ALAS1 Gene

Name	5'-aminolevulinate synthase 1
Description	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 erythroid tissue. The level of the mature encoded protein is regulated by heme: high levels of heme down-regulate the mature enzyme in mitochondria while low heme levels up-regulate. A pseudogene of this gene is located on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n 5‐Aminolevulinate synthase 1 (ALAS1) is the first and rate‐limiting enzyme in the mitochondrial heme biosynthetic pathway, whose expression and degradation are tightly regulated to maintain cellular heme homeostasis. In liver and extrahepatic tissues, ALAS1 is transcriptionally induced by nuclear receptors and their coactivators – for example, ALAS1 is upregulated by PPARα in human hepatocytes (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ",\n and its expression in muscle is reduced in the absence of PGC‑1α, indicating a key role for these factors in coupling metabolic demand to heme synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, the induction of ALAS1 by PGC‑1β further supports its role as a target gene co‐regulated by transcription factors such as NRF‑1 and ERRα."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the liver, ALAS1 not only contributes to heme production for cytochrome P450 enzymes but also links metabolic state to hormonal regulation, as illustrated by its necessity for PGC‑1α–mediated suppression of FGF21 via Rev‑Erbα."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, during adipogenesis, an increase in ALAS1 expression is critical for the enhanced heme synthesis that facilitates REV‑ERB activation and promotes adipocyte differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n ALAS1 protein levels are further controlled post‐translationally by a conserved heme-dependent negative feedback mechanism. Binding of heme to a specific N‑terminal motif on mature ALAS1 triggers conformational changes that favor its recognition and proteolytic degradation by mitochondrial ATP‑dependent proteases such as LONP1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and by the ClpXP complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Clinically, dysregulation of ALAS1 is implicated in acute hepatic porphyrias, where exacerbated induction of ALAS1 leads to accumulation of neurotoxic porphyrin precursors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In conditions such as frataxin deficiency, secondary heme shortage triggers compensatory upregulation of ALAS1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", while in drug‑induced settings, enhancer elements in the ALAS1 gene mediate xenobiotic responses through nuclear receptor activation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies highlight that ALAS1 functions as a metabolic integrator – linking transcriptional regulatory networks, mitochondrial heme production, and proteolytic turnover – to fine‑tune heme availability in response to physiological and pharmacological stimuli.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maryam Rakhshandehroo, Guido Hooiveld, Michael Müller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0006796"}], "href": "https://doi.org/10.1371/journal.pone.0006796"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19710929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19710929"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lotte Leick, Jørgen F P Wojtaszewski, Sune T Johansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00666.2007"}], "href": "https://doi.org/10.1152/ajpendo.00666.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18073319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18073319"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Di Shao, Yang Liu, Xiaojun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PGC-1 beta-regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERR alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2010.05.012"}], "href": "https://doi.org/10.1016/j.mito.2010.05.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20561910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20561910"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jennifer L Estall, Jorge L Ruas, Cheol Soo Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PGC-1alpha negatively regulates hepatic FGF21 expression by modulating the heme/Rev-Erb(alpha) axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0912533106"}], "href": "https://doi.org/10.1073/pnas.0912533106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20018698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20018698"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Naresh Kumar, Laura A Solt, Yongjun Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of adipogenesis by natural and synthetic REV-ERB ligands."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2009-0800"}], "href": "https://doi.org/10.1210/en.2009-0800"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20427485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20427485"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Qing Tian, Ting Li, Weihong Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.215772"}], "href": "https://doi.org/10.1074/jbc.M110.215772"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21659532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21659532"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yoshiko Kubota, Kazumi Nomura, Yasutake Katoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Mechanisms for Heme-dependent Degradation of ALAS1 Protein as a Component of Negative Feedback Regulation of Heme Biosynthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.719161"}], "href": "https://doi.org/10.1074/jbc.M116.719161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27496948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27496948"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Makiko Yasuda, Lin Gan, Brenden Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1406228111"}], "href": "https://doi.org/10.1073/pnas.1406228111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24821812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24821812"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chunye Lu, Gino Cortopassi "}, {"type": "b", "children": [{"type": "t", "text": "Frataxin knockdown causes loss of cytoplasmic iron-sulfur cluster functions, redox alterations and induction of heme transcripts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.abb.2006.09.010"}], "href": "https://doi.org/10.1016/j.abb.2006.09.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17098208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17098208"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "David J Fraser, Adrian Zumsteg, Urs A Meyer "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear receptors constitutive androstane receptor and pregnane X receptor activate a drug-responsive enhancer of the murine 5-aminolevulinic acid synthase gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M306148200"}], "href": "https://doi.org/10.1074/jbc.M306148200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12881517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12881517"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Nicholas J Lodato, Tisha Melia, Andy Rampersaud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sex-Differential Responses of Tumor Promotion-Associated Genes and Dysregulation of Novel Long Noncoding RNAs in Constitutive Androstane Receptor-Activated Mouse Liver."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/toxsci/kfx114"}], "href": "https://doi.org/10.1093/toxsci/kfx114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28903501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28903501"}]}]}]}
Synonyms	ALAS3, MIG4, ALAS, ALAS-H, ALASH
Proteins	HEM1_HUMAN
NCBI Gene ID	211
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ALAS1 has 8,326 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 130 datasets.

Click the + buttons to view associations for ALAS1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ALAS1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by ALAS1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ALAS1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ALAS1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of ALAS1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ALAS1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ALAS1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ALAS1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving ALAS1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ALAS1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ALAS1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ALAS1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ALAS1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ALAS1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ALAS1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ALAS1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ALAS1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ALAS1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ALAS1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ALAS1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ALAS1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ALAS1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ALAS1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ALAS1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ALAS1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ALAS1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ALAS1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ALAS1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ALAS1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ALAS1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ALAS1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ALAS1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ALAS1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for ALAS1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ALAS1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ALAS1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ALAS1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ALAS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ALAS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ALAS1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ALAS1 gene from the ENCODE Histone Modification Site Profiles dataset.