ALAS2 5'-aminolevulinate synthase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALAS2provided by HGNC
Official Full Name: 5'-aminolevulinate synthase 2provided by HGNC
Primary source: HGNC:HGNC:397
See related: Ensembl:ENSG00000158578 MIM:301300; AllianceGenome:HGNC:397
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: ASB; ANH1; XLSA; ALASE; XLDPP; XLEPP; ALAS-E; SIDBA1
Summary: The product of this gene specifies an erythroid-specific mitochondrially located enzyme. The encoded protein catalyzes the first step in the heme biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive sideroblastic anemia. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Expression: Restricted expression toward bone marrow (RPKM 181.6) See more
Orthologs: mouse all
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Genomic context

Location:: Xp11.21

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (55009055..55030977, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (54302181..54324103, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (55035488..55057410, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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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?

Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis.
Title: Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis.
A synonymous coding variant that alters ALAS2 splicing and causes X-linked sideroblastic anemia.
Title: A synonymous coding variant that alters ALAS2 splicing and causes X-linked sideroblastic anemia.
Severe iron overload in a woman with homeostatic iron regulator (HFE) and a novel 5'-aminolevulinate synthase 2 (ALAS2) mutations: interactions of multiple genetic determinants.
Title: Severe iron overload in a woman with homeostatic iron regulator (HFE) and a novel 5'-aminolevulinate synthase 2 (ALAS2) mutations: interactions of multiple genetic determinants.
A mutation in the iron-responsive element of ALAS2 is a modifier of disease severity in a patient suffering from CLPX associated erythropoietic protoporphyria.
Title: A mutation in the iron-responsive element of ALAS2 is a modifier of disease severity in a patient suffering from CLPX associated erythropoietic protoporphyria.
Novel mutations in the ALAS2 gene from patients with X-linked sideroblastic anemia.
Title: Novel mutations in the ALAS2 gene from patients with X-linked sideroblastic anemia.
[Knockdown of ALAS2 Affects Erythroid Differentiation by Down-regulating Mitophagy Receptor BNIP3L].
Title: [Knockdown of ALAS2 Affects Erythroid Differentiation by Down-regulating Mitophagy Receptor BNIP3L].
Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release.
Title: Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release.
In erythropoietic protoporphyria, ALAS2 mRNA was increased both in absolute terms and in relation to deficiency in ferrochelatase mRNA as shown in this study.
Title: Delta-aminolevulinic acid synthase 2 expression in combination with iron as modifiers of disease severity in erythropoietic protoporphyria.
A novel mutation, c.1108G > A (p.A370T, NM_000032), was found in the ALAS2 gene located in exon 8. A mother with X-linked sideroblastic anemia and her so-far asymptomatic daughter were heterozygous for this mutation.
Title: Identification of a novel heterozygous ALAS2 mutation in a young Chinese female with X-linked sideroblastic anemia.
Patients with porphyrias should always be assessed for the presence of the ALAS2 gain-of-function modifier variants identified here. A key region of the ALAS2 carboxyterminal region is identified by the truncation mutations, and the correlation of increased thermolability with activity suggests that increased molecular flexibility/active site openness is the mechanism of enhanced function of mutations in this region.
Title: Molecular expression, characterization and mechanism of ALAS2 gain-of-function mutants.

Submit: New GeneRIF Correction See all GeneRIFs (46)

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
X-linked erythropoietic protoporphyria MedGen: C2677889 OMIM: 300752 GeneReviews: X-Linked Protoporphyria	Compare labs
X-linked sideroblastic anemia 1 MedGen: C4551511 OMIM: 300751 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

WI-16860 (e-PCR)
- UniSTS:2091

A009V31 (e-PCR)
- UniSTS:2092

RH94266 (e-PCR)
- UniSTS:90022

GDB:193183 (e-PCR)
- UniSTS:44991

AL023933 (e-PCR)
- UniSTS:12483

WI-12678 (e-PCR)
- UniSTS:15052

SGC33540 (e-PCR)
- UniSTS:68045

G32884 (e-PCR)
- UniSTS:117463

RH16577 (e-PCR)
- UniSTS:27882

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 5-aminolevulinate synthase activity	IMP Inferred from Mutant Phenotype 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 erythrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in erythrocyte differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in heme biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in heme biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in heme biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
involved_in hemoglobin biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in hemoglobin biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular iron ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular oxygen homeostasis	NAS Non-traceable Author Statement more info	PubMed
involved_in protoporphyrinogen IX biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
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	PubMed

General protein information

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

Names: 5-aminolevulinic acid synthase 2; aminolevulinate, delta-, synthase 2; delta-ALA synthase 2; delta-ALA synthetase; delta-aminolevulinate synthase 2; erythroid-specific delta-aminolevulinate synthase

NP_000023.2

EC 2.3.1.37

NP_001033056.1

EC 2.3.1.37

NP_001033057.1

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.

Genomic

NG_008983.1 RefSeqGene

Range

5088..27010

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_1163

mRNA and Protein(s)

NM_000032.5 → NP_000023.2 5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform a precursor

See identical proteins and their annotated locations for NP_000023.2

Status: REVIEWED

Description

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

Source sequence(s)

AK313118, BQ182291

Consensus CDS

CCDS14366.1

UniProtKB/Swiss-Prot

A8K3F0, A8K6C4, P22557, Q13735, Q5JZF5, Q8N6H3

Related

ENSP00000497236.1, ENST00000650242.1

Conserved Domains (3) summary

COG0156
Location:143 → 534

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

TIGR01821
Location:143 → 548

5aminolev_synth; 5-aminolevulinic acid synthase

pfam09029
Location:5 → 100

Preseq_ALAS; 5-aminolevulinate synthase presequence
NM_001037967.4 → NP_001033056.1 5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform b precursor

See identical proteins and their annotated locations for NP_001033056.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in an isoform (b) that is shorter than isoform a.

Source sequence(s)

AK291589, BQ182291

Consensus CDS

CCDS35303.1

UniProtKB/Swiss-Prot

P22557

Related

ENSP00000337131.4, ENST00000335854.8

Conserved Domains (3) summary

COG0156
Location:106 → 497

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

TIGR01821
Location:106 → 511

5aminolev_synth; 5-aminolevulinic acid synthase

pfam09029
Location:5 → 100

Preseq_ALAS; 5-aminolevulinate synthase presequence
NM_001037968.4 → NP_001033057.1 5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform c precursor

See identical proteins and their annotated locations for NP_001033057.1

Status: REVIEWED

Description

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

Source sequence(s)

AL020991, BP233279, BQ182291

Consensus CDS

CCDS43960.1

UniProtKB/Swiss-Prot

P22557

Related

ENSP00000379501.3, ENST00000396198.7

Conserved Domains (3) summary

COG0156
Location:130 → 521

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

TIGR01821
Location:130 → 535

5aminolev_synth; 5-aminolevulinic acid synthase

pfam09029
Location:29 → 124

Preseq_ALAS; 5-aminolevulinate synthase presequence

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_000023.11 Reference GRCh38.p14 Primary Assembly

Range

55009055..55030977 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060947.1 Alternate T2T-CHM13v2.0

Range

54302181..54324103 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001037969.2: Suppressed sequence

Description

NM_001037969.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.