ALAS1 5'-aminolevulinate synthase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALAS1provided by HGNC
Official Full Name: 5'-aminolevulinate synthase 1provided by HGNC
Primary source: HGNC:HGNC:396
See related: Ensembl:ENSG00000023330 MIM:125290; AllianceGenome:HGNC:396
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ALAS; MIG4; ALAS3; ALASH; ALAS-H
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 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]
Expression: Biased expression in adrenal (RPKM 297.6), liver (RPKM 180.6) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.2

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (52198083..52214327)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (52230963..52247212)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (52232099..52248343)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Heme-dependent recognition of 5-aminolevulinate synthase by the human mitochondrial molecular chaperone ClpX.
Title: Heme-dependent recognition of 5-aminolevulinate synthase by the human mitochondrial molecular chaperone ClpX.
5-Aminolevulinate dehydratase porphyria: Update on hepatic 5-aminolevulinic acid synthase induction and long-term response to hemin.
Title: 5-Aminolevulinate dehydratase porphyria: Update on hepatic 5-aminolevulinic acid synthase induction and long-term response to hemin.
Inhibition of ALAS1 activity exerts anti-tumour effects on colorectal cancer in vitro.
Title: Inhibition of ALAS1 activity exerts anti-tumour effects on colorectal cancer in vitro.
The mutation in CLPX inactivates its ATPase activity, resulting in coassembly of mutant and WT protomers to form an enzyme with reduced activity. The presence of low-activity CLPX increases the posttranslational stability of ALAS, causing increased ALAS protein and ALA levels, leading to abnormal accumulation of PPIX.
Title: Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria.
the heme-binding site in the N-terminal region of the mature ALAS1 protein is also necessary for the heme-dependent oxidation of ALAS1.
Title: Novel Mechanisms for Heme-dependent Degradation of ALAS1 Protein as a Component of Negative Feedback Regulation of Heme Biosynthesis.
ALAS1 mRNA and activity were elevated approximately ~3- and 5-fold, and HMB synthase activity was approximately half-normal (~42%)
Title: Liver Transplantation for Acute Intermittent Porphyria: Biochemical and Pathologic Studies of the Explanted Liver.
The -853T variant functions as an enhancer in the presence of estrogen and speculates that the -1253A variant reduces transcription activity.
Title: Functional analysis of the 5' regulatory region of the 5-aminolevulinate synthase (ALAS1) gene in response to estrogen.
These results indicate that ALAS1 is a novel NR5A-target gene and participates in steroid hormone production.
Title: Nuclear receptor 5A (NR5A) family regulates 5-aminolevulinic acid synthase 1 (ALAS1) gene expression in steroidogenic cells.
Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells.
Title: Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells.
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association analysis identifies 13 new risk loci for schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of aminolevulinate, delta-, synthase 1 (ALAS1) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH69932 (e-PCR)
- UniSTS:3329

RH93452 (e-PCR)
- UniSTS:90989

RH77906 (e-PCR)
- UniSTS:40822

D2S1587E (e-PCR)
- UniSTS:150671

GDB:273584 (e-PCR)
- UniSTS:156360

SHGC-31564 (e-PCR)
- UniSTS:70364

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 5-aminolevulinate synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 5-aminolevulinate synthase activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables pyridoxal phosphate binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in erythrocyte development	IBA Inferred from Biological aspect of Ancestor more info
involved_in heme A biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in heme B biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in heme O biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in heme biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in hemoglobin biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in protoporphyrinogen IX biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in response to bile acid	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: 5-aminolevulinate synthase, non-specific, mitochondrial

Names: 5-aminolevulinate synthase, nonspecific, mitochondrial; 5-aminolevulinic acid synthase 1; aminolevulinate, delta-, synthase 1; delta-ALA synthase 1; delta-aminolevulinate synthase 1; migration-inducing protein 4

NP_000679.1

EC 2.3.1.37

NP_001291372.1

EC 2.3.1.37

NP_001291373.1

EC 2.3.1.37

NP_954635.1

EC 2.3.1.37

XP_011531779.1

EC 2.3.1.37

XP_011531780.1

EC 2.3.1.37

XP_016861362.1

EC 2.3.1.37

XP_054201640.1

EC 2.3.1.37

XP_054201641.1

EC 2.3.1.37

XP_054201642.1

EC 2.3.1.37

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_000688.6 → NP_000679.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_000679.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, and 3 encode the same protein.

