MCID: SPS117
MIFTS: 37

Spastic Paraplegia 10, Autosomal Dominant

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Eye diseases, Gastrointestinal diseases, Bone diseases, Mental diseases, Metabolic diseases

Aliases & Classifications for Spastic Paraplegia 10, Autosomal Dominant

MalaCards integrated aliases for Spastic Paraplegia 10, Autosomal Dominant:

Name: Spastic Paraplegia 10, Autosomal Dominant 57 75 13 73
Spg10 57 12 59 75 55
Autosomal Dominant Spastic Paraplegia Type 10 12 59
Hereditary Spastic Paraplegia 10 12 15
Spastic Paraplegia 10 with or Without Peripheral Neuropathy 57
Paraplegia, Spastic, Autosomal Dominant, Type 10 40
Autosomal Dominant Spastic Paraplegia 10 12

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant spastic paraplegia type 10
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
progressive disorder
variable age at onset, early childhood to adult


HPO:

32
spastic paraplegia 10, autosomal dominant:
Onset and clinical course phenotypic variability progressive
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 604187
Disease Ontology 12 DOID:0110763
ICD10 33 G11.4
MESH via Orphanet 45 C537482
UMLS via Orphanet 74 C1858712
ICD10 via Orphanet 34 G11.4
MedGen 42 C1858712
MeSH 44 D015419
UMLS 73 C1858712

Summaries for Spastic Paraplegia 10, Autosomal Dominant

OMIM : 57 Spastic paraplegia-10 is an autosomal dominant neurologic disorder with variable manifestations. Some patients have onset of a 'pure' spastic paraplegia, with lower limb spasticity, hyperreflexia, extensor plantar responses, and variable involvement of the upper limbs beginning in childhood or young adulthood. Some patients show distal sensory impairment, which can be part of the 'pure' phenotype. However, some patients also show an axonal sensorimotor peripheral neuropathy with distal sensory impairment and distal muscle atrophy reminiscent of Charcot-Marie-Tooth disease type 2 (see, e.g., CMT2A, 118210). Rarely, patients with KIF5A mutations may have additional neurologic features, including parkinsonism or cognitive decline, consistent with a 'complicated' phenotype. Spastic paraplegia and peripheral neuropathy in isolation may represent extreme ends of the phenotypic spectrum of KIF5A mutations (summary by Goizet et al., 2009 and Crimella et al., 2012). (604187)

MalaCards based summary : Spastic Paraplegia 10, Autosomal Dominant, also known as spg10, is related to spastic paraplegia 10 and hereditary spastic paraplegia 51, and has symptoms including urgency of micturition An important gene associated with Spastic Paraplegia 10, Autosomal Dominant is KIF5A (Kinesin Family Member 5A), and among its related pathways/superpathways are Endocytosis and Cytoskeleton remodeling Neurofilaments. Related phenotypes are urinary urgency and urinary incontinence

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the KIF5A gene on chromosome 12q13.

UniProtKB/Swiss-Prot : 75 Spastic paraplegia 10, autosomal dominant: 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.

Related Diseases for Spastic Paraplegia 10, Autosomal Dominant

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 51
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Autosomal Recessive Spastic Paraplegia Type 60 Autosomal Recessive Spastic Paraplegia Type 59
Autosomal Recessive Spastic Paraplegia Type 68 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

