SPG43
MCID: SPS130
MIFTS: 37

Spastic Paraplegia 43, Autosomal Recessive (SPG43)

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Aliases & Classifications for Spastic Paraplegia 43, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 43, Autosomal Recessive:

Name: Spastic Paraplegia 43, Autosomal Recessive 56 73 29 13 6 71
Spg43 56 12 58 73
Autosomal Recessive Spastic Paraplegia Type 43 12 58
Hereditary Spastic Paraplegia 43 12 15
Paraplegia, Spastic, Type 43, Autosomal Recessive 39
Autosomal Recessive Spastic Paraplegia 43 12

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive spastic paraplegia type 43
Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
slowly progressive
onset in first decade
one family of mali origin has been reported (last curated january 2013)


HPO:

31
spastic paraplegia 43, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110795
OMIM 56 615043
OMIM Phenotypic Series 56 PS303350
MeSH 43 D015419
ICD10 32 G11.4
ICD10 via Orphanet 33 G11.4
Orphanet 58 ORPHA320370
UMLS 71 C2680446

Summaries for Spastic Paraplegia 43, Autosomal Recessive

UniProtKB/Swiss-Prot : 73 Spastic paraplegia 43, autosomal recessive: 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. SP43 is characterized by childhood onset of progressive spasticity affecting the lower and upper limbs.

MalaCards based summary : Spastic Paraplegia 43, Autosomal Recessive, also known as spg43, is related to neurodegeneration with brain iron accumulation 4 and neurodegeneration with brain iron accumulation, and has symptoms including muscle spasticity An important gene associated with Spastic Paraplegia 43, Autosomal Recessive is C19orf12 (Chromosome 19 Open Reading Frame 12). Related phenotypes are babinski sign and poor fine motor coordination

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the C19ORF12 gene on chromosome 19q12.

OMIM : 56 Spastic paraplegia-43 (SPG43) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive spasticity affecting the lower and upper limbs (summary by Meilleur et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800. (615043)

Related Diseases for Spastic Paraplegia 43, Autosomal Recessive

Diseases in the Spastic Paraplegia 3a family:

Spastic Paraplegia 3, Autosomal Dominant Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 17, Autosomal Dominant Spastic Paraplegia 15, Autosomal Recessive
Spastic Paraplegia 23, Autosomal Recessive Spastic Paraplegia 5a, Autosomal Recessive
Spastic Paraplegia 20, Autosomal Recessive Spastic Paraplegia 6, Autosomal Dominant
Spastic Paraplegia 9a, Autosomal Dominant Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 10, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 12, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 13, Autosomal Dominant Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 7, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 25, Autosomal Recessive Spastic Paraplegia 27, Autosomal Recessive
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 29, Autosomal Dominant Spastic Paraplegia 33, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 30, Autosomal Recessive
Spastic Paraplegia 18, Autosomal Recessive Spastic Paraplegia 32, Autosomal Recessive
Spastic Paraplegia 37, Autosomal Dominant Spastic Paraplegia 39, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 38, Autosomal Dominant
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 36, Autosomal Dominant Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 44, Autosomal Recessive Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 51, Autosomal Recessive
Spastic Paraplegia 47, Autosomal Recessive Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 53, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 55, Autosomal Recessive
Spastic Paraplegia 43, Autosomal Recessive Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 72, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 62, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 61, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive
Spastic Paraplegia 73, Autosomal Dominant Spastic Paraplegia 74, Autosomal Recessive
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 75, Autosomal Recessive
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 77, Autosomal Recessive
Spastic Paraplegia 78, Autosomal Recessive Spastic Paraplegia 80, Autosomal Dominant
Hereditary Spastic Paraplegia 23 Hereditary Spastic Paraplegia 51
Hereditary Spastic Paraplegia 72 Hereditary Spastic Paraplegia
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 Spastic Paraplegia 10
Spastic Paraplegia 12 Spastic Paraplegia 13
Spastic Paraplegia 14 Spastic Paraplegia 15
Spastic Paraplegia 16 Spastic Paraplegia 17
Spastic Paraplegia 18 Spastic Paraplegia 19
Spastic Paraplegia 24 Spastic Paraplegia 25
Spastic Paraplegia 26 Spastic Paraplegia 29
Spastic Paraplegia 3 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 47
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Spastic Paraplegia Type 49 Autosomal Recessive Spastic Paraplegia Type 60
Autosomal Recessive Spastic Paraplegia Type 59 Autosomal Recessive Spastic Paraplegia Type 69
Autosomal Recessive Spastic Paraplegia Type 70 Autosomal Recessive Spastic Paraplegia Type 71
Autosomal Recessive Spastic Paraplegia Type 66 Autosomal Recessive Spastic Paraplegia Type 67
Autosomal Dominant Spastic Paraplegia Type 9b

