Spastic Paraplegia 9a, Autosomal Dominant disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

SPG9A MCID: SPS158 MIFTS: 44	Spastic Paraplegia 9a, Autosomal Dominant (SPG9A) Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases
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Aliases & Classifications for Spastic Paraplegia 9a, Autosomal Dominant

MalaCards integrated aliases for Spastic Paraplegia 9a, Autosomal Dominant:

Name: Spastic Paraplegia 9a, Autosomal Dominant ⁵⁶ ⁷³

Hereditary Spastic Paraplegia 9a ¹² ²⁹ ⁶ ¹⁵

Spg9a ⁵⁶ ¹² ⁷³

Cataracts with Motor Neuronopathy, Short Stature, and Skeletal Abnormalities ⁵⁶ ⁷³

Spastic Paraparesis-Amyopathy-Cataracts-Gastroesophageal Reflux Syndrome ¹² ⁵⁸

Ad-Spg9a ¹² ⁵⁸

Spastic Paraparesis with Amyotrophy, Cataracts, and Gastroesophageal Reflux ⁵⁶

Cataracts with Motor Neuronopathy, Short Stature and Skeletal Abnormalities ¹²

Spastic Paraparesis with Amyopathy, Cataracts, and Gastroesophageal Reflux ⁷³

Spastic Paraparesis with Amyopathy, Cataracts and Gastroesophageal Reflux ¹²

Cataracts Motor Neuropathy-Short Stature-Skeletal Anomalies Syndrome ¹²

Cataracts-Motor Neuropathy-Short Stature-Skeletal Anomalies Syndrome ⁵⁸

Autosomal Dominant Complex Spastic Paraplegia Type 9a ¹²

Autosomal Dominant Spastic Paraplegia Type 9a ⁵⁸

Autosomal Dominant Spastic Paraplegia 9a ¹²

Spastic Paraplegia 9, Autosomal Dominant ⁷¹

Characteristics:

Orphanet epidemiological data:

⁵⁸

autosomal dominant spastic paraplegia type 9a
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult,Infancy;

OMIM:

⁵⁶

Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
variable age of onset (first to third decades)
weakness during pregnancy in some affected females has been reported

HPO:

³¹

spastic paraplegia 9a, autosomal dominant:
Inheritance autosomal dominant inheritance genetic anticipation
Onset and clinical course slow progression

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Neuronal diseases Eye diseases Gastrointestinal diseases Skin diseases Respiratory diseases Bone diseases Nephrological diseases Ear diseases Mental diseases

See all MalaCards categories (disease lists)

ICD10: ³² ³³

Diseases of the nervous system

Systemic atrophies primarily affecting the central nervous system

Hereditary ataxia

Hereditary spastic paraplegia

Orphanet: ⁵⁸

Rare neurological diseases

Rare eye diseases

External Ids:

Disease Ontology ¹² DOID:0110824

OMIM ⁵⁶ 601162

OMIM Phenotypic Series ⁵⁶ PS303350

MeSH ⁴³ D015419

ICD10 ³² G11.4

ICD10 via Orphanet ³³ G11.4

Orphanet ⁵⁸ ORPHA447753

MedGen ⁴¹ C1832669

UMLS ⁷¹ C1832669

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Summaries for Spastic Paraplegia 9a, Autosomal Dominant

UniProtKB/Swiss-Prot : ⁷³ Spastic paraplegia 9A, 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. SPG9A patients have gait difficulties, motor neuropathy, and dysarthria. Additional variable features include cerebellar signs, cataract, pes cavus, and urinary urgency.

MalaCards based summary : Spastic Paraplegia 9a, Autosomal Dominant, also known as hereditary spastic paraplegia 9a, is related to cutis laxa and autosomal recessive cutis laxa type iii, and has symptoms including upper motor neuron signs An important gene associated with Spastic Paraplegia 9a, Autosomal Dominant is ALDH18A1 (Aldehyde Dehydrogenase 18 Family Member A1), and among its related pathways/superpathways are Carbon metabolism and Amino Acid metabolism. Affiliated tissues include bone, eye and cerebellum, and related phenotypes are spastic gait and lower limb hyperreflexia

Disease Ontology : ¹² A hereditary spastic paraplegia that has material basis in autosomal dominant heterozygous mutation in the ALDH18A1 gene on chromosome 10q24.