Diseases related to Spastic Paraplegia 10, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 10 11.4
2 hereditary spastic paraplegia 51 10.1 AP5Z1 RTN2
3 spastic paraplegia 52, autosomal recessive 10.1 AP5Z1 RTN2
4 spastic paraplegia 50, autosomal recessive 10.1 AP5Z1 RTN2
5 spastic paraplegia 28, autosomal recessive 10.0 AP5Z1 RTN2
6 spastic paraplegia 44, autosomal recessive 10.0 AP5Z1 ZFYVE27
7 spastic paraplegia 54, autosomal recessive 10.0 AP5Z1 RTN2
8 spastic paraplegia 18, autosomal recessive 10.0 AP5Z1 REEP1
9 spastic paraplegia 47, autosomal recessive 9.9 AP5Z1 REEP1
10 spastic paraplegia 39, autosomal recessive 9.9 AP5Z1 REEP1
11 spastic paraplegia 13, autosomal dominant 9.8 AP5Z1 ATL1
12 spastic paraplegia 61, autosomal recessive 9.8 ATL1 REEP1 RTN2
13 spastic paraplegia 30, autosomal recessive 9.8 AP5Z1 REEP1
14 spastic paraplegia 32, autosomal recessive 9.7 ATL1 SPG11
15 spastic paraplegia 42, autosomal dominant 9.7 AP5Z1 REEP1
16 spastic paraplegia 48, autosomal recessive 9.5 AP5Z1 SPG11
17 spastic paraplegia 15, autosomal recessive 9.2 AP5Z1 SPG11
18 axonal neuropathy 9.2 KIF5A SPG11
19 spastic paraplegia 35, autosomal recessive 9.1 AP5Z1 SPG11
20 spastic paraplegia 6, autosomal dominant 9.1 AP5Z1 ATL1 KIF5A REEP1
21 spastic paraplegia 33, autosomal dominant 9.0 AP5Z1 REEP1 RTN2 ZFYVE27
22 spastic paraplegia 31, autosomal dominant 8.6 AP5Z1 ATL1 REEP1 RTN2 ZFYVE27
23 spastic paraplegia 2, x-linked 8.5 AP5Z1 ATL1 REEP1 RTN2 ZFYVE27
24 spastic paraplegia 8, autosomal dominant 8.5 AP5Z1 ATL1 REEP1 SPG11
25 masa syndrome 8.5 AP5Z1 ATL1 REEP1 SPG11
26 spastic paraplegia 4, autosomal dominant 8.3 ATL1 REEP1 RTN2 SPG11 ZFYVE27
27 spastic paraplegia 3, autosomal dominant 8.3 ATL1 REEP1 RTN2 SPG11 ZFYVE27
28 spastic paraplegia 12, autosomal dominant 8.2 AP5Z1 ATL1 KIF5A REEP1 RTN2 ZFYVE27
29 paraplegia 7.2 AP5Z1 ATL1 KIF5A REEP1 RTN2 SPG11
30 hereditary spastic paraplegia 7.2 AP5Z1 ATL1 KIF5A REEP1 RTN2 SPG11

Graphical network of the top 20 diseases related to Spastic Paraplegia 10, Autosomal Dominant:



Diseases related to Spastic Paraplegia 10, Autosomal Dominant

Symptoms & Phenotypes for Spastic Paraplegia 10, Autosomal Dominant

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
hyperreflexia
lower limb spasticity
spastic gait
extensor plantar responses
lower limb weakness
more
Skeletal Feet:
pes cavus

Neurologic Peripheral Nervous System:
distal sensory impairment
decreased vibratory sense in the lower limbs
axonal sensorimotor peripheral neuropathy
upper limb sensory loss may occur later

Skeletal Spine:
scoliosis

Genitourinary Bladder:
urinary incontinence
urinary urgency
sphincter disturbances

Muscle Soft Tissue:
amyotrophy of the lower limbs (in some patients)
amyotrophy of the upper limbs (in some patients)


Clinical features from OMIM:

604187

Human phenotypes related to Spastic Paraplegia 10, Autosomal Dominant:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 urinary urgency 32 HP:0000012
2 urinary incontinence 32 HP:0000020
3 ataxia 32 occasional (7.5%) HP:0001251
4 spastic paraplegia 32 HP:0001258
5 parkinsonism 32 occasional (7.5%) HP:0001300
6 hyperreflexia 32 HP:0001347
7 pes cavus 32 HP:0001761
8 spastic gait 32 HP:0002064
9 impaired vibration sensation in the lower limbs 32 HP:0002166
10 scoliosis 32 HP:0002650
11 urinary bladder sphincter dysfunction 32 HP:0002839
12 distal sensory impairment 32 HP:0002936
13 babinski sign 32 HP:0003487
14 lower limb muscle weakness 32 HP:0007340
15 ankle clonus 32 HP:0011448
16 knee clonus 32 HP:0011449

UMLS symptoms related to Spastic Paraplegia 10, Autosomal Dominant:


urgency of micturition

Drugs & Therapeutics for Spastic Paraplegia 10, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 10, Autosomal Dominant

