SPG52
MCID: SPS122
MIFTS: 39

Spastic Paraplegia 52, Autosomal Recessive (SPG52)

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 52, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 52, Autosomal Recessive:

Name: Spastic Paraplegia 52, Autosomal Recessive 57 72 29 13 6 70
Spg52 57 12 72
Hereditary Spastic Paraplegia 52 12 15
Cpsq6 12 72
Cerebral Palsy, Spastic Quadriplegic, 6, Formerly; Cpsq6, Formerly 57
Cerebral Palsy, Spastic Quadriplegic, 6, Formerly 57
Palsy, Cerebral, Spastic Quadriplegic, Type 6 39
Autosomal Recessive Spastic Paraplegia 52 12
Cerebral Palsy, Spastic Quadriplegic 6 72
Spastic Quadriplegic Cerebral Palsy 6 12
Cpsq6, Formerly 57

Characteristics:

OMIM®:

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

Miscellaneous:
onset at birth
two unrelated families have been reported (last curated may 2016)


HPO:

31
spastic paraplegia 52, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Spastic Paraplegia 52, Autosomal Recessive

UniProtKB/Swiss-Prot : 72 Spastic paraplegia 52, autosomal recessive: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG52 is characterized by neonatal hypotonia that progresses to hypertonia and spasticity, and severe mental retardation with poor or absent speech development. Some patients may have seizures.

MalaCards based summary : Spastic Paraplegia 52, Autosomal Recessive, also known as spg52, is related to cerebral palsy and paraplegia, and has symptoms including muscle spasticity An important gene associated with Spastic Paraplegia 52, Autosomal Recessive is AP4S1 (Adaptor Related Protein Complex 4 Subunit Sigma 1), and among its related pathways/superpathways are Clathrin derived vesicle budding and Lysosome. Affiliated tissues include brain, and related phenotypes are focal-onset seizure and febrile seizure (within the age range of 3 months to 6 years)

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the AP4S1 gene on chromosome 14q12.

OMIM® : 57 Spastic quadriplegia-52 is an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development (summary by Abou Jamra et al., 2011). Some patients may have seizures (Hardies et al., 2015). (614067) (Updated 05-Apr-2021)

Related Diseases for Spastic Paraplegia 52, 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 52, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 72)
# Related Disease Score Top Affiliating Genes
1 cerebral palsy 29.7 AP4S1 AP4M1 AP4E1 AP4B1
2 paraplegia 27.6 ZFYVE26 SPG21 SPG11 RTN2 AP5Z1 AP4S1
3 hereditary spastic paraplegia 27.2 ZFYVE26 SPG21 SPG11 RTN2 PGAP1 AP5Z1
4 horner's syndrome 10.2 AP4S1 AP4B1
5 hermansky-pudlak syndrome 2 10.1 AP4M1 AP4E1
6 spastic paraplegia, optic atrophy, and neuropathy 10.1 AP5Z1 AP4S1
7 spastic cerebral palsy 10.1 AP4S1 AP4B1
8 spastic paraplegia 28, autosomal recessive 10.1 SPG11 AP5Z1
9 spastic paraplegia 5a, autosomal recessive 10.1 ZFYVE26 SPG11
10 spastic paraplegia 16, x-linked 10.0 SPG21 SPG11
11 spinocerebellar ataxia, autosomal recessive 20 10.0 ZFYVE26 SPG11
12 spastic paraplegia 14, autosomal recessive 10.0 SPG21 SPG11
13 spastic paraplegia 29, autosomal dominant 10.0 ZFYVE26 SPG21
14 spastic paraplegia 25, autosomal recessive 10.0 ZFYVE26 SPG21
15 spastic paraplegia 19, autosomal dominant 10.0 ZFYVE26 SPG21
16 spastic paraplegia 37, autosomal dominant 10.0 ZFYVE26 SPG21
17 spastic paraplegia 34, x-linked 9.9 ZFYVE26 SPG21
18 charcot-marie-tooth disease, axonal, type 2r 9.9 ZFYVE26 SPG21
19 mast syndrome 9.9 SPG21 SPG11
20 ap-4-associated hereditary spastic paraplegia 9.9 AP4S1 AP4M1 AP4E1 AP4B1
21 spastic diplegia 9.9 AP4S1 AP4M1 AP4E1 AP4B1
22 alacrima, achalasia, and mental retardation syndrome 9.9
23 spastic paraparesis 9.9
24 cerebral atrophy 9.9
25 febrile seizures 9.9
26 spasticity 9.9
27 quadriplegia 9.9 AP4S1 AP4M1 AP4E1 AP4B1
28 charcot-marie-tooth disease, axonal, type 2t 9.9 ZFYVE26 SPG21
29 amyotrophic lateral sclerosis type 5 9.9 ZFYVE26 SPG11 AP5Z1
30 motor peripheral neuropathy 9.9 ZFYVE26 SPG11
31 spastic paraplegia 20, autosomal recessive 9.8 ZFYVE26 SPG21
32 hereditary spastic paraplegia 30 9.8 SPG21 SPG11 AP5Z1
33 spastic paraplegia 54, autosomal recessive 9.8 SPG21 SPG11 AP5Z1
34 hereditary spastic paraplegia 23 9.8 ZFYVE26 SPG21 SPG11
35 spastic paraplegia 49, autosomal recessive 9.8 ZFYVE26 SPG21 SPG11
36 spastic paraplegia 55, autosomal recessive 9.8 ZFYVE26 SPG21 SPG11
37 spastic paraplegia 26, autosomal recessive 9.7 SPG21 SPG11 PGAP1
38 spastic paraplegia 3, autosomal dominant 9.7 SPG11 RTN2
39 spastic paraplegia 63, autosomal recessive 9.6 SPG21 SPG11 PGAP1 AP4E1
40 spastic paraplegia 45, autosomal recessive 9.6 SPG21 SPG11 PGAP1 AP4E1
41 spastic paraplegia 18, autosomal recessive 9.6 ZFYVE26 SPG21 SPG11 AP5Z1
42 spastic paraplegia 11, autosomal recessive 9.6 ZFYVE26 SPG21 SPG11 AP5Z1
43 spastic paraplegia 32, autosomal recessive 9.6 SPG21 SPG11 AP4S1 AP4E1 AP4B1
44 spastic paraplegia 46, autosomal recessive 9.6 ZFYVE26 SPG21 SPG11 AP5Z1
45 spastic paraplegia 39, autosomal recessive 9.6 ZFYVE26 SPG21 SPG11 AP5Z1
46 spastic paraplegia 6, autosomal dominant 9.6 ZFYVE26 SPG21 SPG11 AP5Z1
47 spastic paraplegia 15, autosomal recessive 9.6 ZFYVE26 SPG21 SPG11 AP5Z1
48 spastic paraplegia 35, autosomal recessive 9.6 ZFYVE26 SPG21 SPG11 AP5Z1
49 spastic paraplegia 8, autosomal dominant 9.6 ZFYVE26 SPG21 SPG11 AP5Z1
50 spastic paraplegia 44, autosomal recessive 9.6 SPG21 SPG11 PGAP1 AP5Z1

