SPG76
MCID: SPS210
MIFTS: 40

Spastic Paraplegia 76, Autosomal Recessive (SPG76)

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 76, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 76, Autosomal Recessive:

Name: Spastic Paraplegia 76, Autosomal Recessive 58 76 30 6
Spg76 58 12 60 76
Autosomal Recessive Spastic Paraplegia Type 76 60 17
Hereditary Spastic Paraplegia 76 12 15
Paraplegia, Spastic, Autosomal Recessive, Type 76 41
Autosomal Recessive Spastic Paraplegia 76 12

Characteristics:

OMIM:

58
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:

33
spastic paraplegia 76, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Spastic Paraplegia 76, Autosomal Recessive

UniProtKB/Swiss-Prot : 76 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 eye and skeletal muscle, 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 : 58 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)

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 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 Hereditary Spastic Paraplegia
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 76, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 paraplegia 29.8 CYP7B1 FA2H PNPLA6 SPG7
2 hereditary spastic paraplegia 28.8 ATP13A2 CAPN1 CYP7B1 FA2H GBA2 KIF1C
3 spastic paraplegia 5a 10.2 CYP7B1 GBA2
4 spastic paraplegia 5a, autosomal recessive 10.2 CYP7B1 PNPLA6
5 spastic paraplegia 43, autosomal recessive 10.2 CYP7B1 PNPLA6
6 sjogren-larsson syndrome 10.1 FA2H PNPLA6
7 spastic paraplegia 24, autosomal recessive 10.1 CYP7B1 SPG7
8 autosomal recessive cerebellar ataxia 10.0 GBA2 SPG7 UBA5
9 spastic paraplegia 15, autosomal recessive 10.0 FA2H SPG7
10 maturity-onset diabetes of the young, type 8, with exocrine dysfunction 9.9 KLF4 SOX2
11 venous hemangioma 9.9 KLF4 SOX2
12 spinocerebellar ataxia 28 9.8 GRM1 SPG7
13 aceruloplasminemia 9.8 ATP13A2 FA2H GBA2 GRM1
14 methylmalonic aciduria, cblb type 9.8 KLF4 SOX2
15 germ cell and embryonal cancer 9.6 KLF4 SOX2
16 spastic paraplegia 73, autosomal dominant 7.8 ATP13A2 CAPN1 CPT1C CYP7B1 FA2H FAT2
17 spinocerebellar ataxia, autosomal recessive 21 7.8 ATP13A2 CAPN1 CPT1C CYP7B1 FA2H FAT2

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:

60 33 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 60 33 very rare (1%) Very frequent (99-80%) HP:0003487
2 lower limb spasticity 60 33 very rare (1%) Very frequent (99-80%) HP:0002061
3 lower limb hyperreflexia 60 33 very rare (1%) Very frequent (99-80%) HP:0002395
4 dysarthria 60 33 very rare (1%) Frequent (79-30%) HP:0001260
5 skeletal muscle atrophy 60 33 very rare (1%) Frequent (79-30%) HP:0003202
6 peripheral neuropathy 60 33 very rare (1%) Frequent (79-30%) HP:0009830
7 gait ataxia 60 33 very rare (1%) Frequent (79-30%) HP:0002066
8 pes cavus 60 33 very rare (1%) Frequent (79-30%) HP:0001761
9 lower limb muscle weakness 60 33 very rare (1%) Frequent (79-30%) HP:0007340
10 hyperreflexia in upper limbs 60 33 very rare (1%) Frequent (79-30%) HP:0007350
11 abnormality of eye movement 60 33 occasional (7.5%) Occasional (29-5%) HP:0000496
12 scoliosis 60 33 very rare (1%) Occasional (29-5%) HP:0002650
13 limb ataxia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002070
14 ankle clonus 60 33 occasional (7.5%) Occasional (29-5%) HP:0011448
15 pes valgus 60 33 occasional (7.5%) Occasional (29-5%) HP:0008081
16 functional abnormality of the bladder 60 33 occasional (7.5%) Occasional (29-5%) HP:0000009
17 nystagmus 33 occasional (7.5%) HP:0000639
18 dysmetria 33 occasional (7.5%) HP:0001310
19 sensory axonal neuropathy 33 occasional (7.5%) HP:0003390
20 distal sensory impairment 33 occasional (7.5%) HP:0002936
21 ataxia 60 Frequent (79-30%)
22 spastic paraplegia 33 HP:0001258