Genetic Tests for Spastic Paraplegia 10, Autosomal Dominant

Anatomical Context for Spastic Paraplegia 10, Autosomal Dominant

Publications for Spastic Paraplegia 10, Autosomal Dominant

Variations for Spastic Paraplegia 10, Autosomal Dominant

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 10, Autosomal Dominant:

75 (show all 13)
# Symbol AA change Variation ID SNP ID
1 KIF5A p.Asn256Ser VAR_032842 rs121434441
2 KIF5A p.Arg280Cys VAR_032843 rs121434442
3 KIF5A p.Ala361Val VAR_032844 rs121434444
4 KIF5A p.Tyr276Cys VAR_033108 rs121434443
5 KIF5A p.Lys253Asn VAR_046744
6 KIF5A p.Tyr63Cys VAR_058741
7 KIF5A p.Met198Thr VAR_058742
8 KIF5A p.Arg204Gln VAR_058743 rs387907287
9 KIF5A p.Glu251Lys VAR_058744 rs387907285
10 KIF5A p.Lys257Asn VAR_058746
11 KIF5A p.Arg280His VAR_058747 rs387907288
12 KIF5A p.Arg280Leu VAR_058748
13 KIF5A p.Ser203Cys VAR_066616

ClinVar genetic disease variations for Spastic Paraplegia 10, Autosomal Dominant:

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 KIF5A NM_004984.3(KIF5A): c.767A> G (p.Asn256Ser) single nucleotide variant Pathogenic rs121434441 GRCh37 Chromosome 12, 57962798: 57962798
2 KIF5A NM_004984.3(KIF5A): c.767A> G (p.Asn256Ser) single nucleotide variant Pathogenic rs121434441 GRCh38 Chromosome 12, 57569015: 57569015
3 KIF5A NM_004984.3(KIF5A): c.838C> T (p.Arg280Cys) single nucleotide variant Pathogenic rs121434442 GRCh37 Chromosome 12, 57963057: 57963057
4 KIF5A NM_004984.3(KIF5A): c.838C> T (p.Arg280Cys) single nucleotide variant Pathogenic rs121434442 GRCh38 Chromosome 12, 57569274: 57569274
5 KIF5A NM_004984.3(KIF5A): c.827A> G (p.Tyr276Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121434443 GRCh37 Chromosome 12, 57963046: 57963046
6 KIF5A NM_004984.3(KIF5A): c.827A> G (p.Tyr276Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121434443 GRCh38 Chromosome 12, 57569263: 57569263
7 KIF5A NM_004984.3(KIF5A): c.1082C> T (p.Ala361Val) single nucleotide variant Pathogenic rs121434444 GRCh37 Chromosome 12, 57963431: 57963431
8 KIF5A NM_004984.3(KIF5A): c.1082C> T (p.Ala361Val) single nucleotide variant Pathogenic rs121434444 GRCh38 Chromosome 12, 57569648: 57569648
9 KIF5A NM_004984.3(KIF5A): c.751G> A (p.Glu251Lys) single nucleotide variant Pathogenic rs387907285 GRCh37 Chromosome 12, 57962782: 57962782
10 KIF5A NM_004984.3(KIF5A): c.751G> A (p.Glu251Lys) single nucleotide variant Pathogenic rs387907285 GRCh38 Chromosome 12, 57568999: 57568999
11 KIF5A NM_004984.3(KIF5A): c.611G> A (p.Arg204Gln) single nucleotide variant Pathogenic rs387907287 GRCh37 Chromosome 12, 57961298: 57961298
12 KIF5A NM_004984.3(KIF5A): c.611G> A (p.Arg204Gln) single nucleotide variant Pathogenic rs387907287 GRCh38 Chromosome 12, 57567515: 57567515
13 KIF5A NM_004984.3(KIF5A): c.704G> A (p.Gly235Glu) single nucleotide variant Pathogenic rs387907289 GRCh37 Chromosome 12, 57961391: 57961391
14 KIF5A NM_004984.3(KIF5A): c.704G> A (p.Gly235Glu) single nucleotide variant Pathogenic rs387907289 GRCh38 Chromosome 12, 57567608: 57567608
15 KIF5A NM_004984.3(KIF5A): c.694G> A (p.Asp232Asn) single nucleotide variant Pathogenic rs690016545 GRCh37 Chromosome 12, 57961381: 57961381
16 KIF5A NM_004984.3(KIF5A): c.694G> A (p.Asp232Asn) single nucleotide variant Pathogenic rs690016545 GRCh38 Chromosome 12, 57567598: 57567598
17 KIF5A NM_004984.3(KIF5A): c.2769G> A (p.Arg923=) single nucleotide variant Benign/Likely benign rs35225609 GRCh37 Chromosome 12, 57975211: 57975211
18 KIF5A NM_004984.3(KIF5A): c.2769G> A (p.Arg923=) single nucleotide variant Benign/Likely benign rs35225609 GRCh38 Chromosome 12, 57581428: 57581428
19 KIF5A NM_004984.3(KIF5A): c.2957C> T (p.Pro986Leu) single nucleotide variant Benign/Likely benign rs113247976 GRCh38 Chromosome 12, 57581917: 57581917
20 KIF5A NM_004984.3(KIF5A): c.2957C> T (p.Pro986Leu) single nucleotide variant Benign/Likely benign rs113247976 GRCh37 Chromosome 12, 57975700: 57975700
21 KIF5A NM_004984.3(KIF5A): c.2839A> G (p.Thr947Ala) single nucleotide variant Likely benign rs150672943 GRCh37 Chromosome 12, 57975281: 57975281
22 KIF5A NM_004984.3(KIF5A): c.2839A> G (p.Thr947Ala) single nucleotide variant Likely benign rs150672943 GRCh38 Chromosome 12, 57581498: 57581498
23 KIF5A NM_004984.3(KIF5A): c.799T> C (p.Ser267Pro) single nucleotide variant Likely pathogenic rs1131692233 GRCh38 Chromosome 12, 57569047: 57569047
24 KIF5A NM_004984.3(KIF5A): c.799T> C (p.Ser267Pro) single nucleotide variant Likely pathogenic rs1131692233 GRCh37 Chromosome 12, 57962830: 57962830

