ALDH18A1 - aldehyde dehydrogenase 18 family member A1 Gene

Homo sapiens

Also known as GSAS; P5CS; PYCS; SPG9; ADCL3; SPG9A; SPG9B; ARCL3A

Gene ID: 5832 | Gene type: protein coding

About ALDH18A1

Cytogenetic location: 10q24.1 Genomic coordinates (GRCh38): 10:95,605,941-95,656,711 (from NCBI)

This gene has 5 transcripts (splice variants), 261 orthologues and is associated with 14 phenotypes. Ubiquitous expression in duodenum (RPKM 41.4), small intestine (RPKM 34.7) and 25 other tissues.

Summary

This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial Enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]

ALDH18A1 Products(10)

mRNA	Protein	Name
NM_001017423.2	NP_001017423.1	delta-1-pyrroline-5-carboxylate synthase isoform 2
NM_001323412.2	NP_001310341.1	delta-1-pyrroline-5-carboxylate synthase isoform 3
NM_001323413.2	NP_001310342.1	delta-1-pyrroline-5-carboxylate synthase isoform 1
NM_001323414.2	NP_001310343.1	delta-1-pyrroline-5-carboxylate synthase isoform 1
NM_001323415.2	NP_001310344.1	delta-1-pyrroline-5-carboxylate synthase isoform 2
NM_001323416.2	NP_001310345.1	delta-1-pyrroline-5-carboxylate synthase isoform 3
NM_001323417.2	NP_001310346.1	delta-1-pyrroline-5-carboxylate synthase isoform 4
NM_001323418.2	NP_001310347.1	delta-1-pyrroline-5-carboxylate synthase isoform 5
NM_001323419.2	NP_001310348.1	delta-1-pyrroline-5-carboxylate synthase isoform 6
NM_002860.4	NP_002851.2	delta-1-pyrroline-5-carboxylate synthase isoform 1

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	Reference	Source
enables glutamate 5-kinase activity	IDA IDA: Inferred from direct assay	11092761	GOA
enables glutamate 5-kinase activity	IMP IMP: Inferred from mutant phenotype	26297558	GOA
enables glutamate-5-semialdehyde dehydrogenase activity	IDA IDA: Inferred from direct assay	11092761	GOA
enables glutamate-5-semialdehyde dehydrogenase activity	IMP IMP: Inferred from mutant phenotype	26297558	GOA
enables identical protein binding	IDA IDA: Inferred from direct assay	26297558	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	25416956	GOA

Biological Process GO Annotation	Evidence	Reference	Source
involved in citrulline biosynthetic process	IMP IMP: Inferred from mutant phenotype	11092761	GOA
involved in glutamate metabolic process	IMP IMP: Inferred from mutant phenotype	11092761	GOA
involved in ornithine biosynthetic process	IMP IMP: Inferred from mutant phenotype	11092761	GOA
involved in proline biosynthetic process	IMP IMP: Inferred from mutant phenotype	11092761	GOA

Cellular Component GO Annotation	Evidence	Reference	Source
located in mitochondrion	IDA IDA: Inferred from direct assay	26297558	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

ALDH18A1 Protein Structure

AA_kinase

Aldedh

0
200
400
600
795 a.a.

Protein Preferred Names

Protein Names

delta-1-pyrroline-5-carboxylate synthase

Spastic paraplegia-9 (spastic paraparesis with amyotrophy, cataracts and gastroesophageal reflux)

Related Diseases

Diseases

Alias

Spastic Paraplegia 9a, Autosomal Dominant

Hereditary Spastic Paraplegia 9a	SPG9A
Cataracts With Motor Neuronopathy, Short Stature, And Skeletal Abnormalities	Ad-Spg9a
Spastic Paraparesis-Amyopathy-Cataracts-Gastroesophageal Reflux Syndrome	Spastic Paraparesis With Amyotrophy, Cataracts, And Gastroesophageal Reflux
Autosomal Dominant Complex Spastic Paraplegia Type 9a	Autosomal Dominant Spastic Paraplegia 9a
Cataracts Motor Neuropathy-Short Stature-Skeletal Anomalies Syndrome	Cataracts With Motor Neuronopathy, Short Stature And Skeletal Abnormalities
Spastic Paraparesis With Amyopathy, Cataracts And Gastroesophageal Reflux	Autosomal Dominant Spastic Paraplegia Type 9a
Cataracts-Motor Neuropathy-Short Stature-Skeletal Anomalies Syndrome	Spastic Paraparesis With Amyopathy, Cataracts, And Gastroesophageal Reflux
Spastic Paraplegia 9, Autosomal Dominant

