Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs Transcription factors Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	212
Gene name	5'-aminolevulinate synthase 2
Gene symbol	ALAS2
Synonyms (NCBI Gene)	ALAS-EALASEANH1ASBSIDBA1XLDPPXLEPPXLSA
Chromosome	X
Chromosome location	Xp11.21
Summary	The product of this gene specifies an erythroid-specific mitochondrially located enzyme. The encoded protein catalyzes the first step in the heme biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive sideroblastic anemia. Alterna

Show/Hide all (21)

SNP ID	Visualize variation	Clinical significance	Consequence
rs28935484	T>A	Pathogenic	Coding sequence variant, missense variant
rs137852299	A>T	Pathogenic	Coding sequence variant, missense variant
rs137852300	G>C	Pathogenic	Coding sequence variant, missense variant
rs137852301	G>T	Pathogenic	Coding sequence variant, missense variant
rs137852302	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852303	T>G	Pathogenic	Coding sequence variant, missense variant
rs137852304	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852305	G>A	Pathogenic	Coding sequence variant, missense variant
rs137852307	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852308	C>A,T	Pathogenic	Coding sequence variant, missense variant
rs137852309	G>C	Pathogenic	Coding sequence variant, missense variant
rs137852310	A>G	Pathogenic	Coding sequence variant, missense variant
rs137852311	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs150055592	G>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign, benign-likely-benign	Synonymous variant, coding sequence variant
rs201062903	G>A	Conflicting-interpretations-of-pathogenicity, benign, likely-benign	Missense variant, coding sequence variant
rs863223901	C>T	Pathogenic	Missense variant, coding sequence variant
rs863223902	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs863223903	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs863223904	C>T	Pathogenic	Missense variant, coding sequence variant
rs1057522832	C>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1557248142	G>T	Pathogenic	Missense variant, coding sequence variant

Show/Hide all (2)

Transcription factor	Regulation	Reference
GATA1	Unknown	23935018
HIF1A	Activation	21207956

Show/Hide all (37)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001666	Process	Response to hypoxia	IDA	16234850
GO:0003870	Function	5-aminolevulinate synthase activity	IBA
GO:0003870	Function	5-aminolevulinate synthase activity	IDA	14643893, 32499479
GO:0003870	Function	5-aminolevulinate synthase activity	IEA
GO:0003870	Function	5-aminolevulinate synthase activity	IMP	21252495, 21309041, 21653323
GO:0005515	Function	Protein binding	IPI	10727444, 14643893, 16234850, 25416956, 25910212, 32296183
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	10727444, 14643893
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IDA	14643893
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006778	Process	Porphyrin-containing compound metabolic process	IEA
GO:0006782	Process	Protoporphyrinogen IX biosynthetic process	IDA	32499479
GO:0006782	Process	Protoporphyrinogen IX biosynthetic process	IEA
GO:0006783	Process	Heme biosynthetic process	IBA
GO:0006783	Process	Heme biosynthetic process	IEA
GO:0006783	Process	Heme biosynthetic process	ISS
GO:0006783	Process	Heme biosynthetic process	NAS	14643893
GO:0006785	Process	Heme B biosynthetic process	IDA	2050125
GO:0006879	Process	Intracellular iron ion homeostasis	IEA
GO:0006879	Process	Intracellular iron ion homeostasis	ISS
GO:0016020	Component	Membrane	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016746	Function	Acyltransferase activity	IEA
GO:0030170	Function	Pyridoxal phosphate binding	IEA
GO:0030218	Process	Erythrocyte differentiation	IEA
GO:0030218	Process	Erythrocyte differentiation	ISS
GO:0030218	Process	Erythrocyte differentiation	NAS	2050125
GO:0032364	Process	Intracellular oxygen homeostasis	NAS	16234850
GO:0033014	Process	Tetrapyrrole biosynthetic process	IEA
GO:0042541	Process	Hemoglobin biosynthetic process	IBA
GO:0042541	Process	Hemoglobin biosynthetic process	IEA
GO:0042541	Process	Hemoglobin biosynthetic process	ISS
GO:0048821	Process	Erythrocyte development	IBA