Source sequence(s)

AI868691, AU279391, BC011798, CD014147, X56351

Consensus CDS

CCDS2847.1

UniProtKB/Swiss-Prot

P13196

UniProtKB/TrEMBL

A0A024R353, B4DVA0, Q5JAM2

Related

ENSP00000418779.1, ENST00000484952.6

Conserved Domains (2) summary

pfam09029
Location:2 → 137

Preseq_ALAS; 5-aminolevulinate synthase presequence

cl18945
Location:197 → 602

AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...
NM_001304443.1 → NP_001291372.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_001291372.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks an alternate exon and uses an alternate splice site in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same protein.

Source sequence(s)

AB063322, AK300993, BM546974, DA691060, Y00451

Consensus CDS

CCDS2847.1

UniProtKB/Swiss-Prot

P13196

UniProtKB/TrEMBL

A0A024R353, B4DVA0, Q5JAM2

Related

ENSP00000309259.2, ENST00000310271.6

Conserved Domains (2) summary

pfam09029
Location:2 → 137

Preseq_ALAS; 5-aminolevulinate synthase presequence

cl18945
Location:197 → 602

AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...
NM_001304444.1 → NP_001291373.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (4) uses an alternate splice site in its 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is longer than isoform 1.

Source sequence(s)

AB063322, AK300993, BM546974, DA691060

UniProtKB/TrEMBL

B4DVA0

Conserved Domains (3) summary

COG0156
Location:214 → 605

BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]

pfam09029
Location:19 → 154

Preseq_ALAS; 5-aminolevulinate synthase presequence

cl18945
Location:214 → 619

AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...
NM_199166.2 → NP_954635.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_954635.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate exon in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.

Source sequence(s)

AI868691, BM546974, BU173391, X56351

Consensus CDS

CCDS2847.1

UniProtKB/Swiss-Prot

P13196

UniProtKB/TrEMBL

A0A024R353, B4DVA0, Q5JAM2

Related

ENSP00000417719.1, ENST00000469224.5

Conserved Domains (2) summary

pfam09029
Location:2 → 137

Preseq_ALAS; 5-aminolevulinate synthase presequence

cl18945
Location:197 → 602

AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

52198083..52214327

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011533478.3 → XP_011531780.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform X2

UniProtKB/TrEMBL

B4DVA0

Conserved Domains (3) summary

COG0156
Location:214 → 550

BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]

pfam09029
Location:19 → 154

Preseq_ALAS; 5-aminolevulinate synthase presequence

cl18945
Location:214 → 564

AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...
XM_017005873.2 → XP_016861362.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform X3

UniProtKB/TrEMBL

B4DVA0

Conserved Domains (2) summary

pfam09029
Location:2 → 137

Preseq_ALAS; 5-aminolevulinate synthase presequence

cl18945
Location:197 → 547

AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...
XM_011533477.3 → XP_011531779.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform X1

UniProtKB/TrEMBL

B4DVA0

Conserved Domains (3) summary

COG0156
Location:214 → 604

BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]

pfam09029
Location:19 → 154

Preseq_ALAS; 5-aminolevulinate synthase presequence

cl18945
Location:214 → 603

AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

52230963..52247212

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054345666.1 → XP_054201641.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform X2
XM_054345667.1 → XP_054201642.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform X3
XM_054345665.1 → XP_054201640.1 5-aminolevulinate synthase, non-specific, mitochondrial isoform X1