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
dysarthria
hyperreflexia
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

MGI Mouse Phenotypes related to Spastic Paraplegia 76, Autosomal Recessive:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.85 ATP13A2 CPT1C DYSF FA2H GRM1 KLF4
2 homeostasis/metabolism MP:0005376 9.73 CAPN1 CPT1C CYP7B1 DYSF FA2H GBA2
3 immune system MP:0005387 9.17 CAPN1 CPT1C CYP7B1 DYSF KIF1C KLF4

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 30 CAPN1

Anatomical Context for Spastic Paraplegia 76, Autosomal Recessive

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

42
Eye, Skeletal Muscle

Publications for Spastic Paraplegia 76, Autosomal Recessive

Articles related to Spastic Paraplegia 76, Autosomal Recessive:

# Title Authors Year
1
Clinical aspects of hereditary spastic paraplegia 76 and novel CAPN1 mutations. ( 30198554 )
2018
2
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). ( 30611022 )
2018

Variations for Spastic Paraplegia 76, Autosomal Recessive

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

76
# Symbol AA change Variation ID SNP ID
1 CAPN1 p.Arg295Pro VAR_077899 rs756205995

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

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CAPN1 NM_005186.3(CAPN1): c.884G> C (p.Arg295Pro) single nucleotide variant Pathogenic rs756205995 GRCh37 Chromosome 11, 64955466: 64955466
2 CAPN1 NM_005186.3(CAPN1): c.884G> C (p.Arg295Pro) single nucleotide variant Pathogenic rs756205995 GRCh38 Chromosome 11, 65187995: 65187995
3 CAPN1 NM_001198868.1(CAPN1): c.1579C> T (p.Gln527Ter) single nucleotide variant Pathogenic rs875989787 GRCh38 Chromosome 11, 65206793: 65206793
4 CAPN1 NM_001198868.1(CAPN1): c.1579C> T (p.Gln527Ter) single nucleotide variant Pathogenic rs875989787 GRCh37 Chromosome 11, 64974264: 64974264
5 CAPN1 NM_005186.3(CAPN1): c.407delC (p.Pro136Argfs) deletion Pathogenic rs875989845 GRCh38 Chromosome 11, 65183543: 65183543
6 CAPN1 NM_005186.3(CAPN1): c.407delC (p.Pro136Argfs) deletion Pathogenic rs875989845 GRCh37 Chromosome 11, 64951014: 64951014
7 CAPN1 NM_005186.3(CAPN1): c.1605+5G> A single nucleotide variant Likely pathogenic rs375817528 GRCh38 Chromosome 11, 65206824: 65206824
8 CAPN1 NM_005186.3(CAPN1): c.1605+5G> A single nucleotide variant Likely pathogenic rs375817528 GRCh37 Chromosome 11, 64974295: 64974295
9 CAPN1 NM_005186.3(CAPN1): c.1442G> A (p.Arg481Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 64974022: 64974022
10 CAPN1 NM_005186.3(CAPN1): c.1442G> A (p.Arg481Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 65206551: 65206551

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 endoplasmic reticulum membrane GO:0005789 9.43 CPT1C CYP7B1 FA2H GBA2 PLD3 PNPLA6
2 endoplasmic reticulum GO:0005783 9.17 CPT1C CYP7B1 FA2H GBA2 KIF1C PLD3
3 nuclear transcription factor complex GO:0044798 9.16 KLF4 SOX2

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

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.1 CPT1C CYP7B1 FA2H GBA2 PLD3 PNPLA6

Sources for Spastic Paraplegia 76, Autosomal Recessive

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10 dbSNP
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