SPG56
MCID: SPS101
MIFTS: 40

Spastic Paraplegia 56, Autosomal Recessive (SPG56)

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 56, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 56, Autosomal Recessive:

Name: Spastic Paraplegia 56, Autosomal Recessive 56 73 29 13 6 71
Spg56 56 12 58 73
Autosomal Recessive Spastic Paraplegia Type 56 12 58
Hereditary Spastic Paraplegia 56 12 15
Paraplegia, Spastic, Type 56, Autosomal Recessive 39
Autosomal Recessive Spastic Paraplegia 56 12

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive spastic paraplegia type 56
Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in the first decade (range birth to 8 years)


HPO:

31
spastic paraplegia 56, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110808
OMIM 56 615030
OMIM Phenotypic Series 56 PS303350
MeSH 43 D015419
ICD10 32 G11.4
ICD10 via Orphanet 33 G11.4
Orphanet 58 ORPHA320411
UMLS 71 C3539507

Summaries for Spastic Paraplegia 56, Autosomal Recessive

UniProtKB/Swiss-Prot : 73 Spastic paraplegia 56, 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. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. In SPG56, upper limbs are often also affected. Some SPG56 patients may have a subclinical axonal neuropathy.

MalaCards based summary : Spastic Paraplegia 56, Autosomal Recessive, also known as spg56, is related to spastic paraplegia 46, autosomal recessive and paraplegia. An important gene associated with Spastic Paraplegia 56, Autosomal Recessive is CYP2U1 (Cytochrome P450 Family 2 Subfamily U Member 1). Affiliated tissues include globus pallidus, eye and bone, and related phenotypes are babinski sign and lower limb hyperreflexia

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the CYP2U1 gene on chromosome 4q25.

OMIM : 56 SPG56 is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive lower-limb spasticity resulting in walking difficulties. Upper limbs are often also affected, and some patients may have a subclinical axonal neuropathy (summary by Tesson et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800. (615030)

Related Diseases for Spastic Paraplegia 56, 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 56, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 73)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 46, autosomal recessive 27.6 SPG21 SPG11 GBA2 FA2H DDHD2 DDHD1
2 paraplegia 26.5 SPG21 SPG11 GBA2 FA2H DDHD2 DDHD1
3 hereditary spastic paraplegia 26.5 SPG21 SPG11 GBA2 FA2H DDHD2 DDHD1
4 charcot-marie-tooth disease, axonal, type 2h 10.3 SPG21 CYP2U1
5 charcot-marie-tooth disease, axonal, type 2r 10.3 SPG21 CYP2U1
6 charcot-marie-tooth disease, axonal, type 2b2 10.3 SPG21 CYP2U1
7 hereditary spastic paraplegia 23 10.3 SPG21 SPG11
8 spastic paraplegia 45, autosomal recessive 10.3 SPG21 DDHD2
9 spastic paraplegia 16, x-linked 10.2 SPG21 SPG11
10 complex hereditary spastic paraplegia 10.2 SPG11 DDHD2
11 spastic paraplegia 64, autosomal recessive 10.2 SPG21 SPG11
12 spastic paraplegia 73, autosomal dominant 10.2 SPG21 GBA2
13 spastic paraplegia 63, autosomal recessive 10.2 SPG21 SPG11
14 hydromyelia 10.2
15 mast syndrome 10.2 SPG21 SPG11
16 spasticity 10.1
17 spastic paraplegia 10, autosomal dominant 10.1 SPG21 SPG11
18 spastic paraplegia 17, autosomal dominant 10.1 SPG21 SPG11
19 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 10.1 DDHD2 DDHD1
20 spastic paraplegia 5a, autosomal recessive 10.1 SPG11 FA2H
21 spastic paraplegia 5a 10.1 LOC101929595 GBA2 CYP2U1
22 spastic paraplegia 20, autosomal recessive 10.0 SPG21 SPG11
23 polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 10.0 DDHD2 DDHD1 CYP2U1
24 spastic paraplegia 76, autosomal recessive 10.0 GBA2 FA2H
25 spastic paraplegia 55, autosomal recessive 9.9 SPG21 SPG11 DDHD1
26 sengers syndrome 9.9 DDHD2 DDHD1
27 ap-4-associated hereditary spastic paraplegia 9.9 AP4S1 AP4B1
28 parkinson disease 15, autosomal recessive early-onset 9.9 SPG11 FA2H
29 spastic paraplegia 51, autosomal recessive 9.9 AP4S1 AP4B1
30 spastic paraplegia 14, autosomal recessive 9.9 SPG21 SPG11 FA2H
31 hypertonia 9.9 AP4S1 AP4B1
32 spastic paraplegia 11, autosomal recessive 9.9 SPG21 SPG11 AP4B1
33 spastic paraplegia 44, autosomal recessive 9.9 SPG21 AP5Z1
34 spastic paraplegia 77, autosomal recessive 9.8 SPG11 GBA2 FA2H
35 amyotrophic lateral sclerosis type 5 9.8 SPG11 AP5Z1
36 spastic paraparesis 9.8 SPG11 FA2H DDHD1
37 spastic paraplegia 42, autosomal dominant 9.8 SPG11 AP5Z1
38 neurodegeneration with brain iron accumulation 9.7 SPG11 FA2H DDHD1
39 spastic paraplegia 13, autosomal dominant 9.7 DDHD1 AP5Z1
40 spastic ataxia 9.7 GBA2 DDHD2
41 autosomal dominant non-syndromic intellectual disability 9 9.7 AP5Z1 AP4S1
42 hereditary spastic paraplegia 72 9.7 SPG21 SPG11 AP5Z1
43 charcot-marie-tooth disease, axonal, type 2t 9.7 SPG21 GBA2 FA2H CYP2U1
44 spastic paraplegia 12, autosomal dominant 9.7 SPG21 SPG11 AP5Z1
45 spastic paraplegia 6, autosomal dominant 9.7 SPG21 SPG11 AP5Z1
46 spastic paraplegia 31, autosomal dominant 9.7 SPG21 SPG11 AP5Z1
47 spastic paraplegia 8, autosomal dominant 9.6 SPG21 SPG11 AP5Z1
48 spastic paraplegia, optic atrophy, and neuropathy 9.6 AP5Z1 AP4S1
49 quadriplegia 9.6 AP4S1 AP4B1
50 sjogren-larsson syndrome 9.6 FA2H DDHD2 DDHD1 CYP2U1