OMIM : ⁵⁶ Autosomal dominant spastic paraplegia-9A is a neurologic disorder characterized by onset of slowly progressive spasticity mainly affecting the lower limbs. The age at onset usually ranges from adolescence to adulthood, and patients have gait difficulties, motor neuropathy, and dysarthria. Additional variable features include cerebellar signs, cataract, pes cavus, and urinary urgency (summary by Coutelier et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600). (601162)

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Related Diseases for Spastic Paraplegia 9a, 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, 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
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 9a, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)

#	Related Disease	Score	Top Affiliating Genes
1	cutis laxa	9.9	PYCR1 ALDH18A1
2	autosomal recessive cutis laxa type iii	9.9	PYCR1 ALDH18A1
3	autosomal recessive cutis laxa type i	9.9	PYCR1 ALDH18A1
4	cutis laxa, autosomal recessive, type iiib	9.9	PYCR1 ALDH18A1
5	cutis laxa, autosomal recessive, type ib	9.9	PYCR1 ALDH18A1
6	cutis laxa, autosomal recessive, type iia	9.9	PYCR1 ALDH18A1
7	cutis laxa, autosomal recessive, type iiia	9.9	PYCR1 ALDH18A1
8	borderline glaucoma	9.8	PYCR3 PYCR1
9	cutis laxa, autosomal recessive, type ic	9.8	PYCR1 ALDH18A1
10	cutis laxa, autosomal recessive, type ia	9.8	PYCR1 ALDH18A1
11	hyperornithinemia-hyperammonemia-homocitrullinuria syndrome	9.8	OTC ALDH18A1
12	autosomal recessive cutis laxa type ii classic type	9.7	PYCR1 ALDH18A1
13	leukodystrophy, hypomyelinating, 10	9.7	PYCR3 PYCR1
14	neu-laxova syndrome 2	9.6	PYCR1 ALDH18A1
15	cutis laxa, autosomal recessive, type iib	9.5	PYCR3 PYCR1 ALDH18A1
16	hyperprolinemia	9.5	PYCR3 PYCR1 ALDH18A1
17	geroderma osteodysplasticum	9.5	PYCR1 ALDH18A1
18	spastic paraplegia 9b, autosomal recessive	8.2	PYCR3 PYCR1 PPP2R3C OTC GDAP1 ALDH18A1

Graphical network of the top 20 diseases related to Spastic Paraplegia 9a, Autosomal Dominant:

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Symptoms & Phenotypes for Spastic Paraplegia 9a, Autosomal Dominant

Human phenotypes related to Spastic Paraplegia 9a, Autosomal Dominant:

⁵⁸ ³¹ (show top 50) (show all 56)

#	Description	HPO Frequency	Orphanet Frequency	HPO Source Accession
1	spastic gait ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0002064
2	lower limb hyperreflexia ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0002395
3	hyperreflexia in upper limbs ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0007350
4	pes cavus ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0001761
5	babinski sign ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0003487
6	abnormality of pain sensation ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0010832
7	lower limb hypertonia ⁵⁸ ³¹	frequent (33%)	Frequent (79-30%)	HP:0006895
8	sensorineural hearing impairment ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000407
9	muscle weakness ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001324
10	tremor ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001337
11	memory impairment ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002354
12	mitral regurgitation ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001653
13	psychosis ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000709
14	abnormal cerebellum morphology ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0001317
15	dementia ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000726
16	muscle spasm ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0003394
17	anarthria ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002425
18	urinary incontinence ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000020
19	developmental cataract ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000519
20	horizontal nystagmus ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000666
21	pollakisuria ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0100515
22	postural instability ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002172
23	urinary urgency ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0000012
24	spastic dysarthria ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002464
25	corpus callosum atrophy ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0007371
26	falls ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002527
27	impaired vibration sensation in the lower limbs ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002166
28	lower limb pain ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0012514
29	enlarged cisterna magna ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0002280
30	low back pain ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0003419
31	abnormality of the dorsal column of the spinal cord ⁵⁸ ³¹	occasional (7.5%)	Occasional (29-5%)	HP:0011397
32	nystagmus ³¹	occasional (7.5%)		HP:0000639
33	impaired vibratory sensation ³¹	occasional (7.5%)		HP:0002495
34	seizure ³¹	occasional (7.5%)		HP:0001250
35	cataract ³¹			HP:0000518
36	delayed skeletal maturation ³¹			HP:0002750
37	seizures ⁵⁸		Occasional (29-5%)
38	short stature ³¹			HP:0004322
39	gastroesophageal reflux ³¹			HP:0002020
40	vomiting ³¹			HP:0002013
41	gait disturbance ³¹			HP:0001288
42	abnormal pyramidal sign ⁵⁸		Frequent (79-30%)
43	hyperreflexia ³¹			HP:0001347
44	specific learning disability ³¹			HP:0001328
45	dysarthria ³¹			HP:0001260
46	abnormality of pelvic girdle bone morphology ³¹			HP:0002644
47	dysfunction of lateral corticospinal tracts ³¹			HP:0007299
48	spastic paraplegia ³¹			HP:0001258
49	hiatus hernia ³¹			HP:0002036
50	abnormality of the cerebral white matter ⁵⁸		Occasional (29-5%)

