Property Summary

NCBI Gene PubMed Count 49
PubMed Score 144.40
PubTator Score 142.26

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (8)

Disease log2 FC p
osteosarcoma -6.999 1.2e-05
group 3 medulloblastoma -1.300 4.4e-03
tuberculosis 2.300 2.0e-02
breast carcinoma -1.500 2.3e-02
lung adenocarcinoma -1.300 1.6e-08
mucosa-associated lymphoid tissue lympho... 4.253 9.2e-03
ovarian cancer -1.700 5.1e-05
dermatomyositis 1.200 4.2e-02

Gene RIF (30)

PMID Text
26300302 data indicate that the X-linked protoporphyria variants possess enhanced ALAS activity and ALA dissociation rates, as well as distinct structural properties from those of wild-type hALAS
25705881 The ALAS2 Y365C mutation impairs pyridoxal 5'-phosphate binding to ALAS2, destabilizing the enzyme. X inactivation was not highly skewed in WBC from affected women. This X-linked dominant mutation perturbs erythropoiesis via cell-nonautonomous effects.
25179834 the primary deficiency in ferrochelatase leads to a secondary increase in ALAS2 expression.
24829177 In this article we add a novel mutation to the previously described 61 different ALAS2 mutations identified in X-linked sideroblastic anaemia patients.
24166784 5 families with X-linked sideroblastic anemia had mutations in a GATA transcription factor binding site located in a transcriptional enhancer element in intron 1 of the ALAS2 gene.
23935018 the 130-base pair enhancer region located in the first intron of the ALAS2 gene should be examined in patients with congenital sideroblastic anemia in whom the gene responsible is unknown.
23364466 Loss-of-function FECH and gain-of-function erythroid-specific ALAS2 mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria.
23348515 ALAS2 gain-of-function mutations increas the specific activity (DeltaAT, DeltaAGTG and p.Q548X) or stability (DeltaG) of the enzyme, thereby leading to the increased erythroid protoporphyrin accumulation causing X-linked protoporphyria.
23263862 A large gain-of-function domain within the C-terminus of ALAS2 is associated with X-linked dominant protoporphyria.
23223129 Late-onset photosensitivity was caused by ALAS2 mutation in a family with dominant protoporphyria.
22740690 X-linked sideroblastic anemia due to carboxyl-terminal ALAS2 mutations that cause loss of binding to the beta-subunit of succinyl-CoA synthetase (SUCLA2).
22269113 the C-terminal region of ALAS2 protein may function as an intrinsic modifier that suppresses catalytic activity and increases the degradation of its protein, each function of which is enhanced by the Met567Ile mutation and Val562Ala mutation, respectively
21800356 identification of five probands with sideroblastic anemia and ALAS2 R452S (due to SNP); all were African-American males; all presented with moderate anemia; the four adults presented with iron overload [a multi-case report from the United States]
21653323 Data suggest that ALAS2 gene mutations should be considered not only as causative of X-linked sideroblastic anemia (XLSA) and XLDPP but may also modulate gene function in other erythropoietic disorders.
21309041 Thirteen different ALAS2 mutations were identified in 16 out of 29 probands with sideroblastic anemia.
21252495 We found the previously published R452H and R452C ALAS2 mutations in 3 patients with X-linked sideroblastic anemia
21207956 HIF1-mediated ALAS2 upregulation promotes erythropoiesis to satisfy the needs of an organism under hypoxic conditions.
20850938 About 4% of unrelated EPP patients have X-linked dominant protoporphyria (MIM 300752) caused by gain-of-function mutations in the ALAS2 gene leading to an increased erythroid heme biosynthesis & protoporphyrin accumulation. Review.
19731322 Seven ALAS2 mutations were detected in eight sporadic CSA cases, two being novel: V301A in a male patient and R517G in a female patient
19187226 Hypoxia induces erythroid-specific 5-aminolevulinate synthase expression in human erythroid cells through transforming growth factor-beta signaling.
19066423 Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G.
18760763 gain-of-function mutations in ALAS2 cause a previously unrecognized form of porphyria, X-linked dominant protoporphyria, characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes
18569569 An impact of ALAD2 on blood lead levels or hemoglobin was not seen in Romanian women from a lead-contaminated region.
18555711 upon the NaBu stimulation, binding of Sp1 protein to ALAS2 promoter increased significantly, with concurrent increases in acetylation level of histone H3 and dimethylation level of H3-Lysine4 at ALAS2 promoter
16446107 ALAS2 mutations might contribute to more severe iron loading in persons with primary hemochromatosis.
16121195 sequence identity of ALAS from Rhodobacter capsulatus and human eALAS is 49%
15166166 there is nucleotide variation at Msn and Alas2 on the X chromosome
14643893 the major splice isoform of ALAS2 is functional in vivo and could significantly contribute to erythroid heme biosynthesis and hemoglobin formation
12663458 A C to G transversion at nucleotide -206 from the transcription start site was found in the proximal promoter region of ALAS2 in X-linked sideroblastic anemia. The region of the mutation may bind a novel and important erythroid regulatory element.
12031592 A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia.