Graphical network of the top 20 diseases related to Spastic Paraplegia 56, Autosomal Recessive:



Diseases related to Spastic Paraplegia 56, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 56, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 56, Autosomal Recessive:

58 31 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0003487
2 lower limb hyperreflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002395
3 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
4 toe walking 58 31 frequent (33%) Frequent (79-30%) HP:0040083
5 spastic gait 58 31 frequent (33%) Frequent (79-30%) HP:0002064
6 unsteady gait 58 31 frequent (33%) Frequent (79-30%) HP:0002317
7 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
8 cognitive impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0100543
9 dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001332
10 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
11 spastic paraplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001258
12 peripheral axonal neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003477
13 abnormal globus pallidus morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0002453
14 basal ganglia calcification 31 occasional (7.5%) HP:0002135
15 motor delay 31 HP:0001270
16 abnormality of the cerebral white matter 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
toe walking
spastic paraplegia
lower limb hyperreflexia
unsteady gait
delayed motor development
more
Neurologic Peripheral Nervous System:
axonal neuropathy, subclinical

Clinical features from OMIM:

615030

Drugs & Therapeutics for Spastic Paraplegia 56, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 56, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 56, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 56, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 56, Autosomal Recessive 29 CYP2U1

Anatomical Context for Spastic Paraplegia 56, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 56, Autosomal Recessive:

40
Globus Pallidus, Eye, Bone, Brain, Skin

Publications for Spastic Paraplegia 56, Autosomal Recessive

Articles related to Spastic Paraplegia 56, Autosomal Recessive:

(show all 16)
# Title Authors PMID Year
1
Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia. 56 6
23176821 2012
2
Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. 56
23176824 2012
3
Hereditary Spastic Paraplegia Overview 6
20301682 2000
4
Rare novel CYP2U1 and ZFYVE26 variants identified in two Pakistani families with spastic paraplegia. 61
32006740 2020
5
Whole exome sequencing identifies novel variant underlying hereditary spastic paraplegia in consanguineous Pakistani families. 61
31281085 2019
6
CYP2U1 activity is altered by missense mutations in hereditary spastic paraplegia 56. 61
29034544 2018
7
An atypical case of SPG56/CYP2U1-related spastic paraplegia presenting with delayed myelination. 61
28725025 2017
8
Long-term follow-up in spastic paraplegia due to SPG56/CYP2U1: age-dependency rather than genetic variability? 61
28120039 2017
9
SPG46 and SPG56 are rare causes of hereditary spastic paraplegia in China. 61
27553021 2016
10
CYP2U1 mutations in two Iranian patients with activity induced dystonia, motor regression and spastic paraplegia. 61
27292318 2016
11
Hereditary spastic paraplegia: Novel mutations and expansion of the phenotype variability in SPG56. 61
26936192 2016
12
Pigmentary degenerative maculopathy as prominent phenotype in an Italian SPG56/CYP2U1 family. 61
26914923 2016
13
Autosomal dominant hereditary spastic paraplegia with axonal sensory motor polyneuropathy maps to chromosome 21q 22.3. 61
26000935 2016
14
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease. 61
26556829 2016
15
Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis. 61
24337409 2014
16
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms. 61
23897027 2013

