MCID: AP4001
MIFTS: 29

Ap-4-Associated Hereditary Spastic Paraplegia

Categories: Neuronal diseases, Rare diseases

Aliases & Classifications for Ap-4-Associated Hereditary Spastic Paraplegia

MalaCards integrated aliases for Ap-4-Associated Hereditary Spastic Paraplegia:

Name: Ap-4-Associated Hereditary Spastic Paraplegia 24 53
Severe Intellectual Disability and Progressive Spastic Paraplegia 53 59
Adaptor Protein Complex 4 Deficiency 24 53
Ap-4 Deficiency Syndrome 24 53
Ap4 Deficiency Syndrome 53 59
Ap-4-Associated Hsp 24 53
Ap-4 Deficiency 24 53

Characteristics:

Orphanet epidemiological data:

59
severe intellectual disability and progressive spastic paraplegia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Orphanet 59 ORPHA280763

Summaries for Ap-4-Associated Hereditary Spastic Paraplegia

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 280763DefinitionSevere intellectual disability and progressive spastic paraplegia is a rare complex spastic paraplegia characterized by an early onset hypotonia that progresses to spasticity, global developmental delay, severe intellectual disability and speech impairment, microcephaly, short stature and dysmorphic features. Patients often become non-ambulatory, and some develop seizures and stereotypic laughter.Visit the Orphanet disease page for more resources.

MalaCards based summary : Ap-4-Associated Hereditary Spastic Paraplegia, also known as severe intellectual disability and progressive spastic paraplegia, is related to spastic paraplegia 52, autosomal recessive and hereditary spastic paraplegia. An important gene associated with Ap-4-Associated Hereditary Spastic Paraplegia is AP4B1 (Adaptor Related Protein Complex 4 Subunit Beta 1), and among its related pathways/superpathways are Vesicle-mediated transport and Clathrin derived vesicle budding. Affiliated tissues include brain, and related phenotypes are microcephaly and intellectual disability, severe

GeneReviews: NBK535153

Related Diseases for Ap-4-Associated Hereditary Spastic Paraplegia

Graphical network of the top 20 diseases related to Ap-4-Associated Hereditary Spastic Paraplegia:



Diseases related to Ap-4-Associated Hereditary Spastic Paraplegia

Symptoms & Phenotypes for Ap-4-Associated Hereditary Spastic Paraplegia

Human phenotypes related to Ap-4-Associated Hereditary Spastic Paraplegia:

59 32 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
2 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
3 progressive spastic paraplegia 59 32 hallmark (90%) Very frequent (99-80%) HP:0007020
4 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
5 coarse facial features 59 32 frequent (33%) Frequent (79-30%) HP:0000280
6 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
7 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
8 babinski sign 59 32 frequent (33%) Frequent (79-30%) HP:0003487
9 dystonia 59 32 frequent (33%) Frequent (79-30%) HP:0001332
10 waddling gait 59 32 frequent (33%) Frequent (79-30%) HP:0002515
11 cerebral cortical atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0002120
12 bulbous nose 59 32 frequent (33%) Frequent (79-30%) HP:0000414
13 difficulty walking 59 32 frequent (33%) Frequent (79-30%) HP:0002355
14 cerebellar atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0001272
15 drooling 59 32 frequent (33%) Frequent (79-30%) HP:0002307
16 poor speech 59 32 frequent (33%) Frequent (79-30%) HP:0002465
17 spastic dysarthria 59 32 frequent (33%) Frequent (79-30%) HP:0002464
18 facial hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0000297
19 high palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000218
20 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
21 pes planus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001763
22 stereotypy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000733
23 short philtrum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000322
24 narrow forehead 59 32 occasional (7.5%) Occasional (29-5%) HP:0000341
25 wide mouth 59 32 occasional (7.5%) Occasional (29-5%) HP:0000154
26 shyness 59 32 occasional (7.5%) Occasional (29-5%) HP:0100962
27 everted upper lip vermilion 59 32 occasional (7.5%) Occasional (29-5%) HP:0010803
28 hypoplasia of the corpus callosum 59 32 occasional (7.5%) Occasional (29-5%) HP:0002079
29 abnormality of the periventricular white matter 59 32 occasional (7.5%) Occasional (29-5%) HP:0002518
30 overweight 59 32 occasional (7.5%) Occasional (29-5%) HP:0025502
31 strabismus 59 32 very rare (1%) Very rare (<4-1%) HP:0000486
32 genu recurvatum 59 32 very rare (1%) Very rare (<4-1%) HP:0002816
33 amblyopia 59 32 very rare (1%) Very rare (<4-1%) HP:0000646
34 generalized joint laxity 59 32 very rare (1%) Very rare (<4-1%) HP:0002761
35 acetabular dysplasia 59 32 very rare (1%) Very rare (<4-1%) HP:0008807
36 muscular hypotonia 59 Very frequent (99-80%)
37 spasticity 59 Frequent (79-30%)