AA Sequence

MVTAAMLLQCCPVLARGPTSLLGKVVKTHQFLFGIGRCPILATQGPNCSQIHLKATKAGGDSPSWAKGHC      1 - 70
PFMLSELQDGKSKIVQKAAPEVQEDVKAFKTDLPSSLVSVSLRKPFSGPQEQEQISGKVTHLIQNNMPGN     71 - 140
YVFSYDQFFRDKIMEKKQDHTYRVFKTVNRWADAYPFAQHFSEASVASKDVSVWCSNDYLGMSRHPQVLQ    141 - 210
ATQETLQRHGAGAGGTRNISGTSKFHVELEQELAELHQKDSALLFSSCFVANDSTLFTLAKILPGCEIYS    211 - 280
DAGNHASMIQGIRNSGAAKFVFRHNDPDHLKKLLEKSNPKIPKIVAFETVHSMDGAICPLEELCDVSHQY    281 - 350
GALTFVDEVHAVGLYGSRGAGIGERDGIMHKIDIISGTLGKAFGCVGGYIASTRDLVDMVRSYAAGFIFT    351 - 420
TSLPPMVLSGALESVRLLKGEEGQALRRAHQRNVKHMRQLLMDRGLPVIPCPSHIIPIRVGNAALNSKLC    421 - 490
DLLLSKHGIYVQAINYPTVPRGEELLRLAPSPHHSPQMMEDFVEKLLLAWTAVGLPLQDVSVAACNFCRR    491 - 560
PVHFELMSEWERSYFGNMGPQYVTTYA                                               561 - 587
//

Text Mined References (51)

PMID Year Title
26300302 2015 Human Erythroid 5-Aminolevulinate Synthase Mutations Associated with X-Linked Protoporphyria Disrupt the Conformational Equilibrium and Enhance Product Release.
25705881 2015 X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation.
25416956 2014 A proteome-scale map of the human interactome network.
25179834 2015 In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability.
24829177 2014 X-linked sideroblastic anaemia due to ALAS? mutations in the Netherlands: a disease in disguise.
24166784 2014 X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations.
23935018 2014 Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia.
23364466 2013 Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria.
23348515 2013 Molecular expression and characterization of erythroid-specific 5-aminolevulinate synthase gain-of-function mutations causing X-linked protoporphyria.
23263862 2013 Molecular and functional analysis of the C-terminal region of human erythroid-specific 5-aminolevulinic synthase associated with X-linked dominant protoporphyria (XLDPP).
23223129 2013 Late-onset X-linked dominant protoporphyria: an etiology of photosensitivity in the elderly.
22740690 2012 X-linked sideroblastic anemia due to carboxyl-terminal ALAS2 mutations that cause loss of binding to the ?-subunit of succinyl-CoA synthetase (SUCLA2).
22269113 2012 The carboxyl-terminal region of erythroid-specific 5-aminolevulinate synthase acts as an intrinsic modifier for its catalytic activity and protein stability.
21800356 2011 Sideroblastic anemia, iron overload, and ALAS2 R452S in African-American males: phenotype and genotype features of five unrelated patients.
21653323 2011 ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria.
21309041 2011 Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations.
21252495 2011 New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine.
21207956 2011 Hypoxic induction of human erythroid-specific ?-aminolevulinate synthase mediated by hypoxia-inducible factor 1.
20850938 2010 [Inheritance in erythropoietic protoporphyria].
19731322 2010 Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations.
19187226 2009 Hypoxia induces erythroid-specific 5-aminolevulinate synthase expression in human erythroid cells through transforming growth factor-beta signaling.
19066423 2008 Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G.
18760763 2008 C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload.
18569569 2008 Lack of association of delta-aminolevulinate dehydratase polymorphisms with blood lead levels and hemoglobin in Romanian women from a lead-contaminated region.
18555711 Sodium butyrate activates erythroid-specific 5-aminolevulinate synthase gene through Sp1 elements at its promoter.
16446107 Three kinships with ALAS2 P520L (c. 1559 C --> T) mutation, two in association with severe iron overload, and one with sideroblastic anemia and severe iron overload.
16234850 2005 Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition.
16121195 2005 Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans.
15772651 2005 The DNA sequence of the human X chromosome.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15166166 2004 Nucleotide variation at Msn and Alas2, two genes flanking the centromere of the X chromosome in humans.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14643893 2004 The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis.
12663458 2003 A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12393718 2002 Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation.
12031592 2002 A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia.
10727444 2000 Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia.
10577279 1999 A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia.
10029606 1999 Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.
9858242 1998 R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity.
9642238 1998 Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8107717 1994 X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase.
2347585 1990 Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome.
2263504 1990 Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes.
2050125 1991 Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA.
1939222 1991 Biosynthesis of delta-aminolevulinic acid and the regulation of heme formation by immature erythroid cells in man.
1577484 1992 Assignment of human erythroid delta-aminolevulinate synthase (ALAS2) to a distal subregion of band Xp11.21 by PCR analysis of somatic cell hybrids containing X; autosome translocations.
1570328 1992 Enzymatic defect in "X-linked" sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency.