| Tbio | Delta-1-pyrroline-5-carboxylate synthase |
Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine.
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]
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]
Comments
| Disease | Target Count |
|---|---|
| Cutis Laxa, Autosomal Dominant | 3 |
| De Barsy syndrome | 1 |
| SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT (disorder) | 1 |
| Disease | Target Count | P-value |
|---|---|---|
| non-small cell lung cancer | 2798 | 9.36027392824498E-23 |
| lung adenocarcinoma | 2714 | 2.9268472998932E-11 |
| ulcerative colitis | 2087 | 9.51105688671461E-10 |
| ependymoma | 2514 | 7.76952386861222E-9 |
| atypical teratoid/rhabdoid tumor | 1095 | 1.86679967578511E-8 |
| medulloblastoma, large-cell | 6234 | 1.13336068951411E-6 |
| pediatric high grade glioma | 2712 | 4.01382984218317E-6 |
| pilocytic astrocytoma | 3086 | 5.05945102805999E-6 |
| ovarian cancer | 8492 | 2.52560839420524E-5 |
| lung cancer | 4473 | 2.77726540918303E-5 |
| osteosarcoma | 7933 | 6.462239640132E-5 |
| group 3 medulloblastoma | 2254 | 3.61871539626368E-4 |
| invasive ductal carcinoma | 2950 | 0.00106402793477332 |
| psoriasis | 6685 | 0.0025006011692103 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Intellectual disability | 573 | 0.0 | 4.0 |
| Neurodegenerative disease | 383 | 0.0 | 4.0 |
| hereditary spastic paraplegia | 313 | 0.0 | 4.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Cutis laxa | 28 | 5.738 | 2.9 |
| Pathological gambling | 16 | 4.102 | 2.1 |
| Warburg micro syndrome | 19 | 3.318 | 1.7 |
| Gyrate atrophy | 8 | 3.106 | 1.6 |
| Disease | log2 FC | p |
|---|---|---|
| psoriasis | 1.200 | 0.003 |
| osteosarcoma | 2.336 | 0.000 |
| ependymoma | 1.100 | 0.000 |
| group 3 medulloblastoma | 1.500 | 0.000 |
| atypical teratoid/rhabdoid tumor | 1.500 | 0.000 |
| medulloblastoma, large-cell | 2.000 | 0.000 |
| non-small cell lung cancer | 1.543 | 0.000 |
| lung cancer | 2.200 | 0.000 |
| pediatric high grade glioma | 1.100 | 0.000 |
| pilocytic astrocytoma | 1.100 | 0.000 |
| lung adenocarcinoma | 1.300 | 0.000 |
| invasive ductal carcinoma | 1.200 | 0.001 |
| ulcerative colitis | -1.300 | 0.000 |
| ovarian cancer | 2.800 | 0.000 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Horse | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Pig | OMA EggNOG Inparanoid |
| Opossum | EggNOG Inparanoid |
| Platypus | OMA EggNOG |
| Anole lizard | OMA EggNOG Inparanoid |
| Xenopus | OMA EggNOG Inparanoid |
| Zebrafish | OMA Inparanoid |
| C. elegans | OMA EggNOG Inparanoid |
| S.cerevisiae | EggNOG Inparanoid |
| PMID | Text |
|---|---|
| 26320891 | Recurrent De Novo Mutations Affecting Residue Arg138 of Pyrroline-5-Carboxylate Synthase Cause a Progeroid Form of Autosomal-Dominant Cutis Laxa. |
| 26026163 | autosomal recessive transmission of ALDH18A1 mutations, and predominant complex hereditary spastic paraplegia with marked cognitive impairment |
| 24913064 | A frameshift deletion of one nucleotide and a microdeletion affecting the ALDH18A1 gene, respectively, in a homozygous state in both patients, was identified. |
| 23125841 | Tandem affinity purification and mass spectrometry analysis identify aldehyde dehydrogenase 18 family member A1 (ALDH18A1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells |
| 21739576 | expansion of the phenotypic spectrum associated with mutations in ALDH18A1 |
| 20946940 | ALDH18A1 genetic variants are associated with Down syndrome in subjects with dementia of Alzheimer's disease. |
| 20946940 | Observational study of gene-disease association. (HuGE Navigator) |
| 20877624 | Observational study of gene-disease association. (HuGE Navigator) |
| 20819778 | Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) |
| 20379614 | Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) |
| More... |
MLSQVYRCGFQPFNQHLLPWVKCTTVFRSHCIQPSVIRHVRSWSNIPFITVPLSRTHGKSFAHRSELKHA 1 - 70 KRIVVKLGSAVVTRGDECGLALGRLASIVEQVSVLQNQGREMMLVTSGAVAFGKQRLRHEILLSQSVRQA 71 - 140 LHSGQNQLKEMAIPVLEARACAAAGQSGLMALYEAMFTQYSICAAQILVTNLDFHDEQKRRNLNGTLHEL 141 - 210 LRMNIVPIVNTNDAVVPPAEPNSDLQGVNVISVKDNDSLAARLAVEMKTDLLIVLSDVEGLFDSPPGSDD 211 - 280 AKLIDIFYPGDQQSVTFGTKSRVGMGGMEAKVKAALWALQGGTSVVIANGTHPKVSGHVITDIVEGKKVG 281 - 350 TFFSEVKPAGPTVEQQGEMARSGGRMLATLEPEQRAEIIHHLADLLTDQRDEILLANKKDLEEAEGRLAA 351 - 420 PLLKRLSLSTSKLNSLAIGLRQIAASSQDSVGRVLRRTRIAKNLELEQVTVPIGVLLVIFESRPDCLPQV 421 - 490 AALAIASGNGLLLKGGKEAAHSNRILHLLTQEALSIHGVKEAVQLVNTREEVEDLCRLDKMIDLIIPRGS 491 - 560 SQLVRDIQKAAKGIPVMGHSEGICHMYVDSEASVDKVTRLVRDSKCEYPAACNALETLLIHRDLLRTPLF 561 - 630 DQIIDMLRVEQVKIHAGPKFASYLTFSPSEVKSLRTEYGDLELCIEVVDNVQDAIDHIHKYGSSHTDVIV 631 - 700 TEDENTAEFFLQHVDSACVFWNASTRFSDGYRFGLGAEVGISTSRIHARGPVGLEGLLTTKWLLRGKDHV 701 - 770 VSDFSEHGSLKYLHENLPIPQRNTN 771 - 795 //
| PMID | Year | Title |
|---|---|---|
| 26320891 | 2015 | Recurrent De Novo Mutations Affecting Residue Arg138 of Pyrroline-5-Carboxylate Synthase Cause a Progeroid Form of Autosomal-Dominant Cutis Laxa. |
| 26297558 | 2016 | ALDH18A1 gene mutations cause dominant spastic paraplegia SPG9: loss of function effect and plausibility of a dominant negative mechanism. |
| 26026163 | 2015 | Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. |
| 25944712 | 2015 | N-terminome analysis of the human mitochondrial proteome. |
| 25416956 | 2014 | A proteome-scale map of the human interactome network. |
| 24913064 | 2014 | Severe congenital cutis laxa with cardiovascular manifestations due to homozygous deletions in ALDH18A1. |
| 24816252 | 2014 | An atlas of genetic influences on human blood metabolites. |
| 24767728 | 2014 | Cutis laxa, fat pads and retinopathy due to ALDH18A1 mutation and review of the literature. |
| 24275569 | 2014 | An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. |
| 22658674 | 2012 | Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. |
| More... |