Spastic Paraplegia 9b, Autosomal Recessive

SPG9B	Autosomal Recessive Complex Spastic Paraplegia Type 9b
Hereditary Spastic Paraplegia 9b	Autosomal Recessive Spastic Paraplegia 9b
Autosomal Recessive Spastic Paraplegia Type 9b	Ar-Spg9b

Cutis Laxa, Autosomal Recessive, Type Iiia

ARCL3A	De Barsy Syndrome A
Aldh18a1-Related De Barsy Syndrome	Progeroid Syndrome Of De Barsy
Autosomal Recessive Cutis Laxa Type Iiia	P5cs Deficiency
De Barsy Syndrome	Cutis Laxa, Corneal Clouding, And Mental Retardation
Delta-1-Pyrroline 5-Carboxylate Synthetase Deficiency	Neurocutaneous Syndrome, Bicknell Type
Cutis Laxa Corneal Clouding Mental Retardation	Progeroid Syndrome De Barsy Type
Cutis Laxa, Autosomal Recessive, 3a	Cutis Laxa Autosomal Recessive Type Iiia
Developmental Delay-Choreoathetosis-Joint Dislocation-Lax Skin	Neurocutaneous Syndrome Bicknell Type
Corneal Clouding Cutis Laxa Mental Retardation

Cutis Laxa, Autosomal Dominant 3

ADCL3	Autosomal Dominant Cutis Laxa 3
Cutis Laxa, Autosomal Dominant, 3

Autosomal Recessive Cutis Laxa Type Iii

De Barsy Syndrome	Cutis Laxa-Corneal Clouding-Intellectual Disability Syndrome
Progeroid Syndrome, De Barsy Type	Corneal Clouding, Cutis Laxa And Intellectual Disability
Cutis Laxa Growth Deficiency Syndrome	Progeroid Syndrome Of De Barsy

Spastic Paraplegia 9

Autosomal Dominant Spastic Paraparesis	Bilateral Cataracts, Gastroesophageal Reflux, And Spastic Paraparesis With Amyotrophy
Cataracts, Motor Neuronopathy, Short Stature And Skeletal Abnormalities	Spg9
Spastic Paraplegia 9, Autosomal Dominant

Autosomal Dominant Spastic Paraplegia Type 9b

Ad-Spg9b

Cutis Laxa, Autosomal Dominant 1

Cutis Laxa, Autosomal Dominant	Autosomal Dominant Cutis Laxa
ADCL1	Adcl
Autosomal Dominant Cutis Laxa 1	Cutis Laxa, Autosomal Dominant, 1
Cutis Laxa, Autosomal Dominant, Type 1

Spastic Paraplegia 5a, Autosomal Recessive

SPG5A	Hereditary Spastic Paraplegia 5a
Autosomal Recessive Spastic Paraplegia 5a	Autosomal Recessive Spastic Paraplegia Type 5a
Spastic Paraplegia 5a	Spastic Paraplegia Type 5a
Spastic Paraplegia Type 5a, Recessive	Autosomal Recessive Spastic Paraplegia
Spastic Paraplegia-5a	Paraplegia, Spastic, Autosomal Recessive, Type 5a

Cutis Laxa

Generalized Elastolysis	Loose Skin
Dermatolysis	Dermatomegaly
Cutis Laxa Syndrome

Hereditary Spastic Paraplegia

Familial Spastic Paraplegia	Hereditary Spastic Paraparesis
Strumpell-Lorrain Disease	Familial Spastic Paraparesis
Hsp	Spg
Strümpell-Lorrain Disease	Spastic Paraplegia, Hereditary
French Settlement Disease	Strumpell-Lorrain Syndrome
Fsp	Spastic Paraplegia, Familial
Spastic Paraplegia Hereditary	Spastic Paraplegia 3, Autosomal Dominant
Spastic Paraparesis	Hereditary Spastic Paralysis
Familial Spastic Paralysis	Hereditary Spastic Ataxia

Paraplegia

Paraplegia, Lower

Severe Or Complete Loss Of Motor Function In The Lower Extremities And Lower Portions Of The Trunk

Gastroesophageal Reflux

Gastroesophageal Reflux Disease	Gerd
GER	Gastroesophageal Reflux, Pediatric
Acid Reflux	Gastresophageal Reflux
Gastro-Esophageal Reflux	Gerd - Gastro-Esophageal Reflux Disease

