ALAD aminolevulinate dehydratase [Homo sapiens] - Gene

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Summary

Official Symbol: ALADprovided by HGNC
Official Full Name: aminolevulinate dehydrataseprovided by HGNC
Primary source: HGNC:395
Locus tag: RP11-10I9.1
See related: Ensembl:ENSG00000148218; HPRD:00504; MIM:125270; Vega:OTTHUMG00000020522
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PBGS; ALADH; MGC5057
Summary: The ALAD enzyme is composed of 8 identical subunits and catalyzes the condensation of 2 molecules of delta-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). ALAD catalyzes the second step in the porphyrin and heme biosynthetic pathway; zinc is essential for enzymatic activity. ALAD enzymatic activity is inhibited by lead and a defect in the ALAD structural gene can cause increased sensitivity to lead poisoning and acute hepatic porphyria. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 9q33.1

Sequence :: Chromosome: 9; NC_000009.11 (116148592..116163618, complement)

See ALAD in Epigenomics, MapViewer

Chromosome 9 - NC_000009.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

ALAD genotype modifies the relationship between Pb and its toxic effects on the peripheral nervous system. This must be considered in the assessment of risks at Pb exposure.
Title: δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system.
association between oxidative stress, abnormalities on lipid profile, distribution of body fat and delta-ALA-D activity inhibition; the enzyme is more oxidized in the DM2 patient
Title: δ-Aminolevulinate dehydratase activity in type 2 diabetic patients and its association with lipid profile and oxidative stress.
ALAD2 and hPEPT2*2 polymorphisms may exaggerate Pb blood burden in boys.
Title: δ-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 and peptide transporter 2*2 haplotype may differentially mediate lead exposure in male children.
A common genetic variation in ALAD may alter the risk of renal cell carcinoma
Title: Comprehensive analysis of 5-aminolevulinic acid dehydrogenase (ALAD) variants and renal cell carcinoma risk among individuals exposed to lead.
Examined whether the ALAD G177C single nucleotide polymorphism (SNP) affects the relationship between lead and mortality; observed no convincing interaction effect between ALAD genotype and blood lead level on mortality risk.
Title: Blood lead levels, ALAD gene polymorphisms, and mortality.
Study suggests that the lead-exposure-induced increases in ALAD methylation may be involved in the mechanism of lead toxicity.
Title: Lead exposure suppressed ALAD transcription by increasing methylation level of the promoter CpG islands.
Lead-exposed workers with the ALAD2 allele appear to be more susceptible to the effects of lead on renal injury, whereas neurobehavioral functions in ALAD1 homozygote tend to be more vulnerable.
Title: Effect of the delta-aminolevulinic acid dehydratase gene polymorphism on renal and neurobehavioral function in workers exposed to lead in China.
blood lead levels may be an important risk factor for hypertension and increased systolic and diastolic blood pressure. These associations may be modified by ALAD genotype.
Title: Modification by ALAD of the association between blood lead and blood pressure in the U.S. population: results from the Third National Health and Nutrition Examination Survey.
ALAD has a major and limiting role in regulating protoporphyrin IX synthesis and photodynamic therapy outcome.
Title: Silencing of ALA dehydratase affects ALA-photodynamic therapy efficacy in K562 erythroleukemic cells.
Allosteric inhibition of human porphobilinogen synthase.
Title: Allosteric inhibition of human porphobilinogen synthase.

Submit: New GeneRIF Correction See all (39)

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Lead poisoning, susceptibility to

MIM: 612740

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
P13716	P13716	ALAD		HPRD	PubMed
BioGRID:106712	BioGRID:113164	UBC		BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
catalytic activity	TAS Traceable Author Statement more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
lead ion binding	IDA Inferred from Direct Assay more info	PubMed
lyase activity	IEA Inferred from Electronic Annotation more info
porphobilinogen synthase activity	IDA Inferred from Direct Assay more info	PubMed
porphobilinogen synthase activity	TAS Traceable Author Statement more info
zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
heme biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
heme biosynthetic process	TAS Traceable Author Statement more info
porphyrin-containing compound metabolic process	TAS Traceable Author Statement more info
protein homooligomerization	IPI Inferred from Physical Interaction more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info

General protein information

Preferred Names: delta-aminolevulinic acid dehydratase

Names: delta-aminolevulinic acid dehydratase; porphobilinogen synthase; aminolevulinate, delta-, dehydratase

NP_000022.3

EC 4.2.1.24

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NCBI Reference Sequences (RefSeq)

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.

Genomic

NG_008716.1 RefSeqGene

Range

5001..20027

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000031.5 → NP_000022.3 delta-aminolevulinic acid dehydratase

Status: REVIEWED

Source sequence(s)

AK131490, AK290490, BC000977, BU625796, DA412142, DA805310

Consensus CDS

CCDS6794.2

UniProtKB/Swiss-Prot

P13716

UniProtKB/TrEMBL

Q6ZMU0

Related

ENSP00000386284, OTTHUMP00000021953, ENST00000409155, OTTHUMT00000053724

Conserved Domains (1) summary

cd04824
Location:8 – 327
Blast Score: 1499

eu_ALAD_PBGS_cysteine_rich; Porphobilinogen synthase (PBGS), which is also called delta-aminolevulinic acid dehydratase (ALAD), catalyzes the condensation of two 5-aminolevulinic acid (ALA) molecules to form the pyrrole porphobilinogen (PBG), which is the second step in the ...

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000009.11 Reference GRCh37.p5 Primary Assembly

Range

116148592..116163618, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000141.1 Alternate HuRef

Range

85755612..85770551, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001003945.1: Suppressed sequence

Description

NM_001003945.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL137066.15	CAH70099.3
		CAX14973.1
		CAX14974.1
		CAX14975.1
genomic	AY319481.1	AAP72012.1
genomic	CH471090.1	EAW87379.1
		EAW87380.1
genomic	X64467.1	CAA45796.1
mRNA	AA593706.1	None
mRNA	AK131490.1	BAD18635.1
mRNA	AK290490.1	BAF83179.1
mRNA	AK295945.1	BAH12225.1
mRNA	AK312552.1	BAG35449.1
mRNA	AU279870.1	None
mRNA	BC000977.3	AAH00977.3
mRNA	BU625796.1	None
mRNA	BX494400.1	None
mRNA	DA412142.1	None
mRNA	DA805310.1	None
mRNA	M13928.1	AAA51687.1
mRNA	S99468.1	AAC60581.1
mRNA	S99471.1	AAC60582.1