Symptoms via clinical synopsis from OMIM:

⁵⁶

Neurologic Central Nervous System:
hypertonia
hyperreflexia
dysarthria
dysfunction of lateral corticospinal tracts
lower limb spasticity
more

Head And Neck Eyes:
nystagmus (in some patients)
cataracts (in some patients)

Abdomen Gastrointestinal:
hiatal hernia (in some patients)
gastroesophageal reflux (in some patients)
vomiting (in some patients)

Genitourinary Bladder:
urinary urgency (in some patients)
urinary incontinence (in some patients)

Skeletal Skull:
dysplastic skull base (in some patients)

Skeletal Hands:
small carpal bones (in some patients)

Laboratory Abnormalities:
low plasma levels of citrulline, ornithine, proline, and arginine

Muscle Soft Tissue:
generalized amyotrophy

Growth Height:
short stature (in some patients)

Skeletal Feet:
pes cavus (in some patients)

Skeletal:
delayed bone age (in some patients)

Skeletal Pelvis:
dysplastic hips (in some patients)

Neurologic Peripheral Nervous System:
motor polyneuropathy (in some patients)
decreased vibration sense (in some patients)

Clinical features from OMIM:

601162

UMLS symptoms related to Spastic Paraplegia 9a, Autosomal Dominant:

upper motor neuron signs

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Drugs & Therapeutics for Spastic Paraplegia 9a, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 9a, Autosomal Dominant

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Genetic Tests for Spastic Paraplegia 9a, Autosomal Dominant

Genetic tests related to Spastic Paraplegia 9a, Autosomal Dominant:

#	Genetic test	Affiliating Genes
1	Hereditary Spastic Paraplegia 9a ²⁹	ALDH18A1

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Anatomical Context for Spastic Paraplegia 9a, Autosomal Dominant

MalaCards organs/tissues related to Spastic Paraplegia 9a, Autosomal Dominant:

⁴⁰

Bone, Eye, Cerebellum, Spinal Cord

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Publications for Spastic Paraplegia 9a, Autosomal Dominant

Articles related to Spastic Paraplegia 9a, Autosomal Dominant:

#	Title	Authors	PMID	Year
1	ALDH18A1 gene mutations cause dominant spastic paraplegia SPG9: loss of function effect and plausibility of a dominant negative mechanism. ⁵⁶ ⁶	Panza E...Seri M	26297558	2016
2	Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. ⁵⁶ ⁶	Coutelier M...Stevanin G	26026163	2015
3	Genetic mapping to 10q23.3-q24.2, in a large Italian pedigree, of a new syndrome showing bilateral cataracts, gastroesophageal reflux, and spastic paraparesis with amyotrophy. ⁵⁶ ⁶	Seri M...Devoto M	9973297	1999
4	Cataracts, motor system disorder, short stature, learning difficulties, and skeletal abnormalities: a new syndrome? ⁵⁶ ⁶	Slavotinek AM...Hurst JA	8779323	1996
5	Hereditary Spastic Paraplegia Overview ⁶	Hedera P	20301682	2000
6	Δ1 -Pyrroline-5-carboxylate synthetase deficiency: An emergent multifaceted urea cycle-related disorder. ⁶¹	Marco-Marin C...Rubio V	32017139	2020
7	P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9. ⁶¹	Magini P...Panza E	31402623	2019
8	Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment. ⁶¹	Koh K...Japan Spastic Paraplegia Research Consortium	29915212	2018

