LIAS lipoic acid synthetase [Homo sapiens (human)] - Gene

Summary

Official Symbol: LIASprovided by HGNC
Official Full Name: lipoic acid synthetaseprovided by HGNC
Primary source: HGNC:HGNC:16429
See related: Ensembl:ENSG00000121897 MIM:607031; AllianceGenome:HGNC:16429
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: LS; LAS; LIP1; PDHLD; HGCLAS; HUSSY-01
Summary: The protein encoded by this gene belongs to the biotin and lipoic acid synthetases family. Localized in the mitochondrion, this iron-sulfur enzyme catalyzes the final step in the de novo pathway for the biosynthesis of lipoic acid, a potent antioxidant. The deficient expression of this enzyme has been linked to conditions such as diabetes, atherosclerosis and neonatal-onset epilepsy. Alternative splicing occurs at this locus, and several transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Aug 2020]
Expression: Ubiquitous expression in testis (RPKM 5.3), ovary (RPKM 4.0) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 4p14

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (39459056..39479506)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (39428708..39449155)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (39460676..39481126)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues 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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

FDX1 regulates cellular protein lipoylation through direct binding to LIAS.
Title: FDX1 regulates cellular protein lipoylation through direct binding to LIAS.
Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly.
Title: Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly.
this study used a bioinformatics approach to predict its structure. . A homology model for LIAS protein was generated using X-ray crystallographic structure of Thermosynechococcus elogatsu. The active site of LIAS protein was mapped and docked with S-Adenosyl Methionine
Title: Homology modeling of Homo sapiens lipoic acid synthase: Substrate docking and insights on its binding mode.
oxoglutarate dehydrogenase (OGDH) and lipoic acid synthase (LIAS), which when mutated stabilize HIF1alpha in a non-hydroxylated form.
Title: Mitochondrial Protein Lipoylation and the 2-Oxoglutarate Dehydrogenase Complex Controls HIF1α Stability in Aerobic Conditions.
heterozygous mutations (c.738-2A>G and c.929T>C (p.Met310Thr)) in LIAS.
Title: Novel compound heterozygous LIAS mutations cause glycine encephalopathy.
Patients with LIAS nonketotic hyperglycinemia varied in disease severity and cortical involvement.
Title: Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5.
We identified the homozygous mutation c.746G>A (p.Arg249His) in LIAS in an individual with neonatal-onset epilepsy, muscular hypotonia, lactic acidosis, and elevated glycine concentration in plasma and urine
Title: Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
Lipoic acid synthetase deficiency results in an overall disturbance in the antioxidant defense network, leading to increased inflammation, insulin resistance, and mitochondrial dysfunction.
Title: Lipoic acid synthase (LASY): a novel role in inflammation, mitochondrial function, and insulin resistance.

Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

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
Lipoic acid synthetase deficiency MedGen: C3280887 OMIM: 614462 GeneReviews: Not available	Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

LIAS_9211 (e-PCR)
- UniSTS:468077

D15S1477 (e-PCR)
- UniSTS:474482

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables lipoate synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables lipoate synthase activity	ISS Inferred from Sequence or Structural Similarity more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in lipoate biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in lipoate biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in neural tube closure	IEA Inferred from Electronic Annotation more info
involved_in protein lipoylation	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to oxidative stress	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Go to the top of the page Help

Preferred Names: lipoyl synthase, mitochondrial

Names: lip-syn; lipoate synthase

NP_001265519.1

EC 2.8.1.8

NP_001265520.1

EC 2.8.1.8

NP_001265521.1

EC 2.8.1.8

NP_001350629.1

EC 2.8.1.8

NP_006850.2

EC 2.8.1.8

NP_919433.1

EC 2.8.1.8

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_032111.1 RefSeqGene

Range

5012..25462

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001278590.2 → NP_001265519.1 lipoyl synthase, mitochondrial isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame coding exon, compared to variant 1. The resulting isoform (3) lacks an internal segment, compared to isoform 1.

Source sequence(s)

AC021148, AK026289, AK292238, AL528262, BC023635

Consensus CDS

CCDS63950.1

UniProtKB/Swiss-Prot

O43766

Related

ENSP00000371270.1, ENST00000381846.2

Conserved Domains (1) summary

PLN02428
Location:22 → 327

PLN02428; lipoic acid synthase
NM_001278591.2 → NP_001265520.1 lipoyl synthase, mitochondrial isoform 4 precursor

See identical proteins and their annotated locations for NP_001265520.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks several exons and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (4) is much shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AK292238, BF434814

Consensus CDS

CCDS87217.1

UniProtKB/TrEMBL

A0A1W2PQS9, Q6P5Q6

Related

ENSP00000491086.1, ENST00000424936.6

Conserved Domains (1) summary

pfam16881
Location:15 → 111

LIAS_N; N-terminal domain of lipoyl synthase of Radical_SAM family
NM_001278592.2 → NP_001265521.1 lipoyl synthase, mitochondrial isoform 5 precursor

See identical proteins and their annotated locations for NP_001265521.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks several exons and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (5) is much shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AI373464, AK292238

Consensus CDS

CCDS87220.1

UniProtKB/TrEMBL

A0A1W2PQ87, B4E0L7

Related

ENSP00000492833.1, ENST00000509519.5

Conserved Domains (1) summary

pfam16881
Location:15 → 73

LIAS_N; N-terminal domain of lipoyl synthase of Radical_SAM family
NM_001363700.2 → NP_001350629.1 lipoyl synthase, mitochondrial isoform 6 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks three alternate coding exons compared to variant 1. The resulting isoform (6) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC021148

Consensus CDS

CCDS87218.1

UniProtKB/TrEMBL

A0A1X7SBR7, D6RCP8

Related

ENSP00000261434.4, ENST00000261434.8

Conserved Domains (2) summary

PLN02428
Location:101 → 267

PLN02428; lipoic acid synthase

pfam16881
Location:15 → 73

LIAS_N; N-terminal domain of lipoyl synthase of Radical_SAM family
NM_006859.4 → NP_006850.2 lipoyl synthase, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_006850.2

Status: REVIEWED

Description

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

Source sequence(s)

AC021148, AK026289, AK292238, BC023635

Consensus CDS

CCDS3453.1

UniProtKB/Swiss-Prot

A8K873, C9JCF6, O43766, Q8IV62

UniProtKB/TrEMBL

A0A1W2PPM2

Related

ENSP00000492260.1, ENST00000640888.2

Conserved Domains (1) summary

PLN02428
Location:22 → 370

PLN02428; lipoic acid synthase
NM_194451.3 → NP_919433.1 lipoyl synthase, mitochondrial isoform 2 precursor

See identical proteins and their annotated locations for NP_919433.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate exon in the 3' coding region, compared to variant 1. The resulting isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC021148, AK026289, AK292238, BC023635

Consensus CDS

CCDS3454.1

UniProtKB/TrEMBL

A0A1W2PNQ5

Related

ENSP00000340676.2, ENST00000340169.7

Conserved Domains (1) summary

PLN02428
Location:22 → 319

PLN02428; lipoic acid synthase