SPG76
MCID: SPS210
MIFTS: 37

Spastic Paraplegia 76, Autosomal Recessive (SPG76)

Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Spastic Paraplegia 76, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 76, Autosomal Recessive:

Name: Spastic Paraplegia 76, Autosomal Recessive 57 72 29 6
Spg76 57 12 58 72
Autosomal Recessive Spastic Paraplegia Type 76 58 17
Hereditary Spastic Paraplegia 76 12 15
Paraplegia, Spastic, Autosomal Recessive, Type 76 39
Autosomal Recessive Spastic Paraplegia 76 12

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
average age at onset 28.5 years (range 19 to 39)
three families have been reported (last curated may 2016)


HPO:

31
spastic paraplegia 76, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spastic Paraplegia 76, Autosomal Recessive

UniProtKB/Swiss-Prot : 72 Spastic paraplegia 76, 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.

MalaCards based summary : Spastic Paraplegia 76, Autosomal Recessive, also known as spg76, is related to paraplegia and hereditary spastic paraplegia. An important gene associated with Spastic Paraplegia 76, Autosomal Recessive is CAPN1 (Calpain 1). Affiliated tissues include skeletal muscle and eye, and related phenotypes are babinski sign and lower limb spasticity

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the CAPN1 gene on chromosome 11q13.

OMIM® : 57 Spastic paraplegia-76 is an autosomal recessive neurologic disorder characterized by young-adult onset of slowly progressive spasticity of the lower limbs resulting in gait difficulties. Most affected individuals have upper limb involvement and additional features such as foot deformities and dysarthria. Cognition is unaffected (summary by Gan-Or et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). (616907) (Updated 05-Apr-2021)

Related Diseases for Spastic Paraplegia 76, 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 Dominant
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
Spastic Paraplegia 81, Autosomal Recessive Spastic Paraplegia 82, Autosomal Recessive
Spastic Paraplegia 83, Autosomal Recessive Hereditary Spastic Paraplegia 23
Hereditary Spastic Paraplegia 30 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 76, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 25)
# Related Disease Score Top Affiliating Genes
1 paraplegia 29.2 SPG11 GBA2 CAPN1 ATP13A2
2 hereditary spastic paraplegia 28.8 SPG11 KIF1C GBA2 CAPN1 ATP13A2
3 spastic paraplegia 54, autosomal recessive 10.0 SPG11 GBA2
4 cerebellar ataxia type 47 10.0 PLD3 FAT2
5 spastic paraplegia 43, autosomal recessive 10.0 SPG11 GBA2
6 spastic paraplegia 26, autosomal recessive 10.0 SPG11 GBA2
7 spastic paraplegia 39, autosomal recessive 9.9 SPG11 GBA2
8 hereditary spastic paraplegia 30 9.9 SPG11 KIF1C
9 autosomal recessive cerebellar ataxia 9.9 UBA5 GBA2
10 hereditary spastic paraplegia 23 9.9 SPG11 KIF1C
11 spastic paraplegia 15, autosomal recessive 9.9 SPG11 GBA2
12 spastic paraplegia 45, autosomal recessive 9.9 SPG11 KIF1C
13 spastic paraplegia 56, autosomal recessive 9.9 SPG11 GBA2
14 spastic paraplegia 73, autosomal dominant 9.9 UBA5 KIF1C GBA2
15 spastic paraplegia 46, autosomal recessive 9.8 SPG11 KIF1C GBA2
16 spastic paraparesis 9.8 SPG11 KIF1C GBA2
17 sphingolipidosis 9.7 GBA2 ATP13A2
18 complex hereditary spastic paraplegia 9.7 SPG11 ATP13A2
19 parkinson disease 15, autosomal recessive early-onset 9.7 SPG11 ATP13A2
20 spastic paraplegia 35, autosomal recessive 9.7 SPG11 ATP13A2
21 spastic ataxia 9.6 SPG11 KIF1C GBA2 CAPN1
22 gaucher's disease 9.6 GBA2 ATP13A2
23 neurodegeneration with brain iron accumulation 9.5 SPG11 ATP13A2
24 spinocerebellar ataxia, autosomal recessive 21 9.3 UBA5 PLD3 KIF1C GBA2 FAT2
25 spinocerebellar ataxia, autosomal recessive 24 8.7 UBA5 PLD3 KIF1C GBA2 FAT2 CAPN1

Graphical network of the top 20 diseases related to Spastic Paraplegia 76, Autosomal Recessive:



Diseases related to Spastic Paraplegia 76, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 76, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 76, Autosomal Recessive:

58 31 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 58 31 very rare (1%) Very frequent (99-80%) HP:0003487
2 lower limb spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0002061
3 lower limb hyperreflexia 58 31 very rare (1%) Very frequent (99-80%) HP:0002395
4 dysarthria 58 31 very rare (1%) Frequent (79-30%) HP:0001260
5 skeletal muscle atrophy 58 31 very rare (1%) Frequent (79-30%) HP:0003202
6 pes cavus 58 31 very rare (1%) Frequent (79-30%) HP:0001761
7 peripheral neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0009830
8 gait ataxia 58 31 very rare (1%) Frequent (79-30%) HP:0002066
9 lower limb muscle weakness 58 31 very rare (1%) Frequent (79-30%) HP:0007340
10 hyperreflexia in upper limbs 58 31 very rare (1%) Frequent (79-30%) HP:0007350
11 scoliosis 58 31 very rare (1%) Occasional (29-5%) HP:0002650
12 abnormality of eye movement 58 31 occasional (7.5%) Occasional (29-5%) HP:0000496
13 ankle clonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0011448
14 limb ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002070
15 functional abnormality of the bladder 58 31 occasional (7.5%) Occasional (29-5%) HP:0000009
16 pes valgus 58 31 very rare (1%) Occasional (29-5%) HP:0008081
17 nystagmus 31 very rare (1%) HP:0000639
18 dysmetria 31 very rare (1%) HP:0001310
19 spastic paraplegia 31 very rare (1%) HP:0001258
20 difficulty walking 31 very rare (1%) HP:0002355
21 distal sensory impairment 31 very rare (1%) HP:0002936
22 urinary incontinence 31 very rare (1%) HP:0000020
23 sensory axonal neuropathy 31 very rare (1%) HP:0003390
24 ataxia 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
hyperreflexia
dysarthria
extensor plantar responses
ataxia (in some patients)
dysmetria (in some patients)
more
Neurologic Peripheral Nervous System:
distal sensory impairment (in some patients)
sensory axonal neuropathy (in some patients)

Genitourinary Bladder:
abnormal bladder function (in some patients)

Skeletal Feet:
pes cavus
pes valgus

Head And Neck Eyes:
nystagmus (1 patient)

Clinical features from OMIM®:

616907 (Updated 05-Apr-2021)

Drugs & Therapeutics for Spastic Paraplegia 76, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 76, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 76, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 76, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 76, Autosomal Recessive 29 CAPN1

Anatomical Context for Spastic Paraplegia 76, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 76, Autosomal Recessive:

40
Skeletal Muscle, Eye

Publications for Spastic Paraplegia 76, Autosomal Recessive

Articles related to Spastic Paraplegia 76, Autosomal Recessive:

(show all 12)
# Title Authors PMID Year
1
Mutations in CAPN1 Cause Autosomal-Recessive Hereditary Spastic Paraplegia. 61 6 57
27153400 2016
2
Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations. 6 61
33486633 2021
3
First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery. 6
32214227 2020
4
Novel CAPN1 mutations extend the phenotypic heterogeneity in combined spastic paraplegia and ataxia. 61
32860341 2020
5
CAPN1 and hereditary spastic paraplegia: a novel variant in an Iranian family and overview of the genotype-phenotype correlation. 61
32352326 2020
6
Mutation analysis of CAPN1 in Chinese populations with spastic paraplegia and related neurodegenerative diseases. 61
31982778 2020
7
CAPN1 mutations: Expanding the CAPN1-related phenotype: From hereditary spastic paraparesis to spastic ataxia. 61
30572172 2019
8
SPG76: An extremely rare hereditary spastic paraplegia with a new expanding complicated phenotype. 61
31147273 2019
9
Two novel homozygous mutations of CAPN1 in Chinese patients with hereditary spastic paraplegia and literatures review. 61
31023339 2019
10
Generation of an integration-free induced pluripotent stem cell line, FJMUi001-A, from a hereditary spastic paraplegia patient carrying compound heterozygous p.P498L and p.R618W mutations in CAPN1 (SPG76). 61
30611022 2019
11
A Novel CAPN1 Mutation Causes a Pure Hereditary Spastic Paraplegia in an Italian Family. 61
31231303 2019
12
Hereditary ataxias and paraparesias: clinical and genetic update. 61
29847346 2018

Variations for Spastic Paraplegia 76, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 76, Autosomal Recessive:

6 (show all 20)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CAPN1 NM_005186.4(CAPN1):c.338-1G>A SNV Pathogenic 617483 rs1590847310 GRCh37: 11:64950944-64950944
GRCh38: 11:65183473-65183473
2 CAPN1 NM_005186.4(CAPN1):c.1176G>A (p.Trp392Ter) SNV Pathogenic 802687 rs756830713 GRCh37: 11:64972164-64972164
GRCh38: 11:65204693-65204693
3 CAPN1 NM_005186.4(CAPN1):c.254G>A (p.Trp85Ter) SNV Pathogenic 986744 GRCh37: 11:64950426-64950426
GRCh38: 11:65182955-65182955
4 CAPN1 NM_005186.4(CAPN1):c.623G>A (p.Gly208Asp) SNV Pathogenic 986745 GRCh37: 11:64953673-64953673
GRCh38: 11:65186202-65186202
5 CAPN1 NM_005186.4(CAPN1):c.1005G>A (p.Trp335Ter) SNV Pathogenic 986746 GRCh37: 11:64956057-64956057
GRCh38: 11:65188586-65188586
6 CAPN1 NM_005186.4(CAPN1):c.1129_1133del (p.Arg377fs) Deletion Pathogenic 986747 GRCh37: 11:64956179-64956183
GRCh38: 11:65188708-65188712
7 CAPN1 NM_005186.4(CAPN1):c.1165+1G>A SNV Pathogenic 986748 GRCh37: 11:64956218-64956218
GRCh38: 11:65188747-65188747
8 CAPN1 NM_005186.4(CAPN1):c.1341G>C (p.Glu447Asp) SNV Pathogenic 986749 GRCh37: 11:64972329-64972329
GRCh38: 11:65204858-65204858
9 CAPN1 NM_005186.4(CAPN1):c.1418_1419del (p.Arg473fs) Microsatellite Pathogenic 986750 GRCh37: 11:64973994-64973995
GRCh38: 11:65206523-65206524
10 CAPN1 NM_005186.4(CAPN1):c.1697dup (p.Leu566fs) Duplication Pathogenic 986751 GRCh37: 11:64975699-64975700
GRCh38: 11:65208228-65208229
11 CAPN1 NM_005186.4(CAPN1):c.1969G>T (p.Glu657Ter) SNV Pathogenic 986752 GRCh37: 11:64977833-64977833
GRCh38: 11:65210362-65210362
12 CAPN1 NM_005186.4(CAPN1):c.1153C>T (p.Arg385Ter) SNV Pathogenic 489122 rs955142329 GRCh37: 11:64956205-64956205
GRCh38: 11:65188734-65188734
13 CAPN1 NM_005186.4(CAPN1):c.1579C>T (p.Gln527Ter) SNV Pathogenic 225766 rs875989787 GRCh37: 11:64974264-64974264
GRCh38: 11:65206793-65206793
14 CAPN1 NM_005186.4(CAPN1):c.407del (p.Pro136fs) Deletion Pathogenic 225767 rs875989845 GRCh37: 11:64951013-64951013
GRCh38: 11:65183542-65183542
15 CAPN1 NM_005186.4(CAPN1):c.884G>C (p.Arg295Pro) SNV Pathogenic 225765 rs756205995 GRCh37: 11:64955466-64955466
GRCh38: 11:65187995-65187995
16 CAPN1 NM_005186.4(CAPN1):c.618_619del (p.Gly208fs) Deletion Pathogenic 802686 rs778722037 GRCh37: 11:64953668-64953669
GRCh38: 11:65186197-65186198
17 CAPN1 NM_005186.4(CAPN1):c.1605+5G>A SNV Pathogenic/Likely pathogenic 225768 rs375817528 GRCh37: 11:64974295-64974295
GRCh38: 11:65206824-65206824
18 CAPN1 NM_005186.4(CAPN1):c.929+2T>A SNV Likely pathogenic 1029241 GRCh37: 11:64955513-64955513
GRCh38: 11:65188042-65188042
19 CAPN1 NM_005186.4(CAPN1):c.1015C>T (p.Arg339Ter) SNV Likely pathogenic 974855 GRCh37: 11:64956067-64956067
GRCh38: 11:65188596-65188596
20 CAPN1 NM_005186.4(CAPN1):c.1442G>A (p.Arg481Gln) SNV Uncertain significance 584446 rs763471308 GRCh37: 11:64974022-64974022
GRCh38: 11:65206551-65206551

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 76, Autosomal Recessive:

72
# Symbol AA change Variation ID SNP ID
1 CAPN1 p.Arg295Pro VAR_077899 rs756205995

Expression for Spastic Paraplegia 76, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 76, Autosomal Recessive.

Pathways for Spastic Paraplegia 76, Autosomal Recessive

GO Terms for Spastic Paraplegia 76, Autosomal Recessive

Cellular components related to Spastic Paraplegia 76, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.33 PLD3 CAPN1 ATP13A2
2 lysosomal lumen GO:0043202 9.26 PLD3 ATP13A2
3 lysosomal membrane GO:0005765 9.13 SPG11 PLD3 ATP13A2
4 Golgi apparatus GO:0005794 9.02 UBA5 PLD3 KIF1C GBA2 FAT2

Biological processes related to Spastic Paraplegia 76, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of macroautophagy GO:0016241 8.62 CAPN1 ATP13A2

Sources for Spastic Paraplegia 76, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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