Spastic Paraplegia 12, Autosomal Dominant disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: SPS131 MIFTS: 35	Spastic Paraplegia 12, Autosomal Dominant Categories: Genetic diseases, Neuronal diseases, Rare diseases, Eye diseases, Gastrointestinal diseases, Bone diseases, Mental diseases, Metabolic diseases
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Aliases & Classifications for Spastic Paraplegia 12, Autosomal Dominant

MalaCards integrated aliases for Spastic Paraplegia 12, Autosomal Dominant:

Name: Spastic Paraplegia 12, Autosomal Dominant ⁵⁷ ⁷⁵ ¹³ ⁷³

Spg12 ⁵⁷ ¹² ⁵⁹ ⁷⁵

Autosomal Dominant Spastic Paraplegia Type 12 ¹² ⁵⁹

Hereditary Spastic Paraplegia 12 ¹² ¹⁵

Paraplegia, Spastic, Autosomal Dominant, Type 12 ⁴⁰

Autosomal Dominant Spastic Paraplegia 12 ¹²

Characteristics:

Orphanet epidemiological data:

⁵⁹

autosomal dominant spastic paraplegia type 12
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

OMIM:

⁵⁷

Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
later onset has been reported
age of onset 5 to 22 years (mean 6.9)

HPO:

³²

spastic paraplegia 12, autosomal dominant:
Onset and clinical course progressive
Inheritance autosomal dominant inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Neuronal diseases Eye diseases Gastrointestinal diseases Bone diseases Mental diseases

See all MalaCards categories (disease lists)

ICD10: ³³ ³⁴

Diseases of the nervous system

Systemic atrophies primarily affecting the central nervous system

Hereditary ataxia

Hereditary spastic paraplegia

Orphanet: ⁵⁹

Rare neurological diseases

External Ids:

OMIM ⁵⁷ 604805

Disease Ontology ¹² DOID:0110765

ICD10 ³³ G11.4

Orphanet ⁵⁹ ORPHA100993

MESH via Orphanet ⁴⁵ C537484

UMLS via Orphanet ⁷⁴ C1858106

ICD10 via Orphanet ³⁴ G11.4

MedGen ⁴² C1858106

MeSH ⁴⁴ D015419

UMLS ⁷³ C1858106

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Summaries for Spastic Paraplegia 12, Autosomal Dominant

UniProtKB/Swiss-Prot : ⁷⁵ Spastic paraplegia 12, 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.

MalaCards based summary : Spastic Paraplegia 12, Autosomal Dominant, also known as spg12, is related to spastic paraplegia 12 and hereditary spastic paraplegia 51, and has symptoms including urgency of micturition An important gene associated with Spastic Paraplegia 12, Autosomal Dominant is RTN2 (Reticulon 2). Affiliated tissues include spinal cord, and related phenotypes are hyperreflexia and degeneration of the lateral corticospinal tracts

OMIM : ⁵⁷ Spastic paraplegia-12 is an autosomal dominant neurodegenerative disorder characterized by lower limb spasticity and hyperreflexia, resulting in walking difficulties. Some patients may have urinary symptoms and distal sensory impairment. The age at onset is variable and can range from childhood to adulthood (summary by Montenegro et al., 2012). For a general description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600). (604805)

Disease Ontology : ¹² A hereditary spastic paraplegia that has material basis in mutation in the RTN2 gene on chromosome 19q13.

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Related Diseases for Spastic Paraplegia 12, 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 12, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 28)

