ALAS1 (5'-aminolevulinate synthase 1)

Gene

• Entrez ID: 211
• Gene name: 5'-aminolevulinate synthase 1
• Gene symbol: ALAS1
• Synonyms (NCBI Gene): ALAS, ALAS-H, ALAS3, ALASH, MIG4
• Chromosome: 3
• Chromosome location: 3p21.2
• Summary: This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis. The enzyme encoded by this gene is the housekeeping enzyme; a separate gene encodes a form of the enzyme that is specific for

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT042490	hsa-miR-423-3p	CLASH	23622248
MIRT042198	hsa-miR-484	CLASH	23622248
MIRT776862	hsa-miR-410	CLIP-seq
MIRT776863	hsa-miR-4282	CLIP-seq
MIRT776864	hsa-miR-889	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
NFIC	Unknown	15123725

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001666	Process	Response to hypoxia	IEA
GO:0003870	Function	5-aminolevulinate synthase activity	IBA
GO:0003870	Function	5-aminolevulinate synthase activity	IDA	16234850, 17975826
GO:0003870	Function	5-aminolevulinate synthase activity	IEA
GO:0005515	Function	Protein binding	IPI	21516116, 25416956, 25910212, 28514442, 31515488, 32296183, 32814053, 33961781
GO:0005654	Component	Nucleoplasm	IDA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IDA
GO:0006778	Process	Porphyrin-containing compound metabolic process	IEA
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	TAS	2347585
GO:0006784	Process	Heme A biosynthetic process	IEA
GO:0006785	Process	Heme B biosynthetic process	IEA
GO:0009410	Process	Response to xenobiotic stimulus	IEA
GO:0009635	Process	Response to herbicide	IEA
GO:0010045	Process	Response to nickel cation	IEA
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:0031667	Process	Response to nutrient levels	IEA
GO:0032025	Process	Response to cobalt ion	IEA
GO:0032869	Process	Cellular response to insulin stimulus	IEA
GO:0033014	Process	Tetrapyrrole biosynthetic process	IEA
GO:0034698	Process	Response to gonadotropin	IEA
GO:0042541	Process	Hemoglobin biosynthetic process	IBA
GO:0042802	Function	Identical protein binding	IPI	25416956, 32296183
GO:0045471	Process	Response to ethanol	IEA
GO:0048034	Process	Heme O biosynthetic process	IEA
GO:0048821	Process	Erythrocyte development	IBA
GO:0051591	Process	Response to cAMP	IEA
GO:0070541	Process	Response to platinum ion	IEA
GO:1903412	Process	Response to bile acid	IDA	17975826

Other IDs

• MIM: 125290
• HGNC: 396
• e!Ensembl: ENSG00000023330

Protein

• UniProt ID: P13196
• Protein name: 5-aminolevulinate synthase, non-specific, mitochondrial (ALAS-H) (EC 2.3.1.37) (5-aminolevulinic acid synthase 1) (Delta-ALA synthase 1) (Delta-aminolevulinate synthase 1)
• 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.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF09029	Preseq_ALAS	2 → 138	5-aminolevulinate synthase presequence	Domain
  PF00155	Aminotran_1_2	243 → 590	Aminotransferase class I and II	Domain

• Sequence:

  MESVVRRCPFLSRVPQAFLQKAGKSLLFYAQNCPKMMEVGAKPAPRALSTAAVHYQQIKE
  TPPASEKDKTAKAKVQQTPDGSQQSPDGTQLPSGHPLPATSQGTASKCPFLAAQMNQRGS
  SVFCKASLELQEDVQEMNAVRKEVAETSAGPSVVSVKTDGGDPSGLLKNFQDIMQKQRPE
  RVSHLLQDNLPKSVSTFQYDRFFEKKIDEKKNDHTYRVFKTVNRRAHIFPMADDYSDSLI
  TKKQVSVWCSNDYLGMSRHPRVCGAVMDTLKQHGAGAGGTRNISGTSKFHVDLERELADL
  HGKDAALLFSSCFVANDSTLFTLAKMMPGCEIYSDSGNHASMIQGIRNSRVPKYIFRHND
  VSHLRELLQRSDPSVPKIVAFETVHSMDGAVCPLEELCDVAHEFGAITFVDEVHAVGLYG
  ARGGGIGDRDGVMPKMDIISGTLGKAFGCVGGYIASTSSLIDTVRSYAAGFIFTTSLPPM
  LLAGALESVRILKSAEGRVLRRQHQRNVKLMRQMLMDAGLPVVHCPSHIIPVRVADAAKN
  TEVCDELMSRHNIYVQAINYPTVPRGEELLRIAPTPHHTPQMMNYFLENLLVTWKQVGLE
  LKPHSSAECNFCRRPLHFEVMSEREKSYFSGLSKLVSAQA

• Sequence length: 640

Pathways

KEGG:

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

Reactome:

Heme biosynthesis
PPARA activates gene expression
Transcriptional activation of mitochondrial biogenesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CROHN'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISORDERS OF PORPHYRIN METABOLISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PORPHYRIAS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute intermittent porphyria	Intermittent Porphyria	BEFREE	17298222, 21659532, 23650938, 29498764, 30726693, 30777612, 31154864, 31792921		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	27561203		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	19477221	Inhibit	★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	BEFREE	31754094		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar disorder	Pubtator	31754094	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	32270771	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	22070747		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	22070747		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	31754094		★☆☆☆☆ Found in Text Mining only
Disorders of Porphyrin Metabolism	Porphyria	BEFREE	27838491, 30737140		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Disorders of Porphyrin Metabolism	Porphyria	CTD_human_DG	9222176		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	37509133	Associate	★☆☆☆☆ Found in Text Mining only
Erythropoietic Protoporphyria	Erythropoietic Protoporphyria	BEFREE	19744342, 30737140		★☆☆☆☆ Found in Text Mining only
Hereditary Coproporphyria	Hereditary Coproporphyria	BEFREE	31154864		★☆☆☆☆ Found in Text Mining only
Laryngeal Neoplasms	Laryngeal neoplasm	Pubtator	31173291	Associate	★☆☆☆☆ Found in Text Mining only
Liver Failure, Acute	Liver failure	BEFREE	15547665		★☆☆☆☆ Found in Text Mining only
Liver Failure, Acute	Liver failure	LHGDN	15547665		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	16211407		★☆☆☆☆ Found in Text Mining only
MELORHEOSTOSIS, ISOLATED	Melorheostosis	BEFREE	8843957		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	19650912		★☆☆☆☆ Found in Text Mining only
Porphyria Acute Intermittent	Porphyria	Pubtator	23650938, 26062020, 4270345	Associate	★☆☆☆☆ Found in Text Mining only
Porphyria, Erythropoietic	Congenital erythropoietic porphyria	BEFREE	28118224		★☆☆☆☆ Found in Text Mining only
Porphyrias	Porphyria	Pubtator	21659532	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate carcinoma	Prostate cancer	BEFREE	16211407		★☆☆☆☆ Found in Text Mining only
Protoporphyria Erythropoietic	Erythropoietic protoporphyria	Pubtator	28874591, 30391163	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	30948194		★☆☆☆☆ Found in Text Mining only
Sideroblastic anemia	Sideroblastic Anemia	LHGDN	11929048		★☆☆☆☆ Found in Text Mining only
Sideroblastic anemia	Sideroblastic Anemia	BEFREE	30737140		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	19650912	Associate	★☆☆☆☆ Found in Text Mining only
Variegate Porphyria	Variegate Porphyria	BEFREE	31154864		★☆☆☆☆ Found in Text Mining only