Drugs & Therapeutics for Ap-4-Associated Hereditary Spastic Paraplegia

Search Clinical Trials , NIH Clinical Center for Ap-4-Associated Hereditary Spastic Paraplegia

Genetic Tests for Ap-4-Associated Hereditary Spastic Paraplegia

Anatomical Context for Ap-4-Associated Hereditary Spastic Paraplegia

MalaCards organs/tissues related to Ap-4-Associated Hereditary Spastic Paraplegia:

41
Brain

Publications for Ap-4-Associated Hereditary Spastic Paraplegia

Articles related to Ap-4-Associated Hereditary Spastic Paraplegia:

(show all 24)
# 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. 4 71
25552650 2015
2
Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. 4 71
21620353 2011
3
Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. 4 71
20972249 2011
4
Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy. 4 71
19559397 2009
5
AP-4-Associated Hereditary Spastic Paraplegia 38 71
30543385 2018
6
An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome. 71
24781758 2015
7
Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: expansion of the facial and neuroimaging features. 71
24700674 2014
8
Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) . 71
22290197 2012
9
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 71
21937992 2011
10
Practice parameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. 71
15037681 2004
11
AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A. 4
30262884 2018
12
Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome. 4
29698489 2018
13
Clinical and genetic characterization of AP4B1-associated SPG47. 4
29193663 2018
14
AP4 deficiency: A novel form of neurodegeneration with brain iron accumulation? 4
29473051 2018
15
AP-4 mediates export of ATG9A from the trans-Golgi network to promote autophagosome formation. 4
29180427 2017
16
A homozygous splice variant in AP4S1 mimicking neurodegeneration with brain iron accumulation. 4
28150420 2017
17
Nomenclature of genetic movement disorders: Recommendations of the international Parkinson and movement disorder society task force. 4
27079681 2016
18
Molecular Basis for the Interaction Between AP4 β4 and its Accessory Protein, Tepsin. 4
26756312 2016
19
Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex. 4
26542808 2015
20
Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering. 4
26544806 2015
21
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms. 4
23897027 2013
22
Adaptor protein complexes AP-4 and AP-5: new players in endosomal trafficking and progressive spastic paraplegia. 4
23167973 2013
23
Characterization of a fourth adaptor-related protein complex. 4
10436028 1999
24
AP-4, a novel protein complex related to clathrin adaptors. 4
10066790 1999

Variations for Ap-4-Associated Hereditary Spastic Paraplegia

Expression for Ap-4-Associated Hereditary Spastic Paraplegia

Search GEO for disease gene expression data for Ap-4-Associated Hereditary Spastic Paraplegia.

Pathways for Ap-4-Associated Hereditary Spastic Paraplegia

Pathways related to Ap-4-Associated Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.56 AP4S1 AP4M1 AP4E1 AP4B1
2
Show member pathways
11.64 AP4S1 AP4M1 AP4E1 AP4B1
3 11.01 AP4S1 AP4M1 AP4E1 AP4B1

GO Terms for Ap-4-Associated Hereditary Spastic Paraplegia

Cellular components related to Ap-4-Associated Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.62 AP4S1 AP4M1 AP4E1 AP4B1
2 trans-Golgi network membrane GO:0032588 9.46 AP4S1 AP4M1 AP4E1 AP4B1
3 trans-Golgi network GO:0005802 9.4 AP4M1 AP4B1
4 membrane coat GO:0030117 9.37 AP4E1 AP4B1
5 clathrin adaptor complex GO:0030131 9.26 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 Ap-4-Associated Hereditary Spastic Paraplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.56 AP4S1 AP4M1 AP4E1 AP4B1
2 vesicle-mediated transport GO:0016192 9.5 AP4M1 AP4E1 AP4B1
3 intracellular protein transport GO:0006886 9.46 AP4S1 AP4M1 AP4E1 AP4B1
4 protein localization GO:0008104 9.26 AP4S1 AP4M1 AP4E1 AP4B1
5 protein targeting GO:0006605 8.92 AP4S1 AP4M1 AP4E1 AP4B1

Sources for Ap-4-Associated Hereditary Spastic Paraplegia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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