#	Related Disease	Score	Top Affiliating Genes
1	spastic paraplegia 12	11.2
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 54, autosomal recessive	9.9	AP5Z1 RTN2
7	spastic paraplegia 48, autosomal recessive	9.7	AP5Z1 ERLIN2
8	spastic paraplegia 18, autosomal recessive	9.5	AP5Z1 ERLIN2 REEP1
9	spastic paraplegia 47, autosomal recessive	9.5	AP5Z1 ERLIN2 REEP1
10	spastic paraplegia 39, autosomal recessive	9.4	AP5Z1 ERLIN2 REEP1
11	spastic paraplegia 30, autosomal recessive	9.4	AP5Z1 ERLIN2 REEP1
12	spastic paraplegia 42, autosomal dominant	9.4	AP5Z1 ERLIN2 REEP1
13	spastic paraplegia 44, autosomal recessive	9.4	AP5Z1 ERLIN2 ZFYVE27
14	charcot-marie-tooth disease, axonal, type 2d	9.4	ATL1 SPAST
15	spastic paraplegia 35, autosomal recessive	9.2	AP5Z1 ERLIN2
16	spastic paraplegia 8, autosomal dominant	9.0	AP5Z1 ATL1 ERLIN2 REEP1
17	spastic paraplegia 61, autosomal recessive	9.0	ATL1 REEP1 RTN2 SPAST
18	masa syndrome	8.8	AP5Z1 ATL1 REEP1 SPAST
19	spastic paraplegia 13, autosomal dominant	8.5	AP5Z1 ATL1 ERLIN2 SPAST
20	spastic paraplegia 3, autosomal dominant	8.5	ATL1 REEP1 RTN2 SPAST ZFYVE27
21	spastic paraplegia 33, autosomal dominant	8.4	AP5Z1 REEP1 RTN2 SPAST ZFYVE27
22	spastic paraplegia 10, autosomal dominant	8.2	AP5Z1 ATL1 KIF5A REEP1 RTN2 ZFYVE27
23	spastic paraplegia 2, x-linked	8.1	AP5Z1 ATL1 ERLIN2 REEP1 RTN2 ZFYVE27
24	spastic paraplegia 31, autosomal dominant	7.9	AP5Z1 ATL1 REEP1 RTN2 SPAST ZFYVE27
25	spastic paraplegia 4, autosomal dominant	7.8	ATL1 ERLIN2 REEP1 RTN2 SPAST ZFYVE27
26	spastic paraplegia 6, autosomal dominant	7.5	AP5Z1 ATL1 ERLIN2 KIF5A REEP1 SPAST
27	hereditary spastic paraplegia	6.6	AP5Z1 ATL1 ERLIN2 KIF5A REEP1 RTN2
28	paraplegia	6.6	AP5Z1 ATL1 ERLIN2 KIF5A REEP1 RTN2

Graphical network of the top 20 diseases related to Spastic Paraplegia 12, Autosomal Dominant:

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Symptoms & Phenotypes for Spastic Paraplegia 12, 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

Genitourinary Bladder:
urinary incontinence
urinary urgency
sphincter disturbances

Skeletal Feet:
pes cavus

Neurologic Peripheral Nervous System:
decreased vibratory sense in the lower limbs

Clinical features from OMIM:

604805

Human phenotypes related to Spastic Paraplegia 12, Autosomal Dominant:

⁵⁹ ³² (show all 31)

#	Description	HPO Frequency	Orphanet Frequency	HPO Source Accession
1	hyperreflexia ⁵⁹ ³²		Very frequent (99-80%)	HP:0001347
2	degeneration of the lateral corticospinal tracts ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0002314
3	difficulty walking ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0002355
4	progressive spastic paraplegia ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0007020
5	lower limb muscle weakness ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0007340
6	urinary urgency ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0000012
7	urinary incontinence ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0000020
8	spastic gait ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0002064
9	limb ataxia ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0002070
10	impaired vibration sensation in the lower limbs ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0002166
11	clonus ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0002169
12	muscle cramps ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0003394
13	babinski sign ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0003487
14	lower limb amyotrophy ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0007210
15	progressive pes cavus ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0008075
16	impaired proprioception ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0010831
17	female sexual dysfunction ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0030014
18	male sexual dysfunction ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0040307
19	spinal cord lesion ⁵⁹ ³²	frequent (33%)	Frequent (79-30%)	HP:0100561
20	bowel incontinence ⁵⁹ ³²	occasional (7.5%)	Occasional (29-5%)	HP:0002607
21	hyperreflexia in upper limbs ⁵⁹ ³²	occasional (7.5%)	Occasional (29-5%)	HP:0007350
22	lower limb spasticity ⁵⁹		Very frequent (99-80%)
23	seizures ⁵⁹		Excluded (0%)
24	abnormality of the cerebrospinal fluid ⁵⁹		Excluded (0%)
25	emg abnormality ⁵⁹		Excluded (0%)
26	abnormal lower-limb motor evoked potentials ⁵⁹		Excluded (0%)
27	spastic paraplegia ³²			HP:0001258
28	pes cavus ³²			HP:0001761
29	urinary bladder sphincter dysfunction ³²			HP:0002839
30	ankle clonus ³²			HP:0011448
31	knee clonus ³²			HP:0011449

UMLS symptoms related to Spastic Paraplegia 12, Autosomal Dominant:

urgency of micturition

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Drugs & Therapeutics for Spastic Paraplegia 12, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 12, Autosomal Dominant

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Genetic Tests for Spastic Paraplegia 12, Autosomal Dominant

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Anatomical Context for Spastic Paraplegia 12, Autosomal Dominant