Graphical network of the top 20 diseases related to Spastic Paraplegia 52, Autosomal Recessive:



Diseases related to Spastic Paraplegia 52, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 52, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 52, Autosomal Recessive:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 focal-onset seizure 31 occasional (7.5%) HP:0007359
2 febrile seizure (within the age range of 3 months to 6 years) 31 occasional (7.5%) HP:0002373
3 spasticity 31 HP:0001257
4 hyperreflexia 31 HP:0001347
5 high palate 31 HP:0000218
6 coarse facial features 31 HP:0000280
7 global developmental delay 31 HP:0001263
8 hypertelorism 31 HP:0000316
9 wide nasal bridge 31 HP:0000431
10 thick vermilion border 31 HP:0012471
11 microcephaly 31 HP:0000252
12 short stature 31 HP:0004322
13 flexion contracture 31 HP:0001371
14 intellectual disability, severe 31 HP:0010864
15 talipes equinovarus 31 HP:0001762
16 wide mouth 31 HP:0000154
17 short philtrum 31 HP:0000322
18 bulbous nose 31 HP:0000414
19 cerebral palsy 31 HP:0100021
20 spastic paraplegia 31 HP:0001258
21 babinski sign 31 HP:0003487
22 prominent nose 31 HP:0000448
23 loss of ability to walk 31 HP:0006957
24 muscular hypotonia of the trunk 31 HP:0008936
25 facial hypotonia 31 HP:0000297

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
loss of ability to walk
extensor plantar responses
mental retardation, severe
more
Head And Neck Eyes:
hypertelorism

Growth Height:
short stature

Skeletal Feet:
talipes equinovarus

Head And Neck Nose:
bulbous nose
prominent nose
broad nasal bridge

Neurologic Behavioral Psychiatric Manifestations:
stereotypic laughter
shy character
amicable character

Head And Neck Face:
coarse facial features
short philtrum
facial hypotonia

Head And Neck Head:
microcephaly

Muscle Soft Tissue:
hypertonia
axial hypotonia
decreased shank muscle mass

Head And Neck Mouth:
wide mouth
high-arched palate
full lips

Skeletal:
joint contractures

Clinical features from OMIM®:

614067 (Updated 05-Apr-2021)

UMLS symptoms related to Spastic Paraplegia 52, Autosomal Recessive:


muscle spasticity

Drugs & Therapeutics for Spastic Paraplegia 52, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 52, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 52, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 52, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 52, Autosomal Recessive 29 AP4S1

Anatomical Context for Spastic Paraplegia 52, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 52, Autosomal Recessive:

40
Brain

Publications for Spastic Paraplegia 52, Autosomal Recessive

Articles related to Spastic Paraplegia 52, Autosomal Recessive:

# Title Authors PMID Year
1
Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly. 57 6
25552650 2015
2
Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. 57 6
21620353 2011
3
Utilizing RNA and outlier analysis to identify an intronic splice-altering variant in AP4S1 in a sibling pair with progressive spastic paraplegia. 6
31660686 2020
4
A homozygous splice variant in AP4S1 mimicking neurodegeneration with brain iron accumulation. 6
28150420 2017
5
Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia. 61
32979048 2020
6
Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52. 61
32216065 2020
7
Adaptor protein complex 4 deficiency: a paradigm of childhood-onset hereditary spastic paraplegia caused by defective protein trafficking. 61
31915823 2020
8
Generation and characterization of six human induced pluripotent stem cell lines (iPSC) from three families with AP4B1-associated hereditary spastic paraplegia (SPG47). 61
31525725 2019
9
Identification of mutations in AP4S1/SPG52 through next generation sequencing in three families. 61
27444738 2016
10
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms. 61
23897027 2013

Variations for Spastic Paraplegia 52, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 52, Autosomal Recessive:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AP4S1 NM_001128126.3(AP4S1):c.138+3_138+6del Microsatellite Pathogenic 234925 rs876661295 GRCh37: 14:31535539-31535542
GRCh38: 14:31066333-31066336
2 AP4S1 NM_001128126.3(AP4S1):c.124C>T (p.Arg42Ter) SNV Pathogenic 30658 rs387906970 GRCh37: 14:31535526-31535526
GRCh38: 14:31066320-31066320
3 AP4S1 NM_001128126.3(AP4S1):c.289C>T (p.Arg97Ter) SNV Pathogenic/Likely pathogenic 234924 rs200440467 GRCh37: 14:31542174-31542174
GRCh38: 14:31072968-31072968
4 AP4S1 NM_001128126.3(AP4S1):c.138+2T>G SNV Likely pathogenic 417874 rs377679827 GRCh37: 14:31535542-31535542
GRCh38: 14:31066336-31066336
5 AP4S1 NM_001128126.3(AP4S1):c.295-3C>A SNV Likely pathogenic 210218 rs185246578 GRCh37: 14:31549776-31549776
GRCh38: 14:31080570-31080570
6 AP4S1 NM_001128126.3(AP4S1):c.306+4191A>G SNV Uncertain significance 128407 rs200969079 GRCh37: 14:31553981-31553981
GRCh38: 14:31084775-31084775
7 AP4S1 NM_001128126.3(AP4S1):c.29A>G (p.Lys10Arg) SNV Uncertain significance 434248 rs147135554 GRCh37: 14:31535431-31535431
GRCh38: 14:31066225-31066225
8 AP4S1 NM_001128126.3(AP4S1):c.83G>A (p.Arg28His) SNV Uncertain significance 527988 rs201972703 GRCh37: 14:31535485-31535485
GRCh38: 14:31066279-31066279

Expression for Spastic Paraplegia 52, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 52, Autosomal Recessive.

Pathways for Spastic Paraplegia 52, Autosomal Recessive

Pathways related to Spastic Paraplegia 52, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.64 AP4S1 AP4M1 AP4E1 AP4B1
2 11.03 AP4S1 AP4M1 AP4E1 AP4B1

GO Terms for Spastic Paraplegia 52, Autosomal Recessive

Cellular components related to Spastic Paraplegia 52, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.73 SPG21 ATG9A AP4S1 AP4M1 AP4E1 AP4B1
2 trans-Golgi network GO:0005802 9.54 ATG9A AP4M1 AP4B1
3 trans-Golgi network membrane GO:0032588 9.46 AP4S1 AP4M1 AP4E1 AP4B1
4 membrane coat GO:0030117 9.4 AP4E1 AP4B1
5 clathrin adaptor complex GO:0030131 9.32 AP4M1 AP4B1
6 endosome lumen GO:0031904 9.26 AP4S1 AP4M1 AP4E1 AP4B1
7 AP-4 adaptor complex GO:0030124 8.92 AP4S1 AP4M1 AP4E1 AP4B1

Biological processes related to Spastic Paraplegia 52, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intracellular protein transport GO:0006886 9.62 AP4S1 AP4M1 AP4E1 AP4B1
2 vesicle-mediated transport GO:0016192 9.56 AP4S1 AP4M1 AP4E1 AP4B1
3 protein localization GO:0008104 9.46 AP4S1 AP4M1 AP4E1 AP4B1
4 protein targeting GO:0006605 9.26 AP4S1 AP4M1 AP4E1 AP4B1
5 protein transport GO:0015031 9.17 PGAP1 ATG9A AP5Z1 AP4S1 AP4M1 AP4E1

Sources for Spastic Paraplegia 52, 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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