Diseases related to Spastic Paraplegia 43, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 79)
# Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 4 30.3 FA2H ERLIN2 C19orf12
2 neurodegeneration with brain iron accumulation 30.0 SPG11 FA2H DDHD1 C19orf12
3 paraplegia 25.6 ZFYVE27 ZFYVE26 VPS37A SPG11 SPAST SLC33A1
4 hereditary spastic paraplegia 25.6 ZFYVE27 ZFYVE26 VPS37A SPG11 SPAST SLC33A1
5 spastic paraplegia 5a 10.4 GBA2 C19orf12
6 neurodegeneration with brain iron accumulation 2b 10.3 FA2H C19orf12
7 pure hereditary spastic paraplegia 10.3 SPAST ERLIN2
8 neuropathy, hereditary sensory, type iic 10.2 SPG11 FA2H
9 juvenile-onset parkinson's disease 10.2 FA2H C19orf12
10 sjogren-larsson syndrome 10.2 FA2H DDHD1
11 juvenile amyotrophic lateral sclerosis 10.2 SPG11 C19orf12
12 neurodegeneration with brain iron accumulation 3 10.2 FA2H C19orf12
13 mitochondrial membrane protein-associated neurodegeneration 10.2
14 neurodegeneration with brain iron accumulation 5 10.2 FA2H C19orf12
15 neurodegeneration with brain iron accumulation 6 10.1 FA2H C19orf12
16 spastic paraplegia 61, autosomal recessive 10.1 SPAST ARL6IP1
17 spastic paraplegia 76, autosomal recessive 10.1 GBA2 FA2H
18 spastic paraplegia 57, autosomal recessive 10.1 SPG11 ERLIN2
19 neurodegeneration with brain iron accumulation 2a 10.1 FA2H C19orf12
20 spinocerebellar ataxia, autosomal recessive 20 10.1 ZFYVE26 SPG11
21 spastic paraplegia 11, autosomal recessive 10.1 ZFYVE26 SPG11
22 neurodegeneration with brain iron accumulation 1 10.1 FA2H C19orf12
23 spastic paraplegia 30, autosomal recessive 10.1 SPG11 SPAST FA2H
24 parkinson disease 15, autosomal recessive early-onset 10.0 SPG11 FA2H C19orf12
25 autosomal dominant non-syndromic intellectual disability 9 10.0 ZFYVE26 VPS37A
26 spastic paraplegia 28, autosomal recessive 10.0 SPG11 FA2H DDHD1
27 kufor-rakeb syndrome 10.0 FA2H C19orf12
28 hereditary spastic paraplegia 72 10.0 ZFYVE26 SPG11 SPAST
29 amyotrophic lateral sclerosis type 5 10.0 ZFYVE26 SPG11 SPAST
30 charcot-marie-tooth disease, axonal, type 2t 10.0 ZFYVE26 GBA2 FA2H
31 spasticity 10.0 SPAST DDHD1
32 spastic paraplegia 17, autosomal dominant 10.0 ZFYVE26 SPG11 SPAST
33 axonal neuropathy 9.9 ZFYVE26 SPG11 C19orf12
34 spastic paraplegia 20, autosomal recessive 9.9 ZFYVE26 SPG11 SPAST
35 spastic paraplegia 49, autosomal recessive 9.9 ZFYVE26 SPG11 DDHD1
36 spastic paraplegia 3, autosomal dominant 9.9 ZFYVE26 SPG11 SPAST
37 spastic paraplegia 55, autosomal recessive 9.9 ZFYVE26 SPG11 DDHD1
38 mast syndrome 9.9 ZFYVE27 SPG11
39 spastic paraplegia 47, autosomal recessive 9.9 ZFYVE26 SPG11 ERLIN2
40 spastic paraplegia 54, autosomal recessive 9.8 SPG11 GBA2 FA2H DDHD1
41 spastic paraplegia 56, autosomal recessive 9.8 SPG11 GBA2 FA2H DDHD1
42 hereditary spastic paraplegia 51 9.8 ZFYVE26 VPS37A SPG11
43 spastic paraplegia 34, x-linked 9.8 ZFYVE26 SLC33A1
44 spastic paraplegia 29, autosomal dominant 9.8 ZFYVE26 SLC33A1
45 neuroaxonal dystrophy 9.8 FA2H C19orf12
46 spastic paraplegia 52, autosomal recessive 9.8 ZFYVE26 VPS37A SPG11
47 spastic paraplegia 37, autosomal dominant 9.8 ZFYVE26 SLC33A1
48 spastic paraplegia 25, autosomal recessive 9.8 ZFYVE26 SLC33A1
49 spastic paraplegia 19, autosomal dominant 9.8 ZFYVE26 SLC33A1
50 spastic paraplegia 35, autosomal recessive 9.7 ZFYVE26 SPG11 FA2H C19orf12

