course variable expressivity incomplete penetrance insidious onset
Inheritance heterogeneous autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Spastic Paraplegia 3, Autosomal Dominant

OMIM : 58 The hereditary spastic paraplegias are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997). SPG is classified according to both the mode of inheritance (autosomal dominant, autosomal recessive (see 270800), and X-linked (see 303350)) and whether progressive spasticity occurs in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, and deafness. The major neuropathologic feature of autosomal dominant, uncomplicated SPG is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts (crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis, respectively). Spinocerebellar fibers are involved to a lesser extent. Since the description of 'pure' hereditary spastic paraparesis of late onset by Strumpell (1904), many 'complicated' forms of the disorder have been reported and the question as to whether a 'pure' form exists has been raised off and on. Probably in large part because of their exceptional length, the pyramidal tracts are unusually vulnerable to both acquired and genetic derangement. Although a majority of reported families have displayed recessive inheritance, 10 to 30% of families have a dominant pattern and in fact recessive inheritance of a 'pure' spastic paraplegia may be rare. (182600)

MalaCards based summary : Spastic Paraplegia 3, Autosomal Dominant, also known as spg3a, is related to spastic paraplegia 12, autosomal dominant and spastic paraplegia 4, autosomal dominant, and has symptoms including urgency of micturition, pain in lower limb and leg cramps. An important gene associated with Spastic Paraplegia 3, Autosomal Dominant is ATL1 (Atlastin GTPase 1), and among its related pathways/superpathways are ECM-receptor interaction and Presenilin-Mediated Signaling. The drugs Acetylcholine and Botulinum Toxins have been mentioned in the context of this disorder. Affiliated tissues include skin, bone and eye, and related phenotypes are babinski sign and lower limb spasticity

Disease Ontology : 12 A hereditary spastic paraplegia that is characterized by lower limb weakness and spasticity that is generally non-progressive or extremely slow and has material basis in mutation in the ATL1 gene on chromosome 14q22.

UniProtKB/Swiss-Prot : 76 Spastic paraplegia 3, 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 3, 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 3, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 35)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 12, autosomal dominant 31.6 ATL1 REEP1 RTN2 SPAST
2 spastic paraplegia 4, autosomal dominant 31.5 ATL1 NIPA1 REEP1 RTN2 SPAST SPG11
3 spastic paraplegia 8, autosomal dominant 31.4 ATL1 NIPA1 REEP1 SPG11
4 hereditary spastic paraplegia 31.3 ATL1 NIPA1 REEP1 RTN2 SPAST SPG11
5 paraplegia 30.4 ATL1 NIPA1 REEP1 RTN2 SPAST SPG11
6 spastic paraplegia 3a 11.4
7 spastic paraplegia 3 11.4
8 spondyloarthropathy 1 11.2
9 spastic paraplegia 9a, autosomal dominant 11.1
10 neuropathy, hereditary sensory, type id 11.1
11 spastic paraplegia 72, autosomal recessive 11.1
12 spastic paraplegia 80, autosomal dominant 11.1
13 spastic paraplegia 4 10.5
14 neuropathy 10.3
15 spastic paraplegia 32, autosomal recessive 10.3 ATL1 SPG11
16 spastic paraplegia 13, autosomal dominant 10.3 ATL1 SPAST
17 axonal neuropathy 10.2
18 hypotrichosis, congenital, with juvenile macular dystrophy 10.2 CDH1 CDH3
19 gastric signet ring cell adenocarcinoma 10.1 CDH1 SNAI1
20 spastic paraplegia 33, autosomal dominant 10.1 REEP1 RTN2 SPAST
21 spastic paraplegia 2, x-linked 10.1 ATL1 REEP1 RTN2
22 iga glomerulonephritis 10.1
23 spastic paraplegia 18, autosomal recessive 10.1 NIPA1 REEP1
24 ankylosis 10.1
25 spastic paraplegia 42, autosomal dominant 10.1 NIPA1 REEP1
26 crohn's colitis 10.1 CDH1 CDH3
27 spastic paraplegia 61, autosomal recessive 10.0 ATL1 REEP1 RTN2 SPAST
28 spastic paraplegia 17, autosomal dominant 10.0
29 ureteral disease 10.0 CDH1 SMAD2
30 spastic paraplegia 10, autosomal dominant 10.0 ATL1 REEP1 RTN2 SPG11
31 diffuse gastric cancer 10.0 CDH1 CDH3
32 spastic paraparesis 9.9 SPAST SPG11
33 spastic paraplegia 6, autosomal dominant 9.9 ATL1 NIPA1 REEP1 SPAST
34 spastic paraplegia 31, autosomal dominant 9.9 ATL1 REEP1 RTN2 SPAST SPG11
35 masa syndrome 9.7 ATL1 NIPA1 REEP1 SPAST SPG11