Variations for Spastic Paraplegia 56, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 56, Autosomal Recessive:

6 (show all 11) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CYP2U1 CYP2U1, 13-BP DEL, NT61deletion Pathogenic 39502
2 CYP2U1 NM_183075.3(CYP2U1):c.947A>T (p.Asp316Val)SNV Pathogenic 39500 rs397514513 4:108866582-108866582 4:107945426-107945426
3 CYP2U1 NM_183075.3(CYP2U1):c.1139A>G (p.Glu380Gly)SNV Pathogenic 39501 rs397514514 4:108868544-108868544 4:107947388-107947388
4 CYP2U1 NM_183075.3(CYP2U1):c.784T>C (p.Cys262Arg)SNV Pathogenic 39503 rs397514515 4:108866419-108866419 4:107945263-107945263
5 CYP2U1 NM_183075.3(CYP2U1):c.943C>T (p.Gln315Ter)SNV Pathogenic 433183 rs1553937522 4:108866578-108866578 4:107945422-107945422
6 CYP2U1 NM_183075.3(CYP2U1):c.1168C>T (p.Arg390Ter)SNV Pathogenic 562229 rs772400670 4:108868573-108868573 4:107947417-107947417
7 CYP2U1 NM_183075.3(CYP2U1):c.1210_1211del (p.Glu404fs)deletion Likely pathogenic 429249 rs767024102 4:108868614-108868615 4:107947458-107947459
8 CYP2U1 NM_183075.3(CYP2U1):c.452C>T (p.Pro151Leu)SNV Likely pathogenic 433182 rs761575210 4:108853251-108853251 4:107932095-107932095
9 CYP2U1 NM_183075.3(CYP2U1):c.739_742del (p.Glu247fs)deletion Likely pathogenic 804444 4:108866371-108866374 4:107945215-107945218
10 CYP2U1 NM_183075.3(CYP2U1):c.1463G>A (p.Arg488Gln)SNV Uncertain significance 635070 rs762873672 4:108871407-108871407 4:107950251-107950251
11 CYP2U1 NM_183075.3(CYP2U1):c.1462C>T (p.Arg488Trp)SNV Uncertain significance 39504 rs141431913 4:108871406-108871406 4:107950250-107950250

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 56, Autosomal Recessive:

73
# Symbol AA change Variation ID SNP ID
1 CYP2U1 p.Cys262Arg VAR_069575 rs397514515
2 CYP2U1 p.Asp316Val VAR_069576 rs397514513
3 CYP2U1 p.Glu380Gly VAR_069577 rs397514514
4 CYP2U1 p.Arg488Trp VAR_069578 rs141431913

Expression for Spastic Paraplegia 56, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 56, Autosomal Recessive.

Pathways for Spastic Paraplegia 56, Autosomal Recessive

GO Terms for Spastic Paraplegia 56, Autosomal Recessive

Cellular components related to Spastic Paraplegia 56, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.55 SPG21 GBA2 DDHD2 AP4S1 AP4B1
2 extrinsic component of membrane GO:0019898 9.26 GBA2 AP4B1
3 endosome lumen GO:0031904 8.96 AP4S1 AP4B1
4 AP-4 adaptor complex GO:0030124 8.62 AP4S1 AP4B1

Biological processes related to Spastic Paraplegia 56, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein targeting GO:0006605 9.26 AP4S1 AP4B1
2 lipid metabolic process GO:0006629 9.26 GBA2 FA2H DDHD2 DDHD1
3 phosphatidic acid biosynthetic process GO:0006654 9.16 DDHD2 DDHD1
4 positive regulation of mitochondrial fission GO:0090141 8.62 DDHD2 DDHD1

Molecular functions related to Spastic Paraplegia 56, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phospholipase activity GO:0004620 8.62 DDHD2 DDHD1

Sources for Spastic Paraplegia 56, Autosomal Recessive

3 CDC
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68 SNOMED-CT via HPO
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