Cutis Laxa, Autosomal Recessive, Type Iiib

ARCL3B	De Barsy Syndrome B
Pycr1-Related De Barsy Syndrome	Autosomal Recessive Cutis Laxa Type Iiib
Pycr1 Deficiency	Pyrroline-5-Carboxylate Reductase 1 Deficiency
Cutis Laxa, Autosomal Recessive, 3b	Cutis Laxa Autosomal Recessive Type Iiib
Cutis Laxa, Autosomal Recessive, Type 3b

Spastic Paraparesis

Congenital Nervous System Abnormality

Congenital Neurologic Anomaly

Congenital Nervous System Disorder

Cutis Laxa, Autosomal Recessive, Type Iib

ARCL2B	Cutis Laxa With Progeroid Features
Autosomal Recessive Cutis Laxa Type 2b	Autosomal Recessive Cutis Laxa Type Iib
Arcl2, Progeroid Type	Cutis Laxa, Autosomal Recessive Type 2b
Autosomal Recessive Cutis Laxa Type 2, Progeroid Type	Cutis Laxa, Autosomal Recessive, 2b
Cl Type Iib	Cutis Laxa Autosomal Recessive Type Iib
Cutis Laxa, Autosomal Recessive, Type 2b

Spastic Paraplegia 19, Autosomal Dominant

SPG19	Hereditary Spastic Paraplegia 19
Autosomal Dominant Spastic Paraplegia Type 19	Autosomal Dominant Spastic Paraplegia 19
Spastic Paraplegia 19	Spastic Paraplegia-19

Nervous System Disease

Abnormality Of The Nervous System	Nervous System Diseases
Nervous System Disorder

Cutis Laxa, Autosomal Recessive, Type Iid

ARCL2D	Autosomal Recessive Cutis Laxa Type Iid
Autosomal Recessive Cutis Laxa Type 2d	Cutis Laxa, Autosomal Recessive, 2d

Hyperprolinemia

Proline Oxidase Deficiency	Hyperprolinemia Type 1
Proline Hydrogenase Deficiency	Prolinemia
Pyrroline Carboxylate Dehydrogenase Deficiency	Pyrroline-5-Carboxylate Dehydrogenase Deficiency
Proline Dehydrogenase Deficiency	Hyperprolinemia Type 2

Spastic Paraplegia 34, X-Linked

SPG34	Hereditary Spastic Paraplegia 34
X-Linked Spastic Paraplegia Type 34	X-Linked Spastic Paraplegia 34

Spastic Paraplegia 14, Autosomal Recessive

SPG14	Hereditary Spastic Paraplegia 14
Autosomal Recessive Spastic Paraplegia Type 14	Autosomal Recessive Spastic Paraplegia 14
Spastic Paraplegia 14

Mend Syndrome

Male Ebp Disorder With Neurological Defects	MEND
Male Ebp Disorder With Neurologic Defects

Cutis Laxa, Autosomal Recessive, Type Iia

ARCL2A	Cutis Laxa With Joint Laxity And Retarded Development
Cutis Laxa With Growth And Developmental Delay	Cutis Laxa, Debre Type
Cutis Laxa With Bone Dystrophy	Arcl2
Cutis Laxa With Congenital Disorder Of Glycosylation	Autosomal Recessive Cutis Laxa Type Iia
Cutis Laxa, Autosomal Recessive Type 2a	Cutis Laxa, Autosomal Recessive, 2a
Cl Type Iia	Cutis Laxa Autosomal Recessive Type Iia

Cataract

Cataracts	Cat - [Cataract]
Cataract Form	Lens Opacity
Lens Opacities

Spastic Paraplegia 36, Autosomal Dominant

SPG36	Hereditary Spastic Paraplegia 36
Autosomal Dominant Spastic Paraplegia Type 36	Autosomal Dominant Spastic Paraplegia 36

Gamma-Amino Butyric Acid Metabolism Disorder

Disorder Of Gamma-Aminobutyric Acid Metabolism	Disorder Of Gaba Metabolism
Disorders Of Gaba - [Gamma Aminobutyric Acid] Metabolism

Geroderma Osteodysplasticum

Gerodermia Osteodysplastica	Geroderma Osteodysplastica
GO	Walt Disney Dwarfism
Type Of Gerodermia Osteodysplastica

Autosomal Recessive Cutis Laxa Type Ii Classic Type

Arcl2, Classic Type	Arcl2, Debre Type
Autosomal Recessive Cutis Laxa Type 2, Classic Type	Autosomal Recessive Cutis Laxa Type 2, Debre Type

Succinic Semialdehyde Dehydrogenase Deficiency

4-Hydroxybutyric Aciduria	Ssadh Deficiency
Gamma-Hydroxybutyric Aciduria	Gaba Metabolic Defect
SSADHD	Ssadh
Succinate-Semialdehyde Dehydrogenase Deficiency	Gamma-Hydroxybutyricaciduria
4-Hydroxybutyricaciduria	Gamma-Hydroxybutyric Acidemia
Succinate Semialdehyde Dehydrogenase Deficiency

Leukodystrophy, Hypomyelinating, 10

Hypomyelinating Leukodystrophy 10	HLD10
Pycr2-Related Microcephaly-Progressive Leukoencephalopathy	Leukodystrophy, Hypomyelinating, Type 10

Hyperprolinemia, Type Ii

Hyperprolinemia Type 2	HYRPRO2
Hpii	1-Pyrroline-5-Carboxylate Dehydrogenase Deficiency
Hyperprolinemia Type Ii	1 Alpha Pyrroline-5-Carboxylate Dehydrogenase Deficiency
Type 2 Hyperprolinemia	Delta-1-Pyrroline-5-Carboxylate Dehydrogenase Deficiency
Hyperprolinemia 2

Cutis Laxa, Autosomal Recessive, Type Ia

ARCL1A	Cutis Laxa, Autosomal Recessive
Autosomal Recessive Cutis Laxa Type Ia	Cutis Laxa, Autosomal Recessive, Type 1a
Arcl1	Cutis Laxa, Autosomal Recessive, 1a
Cl Type I	Cutis Laxa Autosomal Recessive Type I
Cutis Laxa Autosomal Recessive Type Ia	Cutis Laxa, Autosomal Recessive, Type I

Cutis Laxa, Autosomal Recessive, Type Ib

ARCL1B	Cutis Laxa, Autosomal Recessive, Type 1b
Autosomal Recessive Cutis Laxa Type Ib	Lethal Arteriopathy Syndrome Due To Fibulin-4 Deficiency
Cutis Laxa, Autosomal Recessive, 1b	Cutis Laxa Autosomal Recessive Type Ib

Cutis Laxa, Autosomal Recessive, Type Ic

Cutis Laxa With Severe Pulmonary, Gastrointestinal, And Urinary Abnormalities	ARCL1C
Urban-Rifkin-Davis Syndrome	Cutis Laxa With Severe Pulmonary, Gastrointestinal And Urinary Anomalies
URDS	Autosomal Recessive Cutis Laxa Type Ic
Autosomal Recessive Cutis Laxa Type 1c	Cutis Laxa With Severe Pulmonary Gastrointestinal And Urinary Abnormalities

Wrinkly Skin Syndrome

WSS	Wrinkled Skin Syndrome

Autosomal Recessive Cutis Laxa Type I

Autosomal Recessive Cutis Laxa Type 1	Cutis Laxa, Type 1
Cutis Laxa, Autosomal Recessive, Type I	Cutis Laxa, Autosomal Recessive Type 1
Cutis Laxa, Autosomal Recessive	Arcl1
Autosomal Recessive Cutis Laxa With Severe Systemic Involvement	Autosomal Recessive Cutis Laxa, Pulmonary Emphysema Type

Immunodeficiency 47

Congenital Disorder Of Glycosylation Type Ii	CDG2E
Congenital Disorder Of Glycosylation Type Iie	IMD47
Cdg2s	Cdg Iis
Cdgiis	Immunodeficiency And Hepatopathy With Or Without Neurologic Features
Congenital Disorder Of Glycosylation, Type Ii	CDG1I
Congenital Disorder Of Glycosylation, Type Iie	Cdg Iie
Congenital Disorder Of Glycosylation Type 2e	Congenital Disorder Of Glycosylation, Type Iis
Cdg Ii	Cdgii
Cdgiie	Carbohydrate Deficient Glycoprotein Syndrome Type Iie
Cdg Syndrome Type Iie	Congenital Disorder Of Glycosylation Ii
Congenital Disorder Of Glycosylation 1i	Cdg-Iie
Alg2-Cdg	Cdg-Ii
Glycosylation, Congenital Disorder Of, Type Ii	Cdgiide
Congenital Disorder Of Glycosylation Type Iis	Cog7-Cdg
Cdg Syndrome Type Ii	Carbohydrate Deficient Glycoprotein Syndrome Type Ii
Congenital Disorder Of Glycosylation Type 1i	Mannosyltransferase 2 Deficiency
Congenital Disorder Of Glycosylation 2e	Congenital Disorder Of Glycosylation 2s
Congenital Disorders Of Glycosylation Type Ii	Glycosylation, Congenital Disorder Of, Type Iie
Immunodeficiency, Type 47	Congenital Disorder Of Glycosylation Type 2a

Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Hhh Syndrome	Ornithine Translocase Deficiency
Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome	HHHS
Hhh	Triple H Syndrome
Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome	Ornithine Translocase Deficiency Syndrome
Hyperornithinaemia-Hyperammonaemia-Homocitrullinuria Syndrome	Ornt1 Deficiency
Ornithine Carrier Deficiency	Hyperornithinemia, Hyperammonemia, Homocitrullinuria Syndrome

Spastic Paraplegia 64, Autosomal Recessive

SPG64	Hereditary Spastic Paraplegia 64
Autosomal Recessive Spastic Paraplegia Type 64	Autosomal Recessive Spastic Paraplegia 64
Paraplegia, Spastic, Type 64, Autosomal Recessive

Spastic Paraplegia 8, Autosomal Dominant

SPG8	Hereditary Spastic Paraplegia 8
Autosomal Dominant Spastic Paraplegia Type 8	Autosomal Dominant Spastic Paraplegia 8
Paraplegia, Spastic, Autosomal Dominant, Type 8

Occipital Horn Syndrome

OHS	Eds Ix
Cutis Laxa X-Linked	Cutis Laxa, X-Linked
Cutis Laxa, X-Linked, Formerly	Ehlers-Danlos Syndrome, Occipital Horn Type, Formerly
Eds Ix, Formerly	Eds9, Formerly
Ehlers-Danlos Syndrome Type 9	Ehlers-Danlos Syndrome Type Ix
X-Linked Cutis Laxa	Ehlers-Danlos Syndrome, Occipital Horn Type
Eds9	Ehlers-Danlos Syndrome Occipital Horn Type

Argininemia

Hyperargininemia	Arginase Deficiency
Arg1 Deficiency	Arginase-1 Deficiency
Deficiency Of Canavanase	Arginase Deficiency Disease
ARGIN

Epilepsy, Pyridoxine-Dependent

Pyridoxine-Dependent Epilepsy	PDE
Pyridoxine Dependency With Seizures	Vitamin B6-Dependent Seizures
EPD	Aasa Dehydrogenase Deficiency
Antiquitin Deficiency	Pyridoxine Dependency
Glutamate Decarboxylase Deficiency	Pyridoxine-Dependent Seizures
Deficiency Of Glutamate Decarboxylase

Gyrate Atrophy Of Choroid And Retina

Gyrate Atrophy	Ornithine Aminotransferase Deficiency
HOGA	Hyperornithinemia With Gyrate Atrophy Of Choroid And Retina
Oat Deficiency	Okt Deficiency
Hyperornithinemia	Ornithine Keto Acid Aminotransferase Deficiency
Ornithine-Delta-Aminotransferase Deficiency	Gyrate Atrophy Of The Choroid And Retina
GACR	Gyrate Atrophy Of Choroid And Retina With Or Without Ornithinemia
Gyrate Atrophy Of The Retina	Ornithinemia With Gyrate Atrophy
Ornithinemia	Fuchs Atrophia Gyrata Chorioideae Et Retinae
Hyperornithinemia-Gyrate Atrophy Of Choroid And Retina Syndrome	Gyrate Atrophy Of The Choroid And/Or Retina
Girate Atrophy Of The Retina	Ornithine Ketoacid Aminotransferase Deficiency
Atrophy, Gyrate, Of Choroid And Retina

Spastic Paraplegia 10, Autosomal Dominant

SPG10	Hereditary Spastic Paraplegia 10
Autosomal Dominant Spastic Paraplegia Type 10	Spastic Paraplegia 10
Spastic Paraplegia 10 With Or Without Peripheral Neuropathy	Autosomal Dominant Spastic Paraplegia 10
Autosomal Dominant Spastic Paraplegia	Spastic Paraplegia, Autosomal Dominant
Paraplegia, Spastic, Autosomal Dominant, Type 10

Related Agents

Pre-clinical Phase

Bioactive Molecules (2)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-156443	YG1702	Inhibitor	99.21%	Unkown
HY-RS00559	ALDH18A1 Human Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Macaca mulatta	ALDH18A1	VGNC	VGNC:69821
Mus musculus	ALDH18A1	MGD	MGI:1888908
Canis familiaris	ALDH18A1	VGNC	VGNC:37781
Bos taurus	ALDH18A1	VGNC	VGNC:25807
Felis catus	ALDH18A1	VGNC	VGNC:69191
Rattus norvegicus	ALDH18A1	RGD	RGD:1311431