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Genes for Spastic Paraplegia 9a, Autosomal Dominant

Genes related to Spastic Paraplegia 9a, Autosomal Dominant (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	ALDH18A1	Aldehyde Dehydrogenase 18 Family Member A1	Protein Coding	1676.29	Molecular basis known ⁵⁶ Pathogenic ⁶ Causative germline mutation (loss of function) ⁵⁸ Causative variation ⁷³ Genetic Tests ²⁹ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)	9973297 26297558 8779323 (more) 26026163
2	PPP2R3C	Protein Phosphatase 2 Regulatory Subunit B''Gamma	Protein Coding	7.28	DISEASES inferred ¹⁵
3	OTC	Ornithine Carbamoyltransferase	Protein Coding	6.29	DISEASES inferred ¹⁵
4	PYCR1	Pyrroline-5-Carboxylate Reductase 1	Protein Coding	6.01	DISEASES inferred ¹⁵
5	GDAP1	Ganglioside Induced Differentiation Associated Protein 1	Protein Coding	5.96	DISEASES inferred ¹⁵
6	PYCR3	Pyrroline-5-Carboxylate Reductase 3	Protein Coding	5.85	DISEASES inferred ¹⁵

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Variations for Spastic Paraplegia 9a, Autosomal Dominant

ClinVar genetic disease variations for Spastic Paraplegia 9a, Autosomal Dominant:

⁶ (show top 50) (show all 60) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	GRCh37 Pos	GRCh38 Pos
1	ALDH18A1	NM_002860.4(ALDH18A1):c.727G>C (p.Val243Leu)	SNV	Pathogenic	217116	rs864321669	10:97392797-97392797	10:95633040-95633040
2	ALDH18A1	NM_002860.4(ALDH18A1):c.359T>C (p.Val120Ala)	SNV	Pathogenic	217118	rs863224945	10:97397138-97397138	10:95637381-95637381
3	ALDH18A1	NM_002860.4(ALDH18A1):c.1994G>T (p.Arg665Leu)	SNV	Pathogenic	217119	rs766264810	10:97371129-97371129	10:95611372-95611372
4	ALDH18A1	NM_002860.4(ALDH18A1):c.88+1G>A	SNV	Likely pathogenic	659530		10:97413046-97413046	10:95653289-95653289
5	ALDH18A1	NM_002860.4(ALDH18A1):c.1314C>T (p.Ile438=)	SNV	Conflicting interpretations of pathogenicity	444231	rs150526956	10:97380941-97380941	10:95621184-95621184
6	ALDH18A1	NM_002860.4(ALDH18A1):c.755G>A (p.Arg252Gln)	SNV	Conflicting interpretations of pathogenicity	217117	rs864321670	10:97392769-97392769	10:95633012-95633012
7	ALDH18A1	NM_002860.4(ALDH18A1):c.1740C>T (p.Ser580=)	SNV	Conflicting interpretations of pathogenicity	301763	rs139035272	10:97373784-97373784	10:95614027-95614027
8	ALDH18A1	NM_002860.4(ALDH18A1):c.1308G>A (p.Leu436=)	SNV	Conflicting interpretations of pathogenicity	301768	rs144816455	10:97380947-97380947	10:95621190-95621190
9	ALDH18A1	NM_002860.4(ALDH18A1):c.492C>T (p.Ala164=)	SNV	Conflicting interpretations of pathogenicity	301775	rs150472102	10:97396916-97396916	10:95637159-95637159
10	ALDH18A1	NM_002860.4(ALDH18A1):c.2232G>A (p.Ser744=)	SNV	Conflicting interpretations of pathogenicity	391463	rs148601288	10:97366675-97366675	10:95606918-95606918
11	ALDH18A1	NM_002860.4(ALDH18A1):c.2160C>T (p.Phe720=)	SNV	Conflicting interpretations of pathogenicity	392692	rs374052426	10:97370000-97370000	10:95610243-95610243
12	ALDH18A1	NM_002860.4(ALDH18A1):c.2140G>A (p.Val714Ile)	SNV	Uncertain significance	862391		10:97370020-97370020	10:95610263-95610263
13	ALDH18A1	NM_002860.4(ALDH18A1):c.1199G>A (p.Arg400His)	SNV	Uncertain significance	862839		10:97385166-97385166	10:95625409-95625409
14	ALDH18A1	NM_002860.4(ALDH18A1):c.1073C>T (p.Pro358Leu)	SNV	Uncertain significance	862860		10:97387204-97387204	10:95627447-95627447
15	ALDH18A1	NM_002860.4(ALDH18A1):c.959A>G (p.Gln320Arg)	SNV	Uncertain significance	854542		10:97387318-97387318	10:95627561-95627561
16	ALDH18A1	NM_002860.4(ALDH18A1):c.887C>A (p.Thr296Lys)	SNV	Uncertain significance	860228		10:97388171-97388171	10:95628414-95628414
17	ALDH18A1	NM_002860.4(ALDH18A1):c.164G>A (p.Arg55His)	SNV	Uncertain significance	863417		10:97402888-97402888	10:95643131-95643131
18	ALDH18A1	NM_002860.4(ALDH18A1):c.87T>G (p.Ser29=)	SNV	Uncertain significance	834810		10:97413048-97413048	10:95653291-95653291
19	ALDH18A1	NM_002860.4(ALDH18A1):c.1867G>A (p.Asp623Asn)	SNV	Uncertain significance	424961	rs770815414	10:97373555-97373555	10:95613798-95613798
20	ALDH18A1	NM_002860.4(ALDH18A1):c.551C>T (p.Ala184Val)	SNV	Uncertain significance	464042	rs201428777	10:97396857-97396857	10:95637100-95637100
21	ALDH18A1	NM_002860.4(ALDH18A1):c.1777A>G (p.Ser593Gly)	SNV	Uncertain significance	464040	rs1231068982	10:97373747-97373747	10:95613990-95613990
22	ALDH18A1	NM_002860.4(ALDH18A1):c.868G>A (p.Gly290Arg)	SNV	Uncertain significance	464043	rs368147360	10:97388190-97388190	10:95628433-95628433
23	ALDH18A1	NM_002860.4(ALDH18A1):c.1264C>G (p.Leu422Val)	SNV	Uncertain significance	464038	rs142712849	10:97380991-97380991	10:95621234-95621234
24	ALDH18A1	NM_002860.4(ALDH18A1):c.1015G>A (p.Val339Ile)	SNV	Uncertain significance	464037	rs1346763871	10:97387262-97387262	10:95627505-95627505