Graphical network of the top 20 diseases related to Spastic Paraplegia 43, Autosomal Recessive:



Diseases related to Spastic Paraplegia 43, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 43, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 43, Autosomal Recessive:

58 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0003487
2 poor fine motor coordination 58 31 hallmark (90%) Very frequent (99-80%) HP:0007010
3 difficulty walking 58 31 hallmark (90%) Very frequent (99-80%) HP:0002355
4 distal amyotrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003693
5 spastic gait 58 31 hallmark (90%) Very frequent (99-80%) HP:0002064
6 distal muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0002460
7 spastic paraparesis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002313
8 generalized hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001290
9 pes cavus 58 31 frequent (33%) Frequent (79-30%) HP:0001761
10 brisk reflexes 58 31 frequent (33%) Frequent (79-30%) HP:0001348
11 knee flexion contracture 58 31 frequent (33%) Frequent (79-30%) HP:0006380
12 flexion contracture of finger 58 31 frequent (33%) Frequent (79-30%) HP:0012785
13 absent achilles reflex 58 31 frequent (33%) Frequent (79-30%) HP:0003438
14 impaired vibratory sensation 58 31 frequent (33%) Frequent (79-30%) HP:0002495
15 hyperactive patellar reflex 58 31 frequent (33%) Frequent (79-30%) HP:0007083
16 ankle flexion contracture 31 frequent (33%) HP:0006466
17 spasticity 58 31 Frequent (79-30%) HP:0001257
18 dysarthria 31 HP:0001260
19 gait disturbance 31 HP:0001288
20 muscle weakness 31 HP:0001324
21 hyperreflexia 31 HP:0001347
22 hyporeflexia 31 HP:0001265
23 spastic paraplegia 31 HP:0001258
24 ankle contracture 58 Frequent (79-30%)
25 distal sensory impairment 31 HP:0002936

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
hyperreflexia
extensor plantar responses
gait difficulties
difficulties in fine movement of the hands
more
Neurologic Peripheral Nervous System:
hyporeflexia
distal sensory impairment

Skeletal Hands:
contractures of the fingers
atrophy of the intrinsic hand muscles

Skeletal Feet:
pes cavus

Skeletal Limbs:
contractures of the ankles
contractures of the knees

Muscle Soft Tissue:
distal muscle atrophy, upper and lower limbs
distal muscle weakness, upper and lower limbs

Clinical features from OMIM:

615043

UMLS symptoms related to Spastic Paraplegia 43, Autosomal Recessive:


muscle spasticity

Drugs & Therapeutics for Spastic Paraplegia 43, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 43, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 43, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 43, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 43, Autosomal Recessive 29 C19orf12

Anatomical Context for Spastic Paraplegia 43, Autosomal Recessive

Publications for Spastic Paraplegia 43, Autosomal Recessive

Articles related to Spastic Paraplegia 43, Autosomal Recessive:

# Title Authors PMID Year
1
Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12. 56 61 6
23857908 2013
2
Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19. 61 6 56
20039086 2010
3
Hereditary Spastic Paraplegia Overview 6
20301682 2000
4
Clinical and genetic spectrum of an orphan disease MPAN: a series with new variants and a novel phenotype. 61
31804703 2019
5
Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia. 61
26714052 2016

Variations for Spastic Paraplegia 43, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 43, Autosomal Recessive:

6 (show all 19) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 C19orf12 NM_001256047.1(C19orf12):c.161G>A (p.Gly54Glu)SNV Pathogenic 617481 rs752450983 19:30193884-30193884 19:29702977-29702977
2 C19orf12 NM_001256047.1(C19orf12):c.172G>A (p.Gly58Arg)SNV Pathogenic/Likely pathogenic 31157 rs515726205 19:30193873-30193873 19:29702966-29702966
3 C19orf12 NM_001256047.1(C19orf12):c.154G>C (p.Ala52Pro)SNV Likely pathogenic 88865 rs376103979 19:30199167-30199167 19:29708260-29708260
4 C19orf12 NM_001256047.1(C19orf12):c.391A>G (p.Lys131Glu)SNV Conflicting interpretations of pathogenicity 31158 rs146170087 19:30193654-30193654 19:29702747-29702747
5 C19orf12 NM_001256047.1(C19orf12):c.216G>A (p.Pro72=)SNV Conflicting interpretations of pathogenicity 238220 rs202054484 19:30193829-30193829 19:29702922-29702922
6 C19orf12 NM_001256047.1(C19orf12):c.69G>A (p.Ala23=)SNV Conflicting interpretations of pathogenicity 238219 rs201118405 19:30199252-30199252 19:29708345-29708345
7 C19orf12 NM_001256047.1(C19orf12):c.313G>A (p.Val105Met)SNV Uncertain significance 286392 rs146492790 19:30193732-30193732 19:29702825-29702825
8 C19orf12 NM_001256047.1(C19orf12):c.68C>T (p.Ala23Val)SNV Uncertain significance 328731 rs544395324 19:30199253-30199253 19:29708346-29708346
9 C19orf12 NM_001256047.1(C19orf12):c.277G>A (p.Ala93Thr)SNV Uncertain significance 661004 19:30193768-30193768 19:29702861-29702861
10 C19orf12 NM_001256047.1(C19orf12):c.-11+661G>ASNV Uncertain significance 642357 19:30205809-30205809 19:29714902-29714902
11 C19orf12 NM_001256047.1(C19orf12):c.270del (p.Asn90fs)deletion Uncertain significance 469658 rs1555714836 19:30193775-30193775 19:29702868-29702868
12 C19orf12 NM_001256047.1(C19orf12):c.121G>A (p.Val41Ile)SNV Uncertain significance 469655 rs148797643 19:30199200-30199200 19:29708293-29708293
13 C19orf12 NM_001256047.1(C19orf12):c.282dup (p.Ile95fs)duplication Uncertain significance 469659 rs1555714827 19:30193763-30193763 19:29702856-29702856
14 C19orf12 NM_001256047.1(C19orf12):c.204A>T (p.Gly68=)SNV Uncertain significance 469656 rs1555714878 19:30193841-30193841 19:29702934-29702934
15 C19orf12 NM_001256047.1(C19orf12):c.170T>C (p.Val57Ala)SNV Uncertain significance 579842 19:30193875-30193875 19:29702968-29702968
16 C19orf12 NM_001256047.1(C19orf12):c.123C>T (p.Val41=)SNV Likely benign 537393 rs374520604 19:30199198-30199198 19:29708291-29708291
17 C19orf12 NM_001256047.1(C19orf12):c.238C>T (p.Leu80=)SNV Likely benign 469657 rs753364652 19:30193807-30193807 19:29702900-29702900
18 C19orf12 NM_001256047.1(C19orf12):c.413A>G (p.Gln138Arg)SNV Likely benign 380881 rs73023451 19:30193632-30193632 19:29702725-29702725
19 C19orf12 NM_001256047.1(C19orf12):c.392A>C (p.Lys131Thr)SNV Benign/Likely benign 128538 rs79915936 19:30193653-30193653 19:29702746-29702746

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 43, Autosomal Recessive:

73
# Symbol AA change Variation ID SNP ID
1 C19orf12 p.Ala63Pro VAR_070668 rs376103979

Expression for Spastic Paraplegia 43, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 43, Autosomal Recessive.

Pathways for Spastic Paraplegia 43, Autosomal Recessive

GO Terms for Spastic Paraplegia 43, Autosomal Recessive

Cellular components related to Spastic Paraplegia 43, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.81 ZFYVE27 VPS37A SPG11 SPAST GBA2 ERLIN2
2 endoplasmic reticulum membrane GO:0005789 9.5 ZFYVE27 SPAST SLC33A1 GBA2 FA2H ERLIN2
3 endoplasmic reticulum GO:0005783 9.23 ZFYVE27 SPAST SLC33A1 GBA2 FA2H ERLIN2

Biological processes related to Spastic Paraplegia 43, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.26 GBA2 FA2H ERLIN2 DDHD1
2 mitotic cytokinesis GO:0000281 9.16 ZFYVE26 SPAST
3 endoplasmic reticulum tubular network formation GO:0071787 8.62 ZFYVE27 ARL6IP1

Sources for Spastic Paraplegia 43, Autosomal Recessive

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