MIM	HGNC	e!Ensembl
301300	397	ENSG00000158578

P22557

Protein name

5-aminolevulinate synthase, erythroid-specific, mitochondrial (ALAS-E) (EC 2.3.1.37) (5-aminolevulinic acid synthase 2) (Delta-ALA synthase 2) (Delta-aminolevulinate synthase 2)

Protein function

Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products (PubMed:14643893, PubMed:21252495, PubMed:21309041, PubMed:21653323, PubMed:32499479

PDB

5QQQ , 5QQR , 5QQS , 5QQT , 5QQU , 5QQV , 5QQW , 5QQX , 5QQY , 5QQZ , 5QR0 , 5QR1 , 5QR2 , 5QR3 , 5QR4 , 5QR5 , 5QR6 , 5QR7 , 5QR8 , 5QR9 , 5QRA , 5QRB , 5QRC , 5QRD , 5QRE , 5QT3 , 6HRH

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF09029	Preseq_ALAS	52 → 100	5-aminolevulinate synthase presequence	Domain
PF00155	Aminotran_1_2	189 → 536	Aminotransferase class I and II	Domain

Tissue specificity

TISSUE SPECIFICITY: [Isoform 1]: Erythroid-specific. {ECO:0000269|PubMed:14643893, ECO:0000269|PubMed:2050125}.; TISSUE SPECIFICITY: [Isoform 2]: Erythroid-specific. {ECO:0000269|PubMed:14643893}.; TISSUE SPECIFICITY: [Isoform 3]: Erythroid-specific. {ECO

Sequence

MVTAAMLLQCCPVLARGPTSLLGKVVKTHQFLFGIGRCPILATQGPNCSQIHLKATKAGG
DSPSWAKGHCPFMLSELQDGKSKIVQKAAPEVQEDVKAFKTDLPSSLVSVSLRKPFSGPQ
EQEQISGKVTHLIQNNMPGNYVFSYDQFFRDKIMEKKQDHTYRVFKTVNRWADAYPFAQH
FSEASVASKDVSVWCSNDYLGMSRHPQVLQATQETLQRHGAGAGGTRNISGTSKFHVELE
QELAELHQKDSALLFSSCFVANDSTLFTLAKILPGCEIYSDAGNHASMIQGIRNSGAAKF
VFRHNDPDHLKKLLEKSNPKIPKIVAFETVHSMDGAICPLEELCDVSHQYGALTFVDEVH
AVGLYGSRGAGIGERDGIMHKIDIISGTLGKAFGCVGGYIASTRDLVDMVRSYAAGFIFT
TSLPPMVLSGALESVRLLKGEEGQALRRAHQRNVKHMRQLLMDRGLPVIPCPSHIIPIRV
GNAALNSKLCDLLLSKHGIYVQAINYPTVPRGEELLRLAPSPHHSPQMMEDFVEKLLLAW
TAVGLPLQDVSVAACNFCRRPVHFELMSEWERSYFGNMGPQYVTTYA

Sequence length

587

Interactions

View interactions

	KEGG		Reactome
	Glycine, serine and threonine metabolism Porphyrin metabolism Metabolic pathways Biosynthesis of cofactors		Heme biosynthesis