25	ALDH18A1	NM_002860.4(ALDH18A1):c.1201G>A (p.Asp401Asn)	SNV	Uncertain significance	517143	rs1242600175	10:97385164-97385164	10:95625407-95625407
26	ALDH18A1	NM_002860.4(ALDH18A1):c.1604T>A (p.Leu535Gln)	SNV	Uncertain significance	532701	rs200452017	10:97376235-97376235	10:95616478-95616478
27	ALDH18A1	NM_002860.4(ALDH18A1):c.428C>T (p.Ser143Leu)	SNV	Uncertain significance	581031	rs1302919102	10:97397069-97397069	10:95637312-95637312
28	ALDH18A1	NM_002860.4(ALDH18A1):c.1393G>C (p.Glu465Gln)	SNV	Uncertain significance	579657	rs757876226	10:97380862-97380862	10:95621105-95621105
29	ALDH18A1	NM_002860.4(ALDH18A1):c.2231C>T (p.Ser744Leu)	SNV	Uncertain significance	581547	rs762271422	10:97366676-97366676	10:95606919-95606919
30	ALDH18A1	NM_002860.4(ALDH18A1):c.1233G>T (p.Leu411Phe)	SNV	Uncertain significance	578899	rs758828421	10:97385132-97385132	10:95625375-95625375
31	ALDH18A1	NM_002860.4(ALDH18A1):c.1078+4A>G	SNV	Uncertain significance	578302	rs1566018543	10:97387195-97387195	10:95627438-95627438
32	ALDH18A1	NM_002860.4(ALDH18A1):c.709G>C (p.Gly237Arg)	SNV	Uncertain significance	573157	rs201841420	10:97393256-97393256	10:95633499-95633499
33	ALDH18A1	NM_002860.4(ALDH18A1):c.598C>T (p.Arg200Cys)	SNV	Uncertain significance	570966	rs201801058	10:97393367-97393367	10:95633610-95633610
34	ALDH18A1	NM_002860.4(ALDH18A1):c.1370G>A (p.Arg457His)	SNV	Uncertain significance	575749	rs570730665	10:97380885-97380885	10:95621128-95621128
35	ALDH18A1	NM_002860.4(ALDH18A1):c.847C>T (p.Leu283Phe)	SNV	Uncertain significance	566189	rs747291828	10:97388211-97388211	10:95628454-95628454
36	ALDH18A1	NM_002860.4(ALDH18A1):c.2383A>G (p.Asn795Asp)	SNV	Uncertain significance	665168		10:97366524-97366524	10:95606767-95606767
37	ALDH18A1	NM_002860.4(ALDH18A1):c.2276C>T (p.Thr759Ile)	SNV	Uncertain significance	664573		10:97366631-97366631	10:95606874-95606874
38	ALDH18A1	NM_002860.4(ALDH18A1):c.2077A>G (p.Ser693Gly)	SNV	Uncertain significance	658085		10:97371046-97371046	10:95611289-95611289
39	ALDH18A1	NM_002860.4(ALDH18A1):c.1865G>A (p.Arg622Gln)	SNV	Uncertain significance	658959		10:97373557-97373557	10:95613800-95613800
40	ALDH18A1	NM_002860.4(ALDH18A1):c.1237G>A (p.Glu413Lys)	SNV	Uncertain significance	647291		10:97385128-97385128	10:95625371-95625371
41	ALDH18A1	NM_002860.4(ALDH18A1):c.709G>T (p.Gly237Trp)	SNV	Uncertain significance	638826		10:97393256-97393256	10:95633499-95633499
42	ALDH18A1	NM_002860.4(ALDH18A1):c.169C>A (p.His57Asn)	SNV	Uncertain significance	660899		10:97402883-97402883	10:95643126-95643126
43	ALDH18A1	NM_002860.4(ALDH18A1):c.678C>T (p.Val226=)	SNV	Likely benign	464041	rs772829720	10:97393287-97393287	10:95633530-95633530
44	ALDH18A1	NM_002860.4(ALDH18A1):c.2111-7C>A	SNV	Likely benign	513428	rs542177817	10:97370056-97370056	10:95610299-95610299
45	ALDH18A1	NM_002860.4(ALDH18A1):c.1568C>T (p.Ala523Val)	SNV	Likely benign	464039	rs529294368	10:97376271-97376271	10:95616514-95616514
46	ALDH18A1	NM_002860.4(ALDH18A1):c.1253T>A (p.Leu418His)	SNV	Likely benign	706650		10:97381002-97381002	10:95621245-95621245
47	ALDH18A1	NM_002860.4(ALDH18A1):c.948C>T (p.Leu316=)	SNV	Likely benign	702588		10:97387329-97387329	10:95627572-95627572
48	ALDH18A1	NM_002860.4(ALDH18A1):c.219C>T (p.Ile73=)	SNV	Likely benign	791719		10:97402833-97402833	10:95643076-95643076
49	ALDH18A1	NM_002860.4(ALDH18A1):c.75C>T (p.Thr25=)	SNV	Likely benign	784762		10:97413060-97413060	10:95653303-95653303
50	ALDH18A1	NM_002860.4(ALDH18A1):c.1635T>C (p.Leu545=)	SNV	Likely benign	713650		10:97373889-97373889	10:95614132-95614132

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 9a, Autosomal Dominant:

⁷³

#	Symbol	AA change	Variation ID	SNP ID
1	ALDH18A1	p.Val120Ala	VAR_075885	rs863224945
2	ALDH18A1	p.Val243Leu	VAR_075890	rs864321669
3	ALDH18A1	p.Arg252Gln	VAR_075891	rs864321670
4	ALDH18A1	p.Ser652Phe	VAR_075893
5	ALDH18A1	p.Arg665Leu	VAR_075894	rs766264810

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Expression for Spastic Paraplegia 9a, Autosomal Dominant

Search GEO for disease gene expression data for Spastic Paraplegia 9a, Autosomal Dominant.

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Pathways for Spastic Paraplegia 9a, Autosomal Dominant

Pathways related to Spastic Paraplegia 9a, Autosomal Dominant according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	Carbon metabolism ³⁶ Show member pathways 2-Oxocarboxylic acid metabolism ³⁶ Biosynthesis of amino acids ³⁶ formaldehyde oxidation ¹	11.58	PYCR3 PYCR1 OTC ALDH18A1
2	Amino Acid metabolism ¹	11.46	PYCR1 OTC ALDH18A1
3	Arginine and proline metabolism ³⁶ Show member pathways 4-hydroxyproline degradation ¹ Agmatine biosynthesis ⁶⁵ putrescine biosynthesis II ¹	11.19	PYCR3 PYCR1 ALDH18A1
4	Amino acid synthesis and interconversion (transamination) ⁶⁵ Show member pathways asparagine biosynthesis ¹ L-cysteine degradation II ¹ Serine biosynthesis ⁶⁵	10.96	PYCR3 PYCR1 ALDH18A1
5	Urea cycle and metabolism of amino groups ¹ Show member pathways proline biosynthesis ¹ putrescine biosynthesis I ¹ spermine biosynthesis ¹	10.3	PYCR3 PYCR1 OTC ALDH18A1

Sources

GO Terms for Spastic Paraplegia 9a, Autosomal Dominant

Cellular components related to Spastic Paraplegia 9a, Autosomal Dominant according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	mitochondrion	GO:0005739	8.92	PYCR1 OTC GDAP1 ALDH18A1

Biological processes related to Spastic Paraplegia 9a, Autosomal Dominant according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	oxidation-reduction process	GO:0055114	9.5	PYCR3 PYCR1 ALDH18A1
2	L-proline biosynthetic process	GO:0055129	9.33	PYCR3 PYCR1 ALDH18A1
3	citrulline biosynthetic process	GO:0019240	9.26	OTC ALDH18A1
4	proline biosynthetic process	GO:0006561	9.13	PYCR3 PYCR1 ALDH18A1
5	cellular amino acid biosynthetic process	GO:0008652	8.92	PYCR3 PYCR1 OTC ALDH18A1

Molecular functions related to Spastic Paraplegia 9a, Autosomal Dominant according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	oxidoreductase activity	GO:0016491	9.33	PYCR3 PYCR1 ALDH18A1
2	identical protein binding	GO:0042802	9.26	PYCR3 PYCR1 OTC ALDH18A1
3	pyrroline-5-carboxylate reductase activity	GO:0004735	8.62	PYCR3 PYCR1

Sources

Sources for Spastic Paraplegia 9a, Autosomal Dominant

¹ BioSystems

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⁵⁶ OMIM

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⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

Spastic Paraplegia 9a, Autosomal Dominant (SPG9A)

Aliases & Classifications for Spastic Paraplegia 9a, Autosomal Dominant

MalaCards integrated aliases for Spastic Paraplegia 9a, Autosomal Dominant:

Characteristics:

Orphanet epidemiological data:

OMIM:

HPO:

Classifications:

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Summaries for Spastic Paraplegia 9a, Autosomal Dominant

Related Diseases for Spastic Paraplegia 9a, Autosomal Dominant

Diseases in the Spastic Paraplegia 3a family:

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Graphical network of the top 20 diseases related to Spastic Paraplegia 9a, Autosomal Dominant:

Symptoms & Phenotypes for Spastic Paraplegia 9a, Autosomal Dominant

Human phenotypes related to Spastic Paraplegia 9a, Autosomal Dominant:

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Variations for Spastic Paraplegia 9a, Autosomal Dominant

ClinVar genetic disease variations for Spastic Paraplegia 9a, Autosomal Dominant:

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 9a, Autosomal Dominant:

Expression for Spastic Paraplegia 9a, Autosomal Dominant

Pathways for Spastic Paraplegia 9a, Autosomal Dominant

Pathways related to Spastic Paraplegia 9a, Autosomal Dominant according to GeneCards Suite gene sharing:

GO Terms for Spastic Paraplegia 9a, Autosomal Dominant

Cellular components related to Spastic Paraplegia 9a, Autosomal Dominant according to GeneCards Suite gene sharing:

Biological processes related to Spastic Paraplegia 9a, Autosomal Dominant according to GeneCards Suite gene sharing:

Molecular functions related to Spastic Paraplegia 9a, Autosomal Dominant according to GeneCards Suite gene sharing:

Sources for Spastic Paraplegia 9a, Autosomal Dominant