Expression for Spastic Paraplegia 10, Autosomal Dominant

Search GEO for disease gene expression data for Spastic Paraplegia 10, Autosomal Dominant.

Pathways for Spastic Paraplegia 10, Autosomal Dominant

Pathways related to Spastic Paraplegia 10, Autosomal Dominant according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.19 KIF5A KIF5C ZFYVE27
2
Show member pathways
10.99 KIF5A KIF5C

GO Terms for Spastic Paraplegia 10, Autosomal Dominant

Cellular components related to Spastic Paraplegia 10, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.95 AP5Z1 ATL1 KIF5A KIF5C REEP1 SPG11
2 endoplasmic reticulum membrane GO:0005789 9.62 ATL1 REEP1 RTN2 ZFYVE27
3 integral component of endoplasmic reticulum membrane GO:0030176 9.37 RTN2 ZFYVE27
4 axon GO:0030424 9.33 ATL1 SPG11 ZFYVE27
5 kinesin complex GO:0005871 9.26 KIF5A KIF5C
6 ciliary rootlet GO:0035253 8.96 KIF5A KIF5C
7 endoplasmic reticulum tubular network GO:0071782 8.8 ATL1 REEP1 ZFYVE27

Biological processes related to Spastic Paraplegia 10, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein localization GO:0008104 9.26 KIF5A KIF5C
2 cytoskeleton-dependent intracellular transport GO:0030705 9.16 KIF5A KIF5C
3 anterograde dendritic transport of neurotransmitter receptor complex GO:0098971 8.96 KIF5A KIF5C
4 synaptic vesicle transport GO:0048489 8.8 KIF5A KIF5C SPG11

Molecular functions related to Spastic Paraplegia 10, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule motor activity GO:0003777 9.16 KIF5A KIF5C
2 microtubule binding GO:0008017 9.13 KIF5A KIF5C REEP1
3 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 8.62 KIF5A KIF5C

Sources for Spastic Paraplegia 10, Autosomal Dominant

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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