Graphical network of the top 20 diseases related to Spastic Paraplegia 3, Autosomal Dominant:



Diseases related to Spastic Paraplegia 3, Autosomal Dominant

Symptoms & Phenotypes for Spastic Paraplegia 3, Autosomal Dominant

Human phenotypes related to Spastic Paraplegia 3, Autosomal Dominant:

60 33 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 60 33 hallmark (90%) Very frequent (99-80%) HP:0003487
2 lower limb spasticity 60 33 hallmark (90%) Very frequent (99-80%) HP:0002061
3 distal lower limb muscle weakness 60 33 hallmark (90%) Very frequent (99-80%) HP:0009053
4 lower limb hyperreflexia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002395
5 ankle clonus 60 33 frequent (33%) Frequent (79-30%) HP:0011448
6 spastic gait 60 33 frequent (33%) Frequent (79-30%) HP:0002064
7 distal lower limb amyotrophy 60 33 frequent (33%) Frequent (79-30%) HP:0008944
8 toe walking 60 33 occasional (7.5%) Occasional (29-5%) HP:0040083
9 motor delay 60 33 occasional (7.5%) Occasional (29-5%) HP:0001270
10 urinary urgency 60 33 occasional (7.5%) Occasional (29-5%) HP:0000012
11 impaired vibratory sensation 60 33 occasional (7.5%) Occasional (29-5%) HP:0002495
12 intellectual disability, mild 33 occasional (7.5%) HP:0001256
13 hypoplasia of the corpus callosum 33 occasional (7.5%) HP:0002079
14 dysarthria 60 33 very rare (1%) Very rare (<4-1%) HP:0001260
15 growth delay 60 33 very rare (1%) Very rare (<4-1%) HP:0001510
16 rigidity 60 33 very rare (1%) Very rare (<4-1%) HP:0002063
17 bradykinesia 60 33 very rare (1%) Very rare (<4-1%) HP:0002067
18 frequent falls 60 33 very rare (1%) Very rare (<4-1%) HP:0002359
19 lower limb hypertonia 60 33 very rare (1%) Very rare (<4-1%) HP:0006895
20 hyperesthesia 60 33 very rare (1%) Very rare (<4-1%) HP:0100963
21 gait disturbance 60 Frequent (79-30%)
22 hyperreflexia 33 HP:0001347
23 scoliosis 33 HP:0002650
24 peripheral neuropathy 60 Occasional (29-5%)
25 pes cavus 33 HP:0001761
26 urinary bladder sphincter dysfunction 33 HP:0002839
27 spastic paraplegia 33 HP:0001258
28 lower limb muscle weakness 33 HP:0007340
29 impaired vibration sensation in the lower limbs 33 HP:0002166
30 degeneration of the lateral corticospinal tracts 33 HP:0002314
31 urinary incontinence 33 HP:0000020
32 paraplegia 33 HP:0010550

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
hyperreflexia
lower limb spasticity
spastic gait
delayed motor development
extensor plantar responses
more
Neurologic Peripheral Nervous System:
degeneration of the lateral corticospinal tracts
decreased vibratory sense in lower limbs after long disease duration

Skeletal Feet:
pes cavus in patients with early onset

Skeletal Spine:
scoliosis

Genitourinary Bladder:
urinary urgency
urinary incontinence
sphincter disturbances

Clinical features from OMIM:

182600

UMLS symptoms related to Spastic Paraplegia 3, Autosomal Dominant:


urgency of micturition, pain in lower limb, leg cramps

MGI Mouse Phenotypes related to Spastic Paraplegia 3, Autosomal Dominant:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.85 CDH1 CDH5 FN1 PECAM1 REEP1 RTN2
2 cardiovascular system MP:0005385 9.8 CDH1 CDH5 FN1 PECAM1 SMAD2 SNAI1
3 homeostasis/metabolism MP:0005376 9.61 CDH1 CDH5 FN1 NIPA1 PECAM1 REEP1
4 normal MP:0002873 9.17 CDH1 CDH5 FN1 SMAD2 SNAI1 SPAST