MalaCards organs/tissues related to Spastic Paraplegia 12, Autosomal Dominant:

⁴¹

Spinal Cord

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Publications for Spastic Paraplegia 12, Autosomal Dominant

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Genes for Spastic Paraplegia 12, Autosomal Dominant

Genes related to Spastic Paraplegia 12, Autosomal Dominant (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	RTN2	Reticulon 2	Protein Coding	1596.25	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative germline mutation ⁵⁹ Causative variation ⁷⁵ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Gene name Variants (show sections)	10677333 12427890 22232211 (more) 27165006
2	REEP1	Receptor Accessory Protein 1	Protein Coding	17.58	DISEASES inferred ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)
3	ATL1	Atlastin GTPase 1	Protein Coding	17.55	DISEASES inferred ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)
4	ZFYVE27	Zinc Finger FYVE-Type Containing 27	Protein Coding	17.42	DISEASES inferred ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)
5	AP5Z1	Adaptor Related Protein Complex 5 Subunit Zeta 1	Protein Coding	16.74	DISEASES inferred ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)
6	ERLIN2	ER Lipid Raft Associated 2	Protein Coding	16.48	DISEASES inferred ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)
7	SPAST	Spastin	Protein Coding	16.45	DISEASES inferred ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)
8	KIF5A	Kinesin Family Member 5A	Protein Coding	16.42	DISEASES inferred ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)

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Variations for Spastic Paraplegia 12, Autosomal Dominant

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 12, Autosomal Dominant:

⁷⁵

#	Symbol	AA change	Variation ID	SNP ID
1	RTN2	p.Ser367Phe	VAR_067562	rs140494585

ClinVar genetic disease variations for Spastic Paraplegia 12, Autosomal Dominant:

⁶

#	Gene	Variation	Type	Significance	SNP ID	Assembly	Location
1	RTN2	RTN2, 1-BP INS, 178C	insertion	Pathogenic
2	RTN2	RTN2, DEL	deletion	Pathogenic
3	RTN2	NM_005619.4(RTN2): c.1100C> T (p.Ser367Phe)	single nucleotide variant	Pathogenic	rs140494585	GRCh37	Chromosome 19, 45992745: 45992745
4	RTN2	NM_005619.4(RTN2): c.1100C> T (p.Ser367Phe)	single nucleotide variant	Pathogenic	rs140494585	GRCh38	Chromosome 19, 45489487: 45489487
5	RTN2	NM_005619.4(RTN2): c.939delT (p.Thr314Leufs)	deletion	Pathogenic	rs768449676	GRCh37	Chromosome 19, 45996512: 45996512
6	RTN2	NM_005619.4(RTN2): c.939delT (p.Thr314Leufs)	deletion	Pathogenic	rs768449676	GRCh38	Chromosome 19, 45493254: 45493254

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Expression for Spastic Paraplegia 12, Autosomal Dominant

Search GEO for disease gene expression data for Spastic Paraplegia 12, Autosomal Dominant.

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Pathways for Spastic Paraplegia 12, Autosomal Dominant

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GO Terms for Spastic Paraplegia 12, Autosomal Dominant

Cellular components related to Spastic Paraplegia 12, Autosomal Dominant according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	endoplasmic reticulum	GO:0005783	9.63	ATL1 ERLIN2 REEP1 RTN2 SPAST ZFYVE27
2	endoplasmic reticulum membrane	GO:0005789	9.43	ATL1 ERLIN2 REEP1 RTN2 SPAST ZFYVE27
3	integral component of endoplasmic reticulum membrane	GO:0030176	9.26	RTN2 ZFYVE27
4	endoplasmic reticulum tubular network	GO:0071782	8.8	ATL1 REEP1 ZFYVE27

Biological processes related to Spastic Paraplegia 12, Autosomal Dominant according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	axonogenesis	GO:0007409	8.62	ATL1 SPAST

Molecular functions related to Spastic Paraplegia 12, Autosomal Dominant according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	microtubule binding	GO:0008017	8.8	KIF5A REEP1 SPAST

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Sources for Spastic Paraplegia 12, Autosomal Dominant

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⁴¹ MalaCards

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⁵⁷ OMIM

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⁵⁹ Orphanet

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⁶¹ PharmGKB

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⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

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⁷⁰ SNOMED-CT via Orphanet

⁷¹ TGDB

⁷² Tocris

⁷³ UMLS

⁷⁴ UMLS via Orphanet

⁷⁵ UniProtKB/Swiss-Prot

⁷⁶ Wikipedia