ALAS2 (5'-aminolevulinate synthase 2)

Gene

• Entrez ID: 212
• Gene name: 5'-aminolevulinate synthase 2
• Gene symbol: ALAS2
• Synonyms: ALAS-E, ALASE, ANH1, ASB, SIDBA1, XLDPP, XLEPP, XLSA
• 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

SNPs

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

Transcription factors

Transcription factor	Regulation	Reference
GATA1	Unknown	23935018
HIF1A	Activation	21207956

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001666	Process	Response to hypoxia	IBA	21873635
GO:0001666	Process	Response to hypoxia	IDA	16234850
GO:0003870	Function	5-aminolevulinate synthase activity	IBA	21873635
GO:0003870	Function	5-aminolevulinate synthase activity	IDA	14643893
GO:0005515	Function	Protein binding	IPI	10727444, 14643893, 16234850, 25416956
GO:0005739	Component	Mitochondrion	IBA	21873635
GO:0005739	Component	Mitochondrion	IDA	10727444, 14643893
GO:0005743	Component	Mitochondrial inner membrane	IDA	14643893
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006782	Process	Protoporphyrinogen IX biosynthetic process	IEA
GO:0006783	Process	Heme biosynthetic process	IBA	21873635
GO:0006783	Process	Heme biosynthetic process	ISS
GO:0006783	Process	Heme biosynthetic process	NAS	14643893
GO:0006783	Process	Heme biosynthetic process	TAS
GO:0006879	Process	Cellular iron ion homeostasis	ISS
GO:0030170	Function	Pyridoxal phosphate binding	IEA
GO:0030218	Process	Erythrocyte differentiation	ISS
GO:0030218	Process	Erythrocyte differentiation	NAS	2050125
GO:0032364	Process	Oxygen homeostasis	NAS	16234850
GO:0042541	Process	Hemoglobin biosynthetic process	IBA	21873635
GO:0042541	Process	Hemoglobin biosynthetic process	ISS
GO:0048821	Process	Erythrocyte development	IBA	21873635

Other IDs

• MIM: 301300
• HGNC: 397
• e!Ensembl: ENSG00000158578

Protein

• UniProt ID: 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

• Sequence:

  MVTAAMLLQCCPVLARGPTSLLGKVVKTHQFLFGIGRCPILATQGPNCSQIHLKATKAGG
  DSPSWAKGHCPFMLSELQDGKSKIVQKAAPEVQEDVKAFKTDLPSSLVSVSLRKPFSGPQ
  EQEQISGKVTHLIQNNMPGNYVFSYDQFFRDKIMEKKQDHTYRVFKTVNRWADAYPFAQH
  FSEASVASKDVSVWCSNDYLGMSRHPQVLQATQETLQRHGAGAGGTRNISGTSKFHVELE
  QELAELHQKDSALLFSSCFVANDSTLFTLAKILPGCEIYSDAGNHASMIQGIRNSGAAKF
  VFRHNDPDHLKKLLEKSNPKIPKIVAFETVHSMDGAICPLEELCDVSHQYGALTFVDEVH
  AVGLYGSRGAGIGERDGIMHKIDIISGTLGKAFGCVGGYIASTRDLVDMVRSYAAGFIFT
  TSLPPMVLSGALESVRLLKGEEGQALRRAHQRNVKHMRQLLMDRGLPVIPCPSHIIPIRV
  GNAALNSKLCDLLLSKHGIYVQAINYPTVPRGEELLRLAPSPHHSPQMMEDFVEKLLLAW
  TAVGLPLQDVSVAACNFCRRPVHFELMSEWERSYFGNMGPQYVTTYA

• Sequence length: 587

Pathways

KEGG:

Glycine, serine and threonine metabolism
Porphyrin metabolism
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Heme biosynthesis

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia, Anemia, Macrocytic, Microcytic hypochromic anemia (disorder)	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Erythropoietic protoporphyria, x-linked	X-linked erythropoietic protoporphyria	rs387906472, rs387906473, rs397514730, rs879255567
Protoporphyria, erythropoietic	Protoporphyria, Erythropoietic, X-Linked Dominant	rs118204039, rs786205245, rs202147607, rs118204040, rs149067146, rs786205246, rs879255507, rs764466739, rs786205247, rs786205248, rs397514476, rs370708663, rs150146721, rs1555412542, rs765518889, rs146269992, rs1598996309, rs1599003455	29903433, 23263862, 10029606
Sideroblastic anemia	Sideroblastic anemia	rs763817505	16892088, 16716198
Sideroblastic anemia, x-linked	X-linked sideroblastic anemia	rs137852299, rs137852300, rs137852301, rs137852302, rs137852304, rs28935484, rs137852305, rs137852306, rs137852307, rs137852308, rs137852309, rs137852310, rs137852311, rs1557248142	9858242, 10577279, 29903433, 21252495, 12393718, 10029606, 1570328, 23263862, 12031592, 18637800, 21309041, 8107717, 19731322