ALAD aminolevulinate dehydratase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALADprovided by HGNC
Official Full Name: aminolevulinate dehydrataseprovided by HGNC
Primary source: HGNC:HGNC:395
See related: Ensembl:ENSG00000148218 MIM:125270; AllianceGenome:HGNC:395
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
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. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
Expression: Ubiquitous expression in adrenal (RPKM 60.0), liver (RPKM 56.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q32

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (113386312..113401284, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (125585129..125600114, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (116148592..116163564, complement)

Chromosome 9 - NC_000009.12 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?

ALAD and APOE polymorphisms are associated with lead and mercury levels in Italian pregnant women and their newborns with adequate nutritional status of zinc and selenium.
Title: ALAD and APOE polymorphisms are associated with lead and mercury levels in Italian pregnant women and their newborns with adequate nutritional status of zinc and selenium.
Genetic Polymorphism of Delta Aminolevulinic Acid Dehydratase (ALAD) Gene and Symptoms of Chronic Mercury Exposure in Munduruku Indigenous Children within the Brazilian Amazon.
Title: Genetic Polymorphism of Delta Aminolevulinic Acid Dehydratase (ALAD) Gene and Symptoms of Chronic Mercury Exposure in Munduruku Indigenous Children within the Brazilian Amazon.
Activity of the enzyme delta-aminolevulinate dehydratase and parameters of oxidative stress in different modes of delivery.
Title: Activity of the enzyme delta-aminolevulinate dehydratase and parameters of oxidative stress in different modes of delivery.
Genetic susceptibility of delta-ALAD associated with lead (Pb) intoxication: sources of exposure, preventive measures, and treatment interventions.
Title: Genetic susceptibility of δ-ALAD associated with lead (Pb) intoxication: sources of exposure, preventive measures, and treatment interventions.
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.
Heme biosynthesis depends on previously unrecognized acquisition of iron-sulfur cofactors in human amino-levulinic acid dehydratase.
Title: Heme biosynthesis depends on previously unrecognized acquisition of iron-sulfur cofactors in human amino-levulinic acid dehydratase.
Pb blood variability was found associated with ALAD polymorphisms (SNPs rs1805313, rs1800435)
Title: Trace elements and ALAD gene polymorphisms in general population from three uranium legacy sites - A case study in Kyrgyzstan.
aminolevulinate dehydratase genotype may be a susceptibility factor for the effects of lead on child growth
Title: Effects of ALAD genotype on the relationship between lead exposure and anthropometry in a Cohort of Mexican children.
delta-Aminolevulinic Acid Dehydratase gene polymorphism may be an effect modifier and a marker of genetic susceptibility to lead toxicity.
Title: Effects of delta-Aminolevulinic Acid Dehydratase Gene Polymorphism on Hematological Parameters and Kidney Function of Lead-exposed Workers.
Automobile paints workers with ALAD 1-2 genotype showed the positive association of blood lead levels with diastolic blood pressure whereas, a genotypic combination of ALAD 1-2/VDR BB showed the negative association of serum uric acid with BLL.
Title: Role of ALAD and VDR genotypes on the association of low blood lead level with serum uric acid and blood pressure in automobile paint workers of Karachi, Pakistan.

Submit: New GeneRIF Correction See all GeneRIFs (72)

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

Associated conditions

Description	Tests
Porphobilinogen synthase deficiency MedGen: C0268328 OMIM: 612740 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH67978 (e-PCR)
- UniSTS:87815

G67280 (e-PCR)
- UniSTS:186413

G67279 (e-PCR)
- UniSTS:186414

G67281 (e-PCR)
- UniSTS:186415

G67282 (e-PCR)
- UniSTS:186416

G67283 (e-PCR)
- UniSTS:186417

G67278 (e-PCR)
- UniSTS:186418

STS-X64467 (e-PCR)
- UniSTS:66355

MARC_17135-17136:1021046712:3 (e-PCR)
- UniSTS:268231

RH71467 (e-PCR)
- UniSTS:3529

GDB:182364 (e-PCR)
- UniSTS:155375

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables catalytic activity	TAS Traceable Author Statement more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables porphobilinogen synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables porphobilinogen synthase activity	IDA Inferred from Direct Assay more info	PubMed
enables proteasome core complex binding	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to interleukin-4	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lead ion	IEA Inferred from Electronic Annotation 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 heme biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of proteasomal protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein homooligomerization	IPI Inferred from Physical Interaction more info	PubMed
involved_in protoporphyrinogen IX biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in response to activity	IEA Inferred from Electronic Annotation more info
involved_in response to aluminum ion	IEA Inferred from Electronic Annotation more info
involved_in response to amino acid	IEA Inferred from Electronic Annotation more info
involved_in response to arsenic-containing substance	IEA Inferred from Electronic Annotation more info
involved_in response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in response to cobalt ion	IEA Inferred from Electronic Annotation more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to fatty acid	IEA Inferred from Electronic Annotation more info
involved_in response to glucocorticoid	IEA Inferred from Electronic Annotation more info
involved_in response to herbicide	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to ionizing radiation	IEA Inferred from Electronic Annotation more info
involved_in response to iron ion	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to mercury ion	IEA Inferred from Electronic Annotation more info
involved_in response to methylmercury	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in response to platinum ion	IEA Inferred from Electronic Annotation more info
involved_in response to selenium ion	IEA Inferred from Electronic Annotation more info
involved_in response to vitamin B1	IEA Inferred from Electronic Annotation more info
involved_in response to vitamin E	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to zinc ion	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed
located_in secretory granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: delta-aminolevulinic acid dehydratase

Names: aminolevulinate, delta-, dehydratase; porphobilinogen synthase; testicular tissue protein Li 95

NP_000022.3

EC 4.2.1.24

NP_001003945.1

EC 4.2.1.24

NP_001304674.1

EC 4.2.1.24

XP_011516666.1

EC 4.2.1.24

XP_047278900.1

EC 4.2.1.24

XP_047278901.1

EC 4.2.1.24

XP_047278902.1

EC 4.2.1.24

XP_047278903.1

EC 4.2.1.24

XP_054218281.1

EC 4.2.1.24

XP_054218282.1

EC 4.2.1.24

XP_054218283.1

EC 4.2.1.24

XP_054218284.1

EC 4.2.1.24

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.

Genomic

NG_008716.1 RefSeqGene

Range

5055..20027

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000031.6 → NP_000022.3 delta-aminolevulinic acid dehydratase isoform b

See identical proteins and their annotated locations for NP_000022.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a segment of the coding region and initiates translation from an alternate start codon, compared to variant 1. The resulting isoform (b) has a distinct N-terminus, compared to isoform a.

Source sequence(s)

AK131490, AK290490, BC000977, BU625796, DA805310

Consensus CDS

CCDS6794.2

UniProtKB/Swiss-Prot

A8K375, B2R6F2, P13716, Q16870, Q16871, Q9BVQ9

UniProtKB/TrEMBL

A0A140VJL9, B7Z3I9

Related

ENSP00000386284.3, ENST00000409155.8

Conserved Domains (1) summary

cd04824
Location:8 → 327

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 ...
NM_001003945.3 → NP_001003945.1 delta-aminolevulinic acid dehydratase isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript, and encodes the longest isoform (a).

Source sequence(s)

AK131490, AK290490, BU625796

UniProtKB/TrEMBL

Q6ZMU0

Related

ENST00000482847.5

Conserved Domains (1) summary

cd04824
Location:68 → 356

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 ...
NM_001317745.2 → NP_001304674.1 delta-aminolevulinic acid dehydratase isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks an alternate in-frame exon in the 5' coding region and initiates translation from an alternate start codon, compared to variant 1. The resulting isoform (c) has a distinct N-terminus compared to isoform a.

Source sequence(s)

AK131490, AK295945, BU625796

UniProtKB/TrEMBL

B7Z3I9

Conserved Domains (1) summary

cd04824
Location:17 → 319

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: 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_000009.12 Reference GRCh38.p14 Primary Assembly

Range

113386312..113401284 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047422947.1 → XP_047278903.1 delta-aminolevulinic acid dehydratase isoform X4
XM_011518364.3 → XP_011516666.1 delta-aminolevulinic acid dehydratase isoform X3

See identical proteins and their annotated locations for XP_011516666.1

UniProtKB/TrEMBL

B7Z3I9

Conserved Domains (1) summary

cd04824
Location:17 → 336

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 ...
XM_047422944.1 → XP_047278900.1 delta-aminolevulinic acid dehydratase isoform X1
XM_047422945.1 → XP_047278901.1 delta-aminolevulinic acid dehydratase isoform X1
XM_047422946.1 → XP_047278902.1 delta-aminolevulinic acid dehydratase isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060933.1 Alternate T2T-CHM13v2.0

Range

125585129..125600114 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054362307.1 → XP_054218282.1 delta-aminolevulinic acid dehydratase isoform X1
XM_054362309.1 → XP_054218284.1 delta-aminolevulinic acid dehydratase isoform X3
XM_054362306.1 → XP_054218281.1 delta-aminolevulinic acid dehydratase isoform X1
XM_054362308.1 → XP_054218283.1 delta-aminolevulinic acid dehydratase isoform X2