114

Show/Hide Causal Diseases (6)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
ALAS2-related disorder	Pathogenic	rs137852311	RCV004730841
Pancreatic adenocarcinoma	Pathogenic	rs863223900	RCV005940001
See cases	Likely pathogenic; Pathogenic	rs387906472	RCV004584322
Sideroblastic anemia 1, late-onset	Pathogenic; Likely pathogenic	rs137852303, rs137852304	RCV000011218 RCV000011219
X-linked erythropoietic protoporphyria	Likely pathogenic; Pathogenic	rs387906472, rs387906473, rs397514730, rs879255567	RCV000011228 RCV000011229 RCV000054488 RCV000054489
X-linked sideroblastic anemia 1	Likely pathogenic; Pathogenic	rs2146722839, rs2519597816, rs137852299, rs137852300, rs137852301, rs137852302, rs137852304, rs28935484, rs137852305, rs137852306, rs137852307, rs137852308, rs137852309, rs137852310, rs137852311 View all (5 more)	RCV001376189 RCV003226058 RCV000011214 RCV000011215 RCV000011216 RCV000011217 RCV001729346 RCV003322588 RCV000011221 RCV000011222 RCV000011223 RCV000011224 RCV000011225 RCV000011227 RCV000011230 RCV000011231 RCV004017207 RCV005402349 RCV000626482 RCV001352676 RCV001534614

Show/Hide Unknown Diseases (5)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Acute myeloid leukemia	Benign	rs45468097	RCV005890565
Cervical cancer	Benign	rs45468097	RCV005890566
Developmental and epileptic encephalopathy, 36	Conflicting classifications of pathogenicity	rs139596860	RCV004698465
Sideroblastic Anemia and Ataxia	Uncertain significance	rs754383602	RCV000288714
Thymoma	Benign	rs45468097	RCV005890567

Show/Hide Text Mining Associations (44)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Actin Accumulation Myopathy	Associate	23348515
Anemia	Associate	7949148
Anemia Diamond Blackfan	Associate	23348515
Anemia Hemolytic	Associate	31338833
Anemia Hemolytic Congenital	Associate	37697358
Anemia hypochromic microcytic	Associate	38360212
Anemia Macrocytic	Associate	25705881
Anemia Refractory	Stimulate	16527891
Anemia Refractory	Associate	19692701, 7560104
Anemia Sickle Cell	Associate	17508724
Anemia Sideroblastic	Associate	10577279, 12531813, 1577484, 19731322, 22983749, 23935018, 25985931, 29908199, 33858445, 35637209, 36028755, 38360212
Ataxia	Associate	1577484
beta Thalassemia	Associate	11110715, 21750082
Cardiomyopathy Dilated	Associate	36769209
Cockayne Syndrome	Associate	19731322
Cognition Disorders	Associate	40229714
Familial Primary Pulmonary Hypertension	Associate	34876579
Heart Failure	Stimulate	23500306
Hemochromatosis	Associate	10029606
Hepatitis C	Associate	18823803
Hepatitis C Chronic	Associate	18823803
Hypoxia	Stimulate	19187226
Hypoxia	Associate	23500306
Immunologic Deficiency Syndromes	Inhibit	29908199
Inflammatory Bowel Diseases	Associate	31618209
Iron Overload	Associate	10029606, 18760763, 18823803
Leukemia Myeloid	Associate	9133617
Liver Diseases	Associate	18760763, 23348515
Neoplastic Syndromes Hereditary	Associate	9488633
Neurodegenerative Diseases	Associate	40229714
Photosensitivity Disorders	Associate	23348515
Porphyria Acute Intermittent	Associate	23650938
Porphyria Erythropoietic	Associate	21653323
Porphyrias	Associate	18760763, 30391163, 32499479
Primary Myelofibrosis	Associate	34238135
Protoporphyria Erythropoietic	Associate	23364466, 30391163, 31076252, 36898083
Protoporphyria Erythropoietic X Linked Dominant	Associate	18760763, 21653323
Pulmonary Arterial Hypertension	Associate	20808962
Pulmonary Disease Chronic Obstructive	Associate	25407108
Purpura Thrombocytopenic Idiopathic	Associate	38053370
Ring Chromosomes	Associate	29908199, 7560104
Sleep Deprivation	Associate	40229714
Sleep Wake Disorders	Associate	40229714
X linked sideroblastic anemia	Associate	10029606, 10444183, 11110715, 12393718, 12531813, 12663458, 1577484, 18760763, 21653323, 22269113, 22740690, 22983749, 24166784, 24829177, 29908199 View all (8 more)

ALAS2 (5'-aminolevulinate synthase 2)