Drugs & Therapeutics for Spastic Paraplegia 3, Autosomal Dominant

Drugs for Spastic Paraplegia 3, Autosomal Dominant (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved, Investigational Phase 2, Phase 3 51-84-3 187
2 Botulinum Toxins Phase 2, Phase 3
3 Acetylcholine Release Inhibitors Phase 2, Phase 3
4 Neurotransmitter Agents Phase 2, Phase 3,Phase 1
5 Cholinergic Agents Phase 2, Phase 3
6
Sarpogrelate Investigational Phase 1 125926-17-2 5160
7 Fibrinolytic Agents Phase 1
8 Platelet Aggregation Inhibitors Phase 1
9 Serotonin Antagonists Phase 1
10 Serotonin Agents Phase 1
11
Serotonin Investigational, Nutraceutical Phase 1 50-67-9 5202
12
Choline Approved, Nutraceutical 62-49-7 305
13
Creatine Approved, Investigational, Nutraceutical 57-00-1 586
14 Aspartic Acid
15 N-Methylaspartate

Interventional clinical trials:

(show all 13)
# Name Status NCT ID Phase Drugs
1 Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia Completed NCT02604186 Phase 2, Phase 3
2 Physiotherapy in Hereditary Spastic Paraplegia Completed NCT03961906 Phase 2
3 Pharmacokinetics and Food Effect of Sarpogrelate HCl CR Formulation in Comparison to Immediate-release Formulation Completed NCT01841086 Phase 1 Anplag;UI03SPG300CT
4 Respiration Gated Laser Guided CT Lung Nodule Biopsy Unknown status NCT01236937 Not Applicable
5 Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy Completed NCT03627416 Not Applicable
6 Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis Completed NCT00023075
7 Studying Cognition in SPG4 Completed NCT03104088
8 Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31 Recruiting NCT02859428
9 Studying Non-motor Symptoms in HSP Recruiting NCT03204773
10 The Pre-SPG4 Study Recruiting NCT03206190 Not Applicable
11 Phenotype, Genotype & Biomarkers in ALS and Related Disorders Recruiting NCT02327845
12 Genetic and Physical Study of Childhood Nerve and Muscle Disorders Recruiting NCT01568658
13 A Patient Centric Motor Neuron Disease Activities of Daily Living Scale Enrolling by invitation NCT02852278

Search NIH Clinical Center for Spastic Paraplegia 3, Autosomal Dominant

Genetic Tests for Spastic Paraplegia 3, Autosomal Dominant

Anatomical Context for Spastic Paraplegia 3, Autosomal Dominant

MalaCards organs/tissues related to Spastic Paraplegia 3, Autosomal Dominant:

42
Skin, Bone, Eye

Publications for Spastic Paraplegia 3, Autosomal Dominant

Articles related to Spastic Paraplegia 3, Autosomal Dominant:

(show all 43)
# Title Authors Year
1
De novo mutations in SPG3A: a challenge in differential diagnosis and genetic counselling. ( 25637064 )
2015
2
ER network formation and membrane fusion by atlastin1/SPG3A disease variants. ( 25761634 )
2015
3
Pharmacologic rescue of axon growth defects in a human iPSC model of hereditary spastic paraplegia SPG3A. ( 24908668 )
2014
4
Genetic analysis of SPG4 and SPG3A genes in a cohort of Chinese patients with hereditary spastic paraplegia. ( 25454648 )
2014
5
Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation. ( 24473461 )
2014
6
SPG3A-linked hereditary spastic paraplegia associated with cerebral glucose hypometabolism. ( 23233086 )
2013
7
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
8
The p.Arg416Cys mutation in SPG3a gene associated with a pure form of spastic paraplegia. ( 22581552 )
2012
9
Hereditary spastic paraplegia associated with axonal neuropathy: a novel mutation of SPG3A in a large family. ( 21321493 )
2011
10
Late-onset hereditary spastic paraplegia with thin corpus callosum caused by a new SPG3A mutation. ( 21336785 )
2011
11
The effect of HSP-causing mutations in SPG3A and NIPA1 on the assembly, trafficking, and interaction between atlastin-1 and NIPA1. ( 20816793 )
2011
12
Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1/SPG3A. ( 21220294 )
2011
13
Hereditary spastic paraplegia and axonal motor neuropathy caused by a novel SPG3A de novo mutation. ( 19735987 )
2010
14
Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia. ( 20932283 )
2010
15
Complex phenotype in an Italian family with a novel mutation in SPG3A. ( 19768483 )
2010
16
Four novel SPG3A/atlastin mutations identified in autosomal dominant hereditary spastic paraplegia kindreds with intra-familial variability in age of onset and complex phenotype. ( 19459885 )
2009
17
Hereditary spastic paraplegia: identification of an SPG3A gene mutation in a Chinese family. ( 19652243 )
2009
18
Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia. ( 19423133 )
2009
19
Atlastin-1, the dynamin-like GTPase responsible for spastic paraplegia SPG3A, remodels lipid membranes and may form tubules and vesicles in the endoplasmic reticulum. ( 19573020 )
2009
20
Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families. ( 18664244 )
2009
21
Novel SPG3A and SPG4 mutations in two patients with Silver syndrome. ( 19730024 )
2009
22
Normal dopaminergic nigrostriatal innervation in SPG3A hereditary spastic paraplegia. ( 19085270 )
2008
23
Extending the clinical spectrum of SPG3A mutations to a very severe and very early complicated phenotype. ( 18446315 )
2008
24
Hereditary spastic paraplegia 3A associated with axonal neuropathy. ( 17502470 )
2007
25
A novel mutation in the SPG3A gene (atlastin) in hereditary spastic paraplegia. ( 17380240 )
2007
26
A SPG3A mutation with a novel foot phenotype of hereditary spastic paraplegia in a Chinese Han family. ( 17531128 )
2007
27
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
28
Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis. ( 17321752 )
2007
29
Characterization of a novel SPG3A deletion in a French-Canadian family. ( 17427918 )
2007
30
SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years. ( 16401858 )
2006
31
De novo occurrence of novel SPG3A/atlastin mutation presenting as cerebral palsy. ( 16533974 )
2006
32
SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development. ( 16537571 )
2006
33
A founder effect and mutational hot spots may contribute to the most frequent mutations in the SPG3A gene. ( 16612642 )
2006
34
The R495W mutation in SPG3A causes spastic paraplegia associated with axonal neuropathy. ( 15742100 )
2005
35
Mutation analysis of SPG4 and SPG3A genes and its implication in molecular diagnosis of Korean patients with hereditary spastic paraplegia. ( 16009769 )
2005
36
Novel mutations in the Atlastin gene (SPG3A) in families with autosomal dominant hereditary spastic paraplegia and evidence for late onset forms of HSP linked to the SPG3A locus. ( 14695538 )
2004
37
Novel mutation in the SPG3A gene in an African American family with an early onset of hereditary spastic paraplegia. ( 15477516 )
2004
38
Early onset autosomal dominant spastic paraplegia caused by novel mutations in SPG3A. ( 15517445 )
2004
39
Incomplete penetrance in an SPG3A-linked family with a new mutation in the atlastin gene. ( 15184642 )
2004
40
Cellular localization, oligomerization, and membrane association of the hereditary spastic paraplegia 3A (SPG3A) protein atlastin. ( 14506257 )
2003
41
SPG3A mutation screening in English families with early onset autosomal dominant hereditary spastic paraplegia. ( 14607301 )
2003
42
Further evidence that SPG3A gene mutations cause autosomal dominant hereditary spastic paraplegia. ( 12112092 )
2002
43
SPG3A: An additional family carrying a new atlastin mutation. ( 12499504 )
2002

Variations for Spastic Paraplegia 3, Autosomal Dominant

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 3, Autosomal Dominant:

76 (show all 17)
# Symbol AA change Variation ID SNP ID
1 ATL1 p.Arg217Gln VAR_017146 rs119476049
2 ATL1 p.Arg239Cys VAR_017147 rs119476046
3 ATL1 p.His258Arg VAR_017148 rs119476048
4 ATL1 p.Ser259Tyr VAR_017149 rs119476047
5 ATL1 p.Ala161Pro VAR_019446
6 ATL1 p.His247Pro VAR_019447
7 ATL1 p.Leu157Trp VAR_065509 rs119476051
8 ATL1 p.Met408Val VAR_065511 rs28939094
9 ATL1 p.Arg415Trp VAR_065512 rs119476050
10 ATL1 p.Gln154Glu VAR_067655
11 ATL1 p.Val253Ile VAR_067657 rs864622520
12 ATL1 p.Phe413Val VAR_067658
13 ATL1 p.Asn440Thr VAR_067659
14 ATL1 p.Arg495Trp VAR_067660 rs864622269
15 ATL1 p.Arg415Gln VAR_071708 rs397514712
16 ATL1 p.Arg416Cys VAR_071709 rs387906941
17 ATL1 p.Arg118Gln VAR_071874 rs606231265

ClinVar genetic disease variations for Spastic Paraplegia 3, Autosomal Dominant:

6 (show top 50) (show all 132)
# Gene Variation Type Significance SNP ID Assembly Location
1 ATL1 NM_015915.4(ATL1): c.715C> T (p.Arg239Cys) single nucleotide variant Pathogenic rs119476046 GRCh37 Chromosome 14, 51080061: 51080061
2 ATL1 NM_015915.4(ATL1): c.715C> T (p.Arg239Cys) single nucleotide variant Pathogenic rs119476046 GRCh38 Chromosome 14, 50613343: 50613343
3 ATL1 NM_001127713.1(ATL1): c.776C> A (p.Ser259Tyr) single nucleotide variant Pathogenic rs119476047 GRCh37 Chromosome 14, 51081143: 51081143
4 ATL1 NM_001127713.1(ATL1): c.776C> A (p.Ser259Tyr) single nucleotide variant Pathogenic rs119476047 GRCh38 Chromosome 14, 50614425: 50614425
5 ATL1 NM_015915.4(ATL1): c.773A> G (p.His258Arg) single nucleotide variant Pathogenic rs119476048 GRCh37 Chromosome 14, 51081140: 51081140
6 ATL1 NM_015915.4(ATL1): c.773A> G (p.His258Arg) single nucleotide variant Pathogenic rs119476048 GRCh38 Chromosome 14, 50614422: 50614422
7 ATL1 NM_015915.4(ATL1): c.650G> A (p.Arg217Gln) single nucleotide variant Likely pathogenic rs119476049 GRCh37 Chromosome 14, 51079996: 51079996
8 ATL1 NM_015915.4(ATL1): c.650G> A (p.Arg217Gln) single nucleotide variant Likely pathogenic rs119476049 GRCh38 Chromosome 14, 50613278: 50613278
9 ATL1 ATL1, 1-BP INS, 1688A insertion Pathogenic
10 ATL1 NM_015915.4(ATL1): c.1222A> G (p.Met408Val) single nucleotide variant Pathogenic rs28939094 GRCh37 Chromosome 14, 51094851: 51094851
11 ATL1 NM_015915.4(ATL1): c.1222A> G (p.Met408Val) single nucleotide variant Pathogenic rs28939094 GRCh38 Chromosome 14, 50628133: 50628133
12 ATL1 NM_015915.4(ATL1): c.1243C> T (p.Arg415Trp) single nucleotide variant Pathogenic/Likely pathogenic rs119476050 GRCh37 Chromosome 14, 51094872: 51094872
13 ATL1 NM_015915.4(ATL1): c.1243C> T (p.Arg415Trp) single nucleotide variant Pathogenic/Likely pathogenic rs119476050 GRCh38 Chromosome 14, 50628154: 50628154
14 ATL1 NM_001127713.1(ATL1): c.470T> G (p.Leu157Trp) single nucleotide variant Pathogenic rs119476051 GRCh37 Chromosome 14, 51058305: 51058305
15 ATL1 NM_001127713.1(ATL1): c.470T> G (p.Leu157Trp) single nucleotide variant Pathogenic rs119476051 GRCh38 Chromosome 14, 50591587: 50591587
16 ATL1 ATL1, 3-BP DEL deletion Pathogenic
17 ATL1 NM_001127713.1(ATL1): c.1519dupA (Ile507Asnfs) duplication Pathogenic rs863223314 GRCh37 Chromosome 14, 51095148: 51095148
18 ATL1 NM_001127713.1(ATL1): c.1519dupA (Ile507Asnfs) duplication Pathogenic rs863223314 GRCh38 Chromosome 14, 50628430: 50628430
19 ATL1 NM_015915.4(ATL1): c.129C> G (p.Asp43Glu) single nucleotide variant Benign rs17850684 GRCh37 Chromosome 14, 51054643: 51054643
20 ATL1 NM_015915.4(ATL1): c.129C> G (p.Asp43Glu) single nucleotide variant Benign rs17850684 GRCh38 Chromosome 14, 50587925: 50587925
21 ATL1 NM_015915.4(ATL1): c.351G> A (p.Glu117=) single nucleotide variant Benign rs1060197 GRCh37 Chromosome 14, 51057727: 51057727
22 ATL1 NM_015915.4(ATL1): c.351G> A (p.Glu117=) single nucleotide variant Benign rs1060197 GRCh38 Chromosome 14, 50591009: 50591009
23 ATL1 NM_015915.4(ATL1): c.467C> T (p.Thr156Ile) single nucleotide variant Pathogenic rs137852657 GRCh37 Chromosome 14, 51058302: 51058302
24 ATL1 NM_015915.4(ATL1): c.467C> T (p.Thr156Ile) single nucleotide variant Pathogenic rs137852657 GRCh38 Chromosome 14, 50591584: 50591584
25 ATL1 NM_015915.4(ATL1): c.578T> G (p.Phe193Cys) single nucleotide variant Benign rs17850683 GRCh37 Chromosome 14, 51062298: 51062298
26 ATL1 NM_015915.4(ATL1): c.578T> G (p.Phe193Cys) single nucleotide variant Benign rs17850683 GRCh38 Chromosome 14, 50595580: 50595580
27 ATL1 NM_015915.4(ATL1): c.621G> A (p.Lys207=) single nucleotide variant Benign/Likely benign rs35629585 GRCh37 Chromosome 14, 51062341: 51062341
28 ATL1 NM_015915.4(ATL1): c.621G> A (p.Lys207=) single nucleotide variant Benign/Likely benign rs35629585 GRCh38 Chromosome 14, 50595623: 50595623
29 ATL1 NM_015915.4(ATL1): c.84A> G (p.Pro28=) single nucleotide variant Benign rs35014209 GRCh37 Chromosome 14, 51054598: 51054598
30 ATL1 NM_015915.4(ATL1): c.84A> G (p.Pro28=) single nucleotide variant Benign rs35014209 GRCh38 Chromosome 14, 50587880: 50587880
31 ATL1 NM_015915.4(ATL1): c.196G> C (p.Glu66Gln) single nucleotide variant Uncertain significance rs200314808 GRCh37 Chromosome 14, 51054710: 51054710
32 ATL1 NM_015915.4(ATL1): c.196G> C (p.Glu66Gln) single nucleotide variant Uncertain significance rs200314808 GRCh38 Chromosome 14, 50587992: 50587992
33 ATL1 NM_001127713.1(ATL1): c.1246C> T (p.Arg416Cys) single nucleotide variant Pathogenic rs387906941 GRCh37 Chromosome 14, 51094875: 51094875
34 ATL1 NM_001127713.1(ATL1): c.1246C> T (p.Arg416Cys) single nucleotide variant Pathogenic rs387906941 GRCh38 Chromosome 14, 50628157: 50628157
35 ATL1 NM_015915.4(ATL1): c.1244G> A (p.Arg415Gln) single nucleotide variant Likely pathogenic rs397514712 GRCh37 Chromosome 14, 51094873: 51094873
36 ATL1 NM_015915.4(ATL1): c.1244G> A (p.Arg415Gln) single nucleotide variant Likely pathogenic rs397514712 GRCh38 Chromosome 14, 50628155: 50628155
37 ATL1 NM_015915.4(ATL1): c.630+7G> A single nucleotide variant Benign rs3759588 GRCh37 Chromosome 14, 51062357: 51062357
38 ATL1 NM_015915.4(ATL1): c.630+7G> A single nucleotide variant Benign rs3759588 GRCh38 Chromosome 14, 50595639: 50595639
39 ATL1 NM_001127713.1(ATL1): c.596T> A (p.Leu199Gln) single nucleotide variant Pathogenic rs797045004 GRCh38 Chromosome 14, 50595598: 50595598
40 ATL1 NM_001127713.1(ATL1): c.596T> A (p.Leu199Gln) single nucleotide variant Pathogenic rs797045004 GRCh37 Chromosome 14, 51062316: 51062316
41 ATL1 NM_015915.4(ATL1): c.300T> G (p.Val100=) single nucleotide variant Uncertain significance rs863224772 GRCh38 Chromosome 14, 50590958: 50590958
42 ATL1 NM_015915.4(ATL1): c.300T> G (p.Val100=) single nucleotide variant Uncertain significance rs863224772 GRCh37 Chromosome 14, 51057676: 51057676
43 ATL1 NM_015915.4(ATL1): c.1641G> A (p.Ser547=) single nucleotide variant Likely benign rs761099386 GRCh38 Chromosome 14, 50632303: 50632303
44 ATL1 NM_015915.4(ATL1): c.1641G> A (p.Ser547=) single nucleotide variant Likely benign rs761099386 GRCh37 Chromosome 14, 51099021: 51099021
45 ATL1 NM_015915.4(ATL1): c.1193C> A (p.Ser398Tyr) single nucleotide variant Likely pathogenic rs864622083 GRCh37 Chromosome 14, 51094822: 51094822
46 ATL1 NM_015915.4(ATL1): c.1483C> T (p.Arg495Trp) single nucleotide variant Pathogenic/Likely pathogenic rs864622269 GRCh37 Chromosome 14, 51095112: 51095112
47 ATL1 NM_015915.4(ATL1): c.757G> A (p.Val253Ile) single nucleotide variant Pathogenic/Likely pathogenic rs864622520 GRCh37 Chromosome 14, 51081124: 51081124
48 ATL1 NM_015915.4(ATL1): c.757G> A (p.Val253Ile) single nucleotide variant Pathogenic/Likely pathogenic rs864622520 GRCh38 Chromosome 14, 50614406: 50614406
49 ATL1 NM_015915.4(ATL1): c.1193C> A (p.Ser398Tyr) single nucleotide variant Likely pathogenic rs864622083 GRCh38 Chromosome 14, 50628104: 50628104
50 ATL1 NM_015915.4(ATL1): c.1483C> T (p.Arg495Trp) single nucleotide variant Pathogenic/Likely pathogenic rs864622269 GRCh38 Chromosome 14, 50628394: 50628394

Expression for Spastic Paraplegia 3, Autosomal Dominant

Search GEO for disease gene expression data for Spastic Paraplegia 3, Autosomal Dominant.

Pathways for Spastic Paraplegia 3, Autosomal Dominant

GO Terms for Spastic Paraplegia 3, Autosomal Dominant

Cellular components related to Spastic Paraplegia 3, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.96 ATL1 CDH1 CDH3 CDH5 NIPA1 PECAM1
2 endoplasmic reticulum tubular network GO:0071782 9.16 ATL1 REEP1
3 cell-cell adherens junction GO:0005913 9.13 CDH1 CDH3 CDH5
4 catenin complex GO:0016342 8.8 CDH1 CDH3 CDH5

Biological processes related to Spastic Paraplegia 3, Autosomal Dominant according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.8 CDH1 CDH3 CDH5 FN1 PECAM1
2 extracellular matrix organization GO:0030198 9.67 CDH1 FN1 PECAM1
3 cell-cell adhesion GO:0098609 9.61 CDH1 CDH3 CDH5
4 calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules GO:0016339 9.54 CDH1 CDH3 CDH5
5 mesoderm development GO:0007498 9.51 SNAI1 TBX1
6 cell-cell junction assembly GO:0007043 9.5 CDH1 CDH3 CDH5
7 embryonic cranial skeleton morphogenesis GO:0048701 9.48 SMAD2 TBX1
8 mesoderm formation GO:0001707 9.46 SMAD2 SNAI1
9 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007156 9.46 CDH1 CDH3 CDH5 PECAM1
10 adherens junction organization GO:0034332 9.43 CDH1 CDH3 CDH5
11 cell-cell adhesion mediated by cadherin GO:0044331 9.13 CDH1 CDH3 CDH5
12 wound healing GO:0042060 8.92 CDH3 FN1 PECAM1 SMAD2

Molecular functions related to Spastic Paraplegia 3, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 disordered domain specific binding GO:0097718 9.16 FN1 SMAD2
2 cytoskeletal protein binding GO:0008092 9.13 CDH1 CDH3 CDH5
3 protein homodimerization activity GO:0042803 9.1 CDH1 CDH3 CDH5 PECAM1 SMAD2 TBX1

Sources for Spastic Paraplegia 3, Autosomal Dominant

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