LTA lymphotoxin alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: LTAprovided by HGNC
Official Full Name: lymphotoxin alphaprovided by HGNC
Primary source: HGNC:HGNC:6709
See related: Ensembl:ENSG00000226979 MIM:153440; AllianceGenome:HGNC:6709
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: LT; TNFB; TNFSF1; TNLG1E
Summary: The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]
Expression: Biased expression in lymph node (RPKM 3.5), appendix (RPKM 1.7) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.33

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (31560610..31574324)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (31424599..31427376)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (31539876..31542101)

Chromosome 6 - NC_000006.12 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Combined tumor necrosis factor-alpha (-308 G/A) and tumor necrosis factor-beta (+ 252 A/G) nucleotide polymorphisms and chronicity in Egyptian children with immune thrombocytopenia.
Title: Combined tumor necrosis factor-α (-308 G/A) and tumor necrosis factor-β (+ 252 A/G) nucleotide polymorphisms and chronicity in Egyptian children with immune thrombocytopenia.
Prognostic significance of the genetic variant of lymphotoxin alpha (p.Thr60Asn) in egyptian patients with advanced hepatocellular carcinoma.
Title: Prognostic significance of the genetic variant of lymphotoxin alpha (p.Thr60Asn) in egyptian patients with advanced hepatocellular carcinoma.
Association of LTA and SOD Gene Polymorphisms with Cerebral White Matter Hyperintensities in Migraine Patients.
Title: Association of LTA and SOD Gene Polymorphisms with Cerebral White Matter Hyperintensities in Migraine Patients.
Genetic polymorphism of tumor necrosis factor alpha (TNF-alpha) and tumor necrosis factor beta (TNF-beta) genes and risk of oral pre-cancer and cancer in North Indian population.
Title: Genetic polymorphism of tumor necrosis factor alpha (TNF-α) and tumor necrosis factor beta (TNF-β) genes and risk of oral pre-cancer and cancer in North Indian population.
Polymorphisms of the TNF, LTA, and TNFRSF1B genes are associated with onsets of menarche and menopause in US women of European ancestry.
Title: Polymorphisms of the TNF, LTA, and TNFRSF1B genes are associated with onsets of menarche and menopause in US women of European ancestry.
Genetic Variation on TNF/LTA and TNFRSF1A Genes is Associated with Outcomes of Hepatitis C Virus Infection.
Title: Genetic Variation on TNF/LTA and TNFRSF1A Genes is Associated with Outcomes of Hepatitis C Virus Infection.
Association between tumor necrosis factor alpha and lymphotoxin alpha gene polymorphisms and migraine occurrence among Jordanians.
Title: Association between tumor necrosis factor alpha and lymphotoxin alpha gene polymorphisms and migraine occurrence among Jordanians.
Association of lymphotoxin-alpha gene polymorphisms (rs909253, rs1800683 and rs2229094) and risk of large-artery atherosclerosis stroke in Iranian population.
Title: Association of lymphotoxin-alpha gene polymorphisms (rs909253, rs1800683 and rs2229094) and risk of large-artery atherosclerosis stroke in Iranian population.
Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA.
Title: Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA.
Elevated lymphotoxin-alpha (TNFbeta) is associated with intervertebral disc degeneration.
Title: Elevated lymphotoxin-α (TNFβ) is associated with intervertebral disc degeneration.

Submit: New GeneRIF Correction See all GeneRIFs (244)

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
Leprosy, susceptibility to, 4 MedGen: C1970254 OMIM: 610988 GeneReviews: Not available	not available
Myocardial infarction, susceptibility to MedGen: C1832662 OMIM: 608446 GeneReviews: Not available	not available
Psoriatic arthritis, susceptibility to MedGen: C1835223 OMIM: 607507 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of candidate loci at 6p21 and 21q22 in a genome-wide association study of cardiac manifestations of neonatal lupus. 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)

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	In endometrial epithelium-derived cells, gp120 from CCR5-tropic HIV-1 increases the release of monocytes/chemokines-attracting chemokines (IL-8 and GRO) and proinflammatory cytokines (TNF-beta and IL-1alpha)	PubMed
Tat	tat	HIV-1 Tat101 upregulates the expression of lymphotoxin alpha (LTA; TNFB) in Jurkat cells	PubMed
	tat	HIV-1 Tat downregulates TNF-beta expression in central nervous system-derived glial cells, suggesting a novel mechanism whereby HIV-1 is able to establish latent infection of glial cells	PubMed
	tat	HIV-1 Tat upregulates TNF-beta expression through binding to a TAR-like RNA structure in the TNF-beta promoter	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH17367 (e-PCR)
- UniSTS:56874

GDB:192948 (e-PCR)
- UniSTS:155729

RH71008 (e-PCR)
- UniSTS:53844

LTA_189 (e-PCR)
- UniSTS:277457

PMC32163P1 (e-PCR)
- UniSTS:273125

GDB:182383 (e-PCR)
- UniSTS:155378

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	IEA Inferred from Electronic Annotation more info
enables signaling receptor binding	TAS Traceable Author Statement more info	PubMed
enables tumor necrosis factor receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in activation of NF-kappaB-inducing kinase activity	NAS Non-traceable Author Statement more info	PubMed
involved_in apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in cell communication	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within defense response to Gram-positive bacterium	IEA Inferred from Electronic Annotation more info
involved_in dendritic cell homeostasis	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within humoral immune response	IEA Inferred from Electronic Annotation more info
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lymph node development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of chronic inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of extrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of glial cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of humoral immune response mediated by circulating immunoglobulin	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of type II interferon production	IEA Inferred from Electronic Annotation more info
involved_in regulation of necroptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of type I interferon production	NAS Non-traceable Author Statement more info	PubMed
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in signaling	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular region	IEA Inferred from Electronic Annotation more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IPI Inferred from Physical Interaction more info	PubMed
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of tumor necrosis factor receptor superfamily complex	IPI Inferred from Physical Interaction more info	PubMed
part_of tumor necrosis factor receptor superfamily complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: lymphotoxin-alpha

Names: LT-alpha; TNF superfamily, member 1; TNF-beta; tumor necrosis factor beta; tumor necrosis factor ligand 1E; tumor necrosis factor ligand superfamily member 1

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_012010.2 RefSeqGene

Range

16681..18716

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000595.4 → NP_000586.2 lymphotoxin-alpha precursor

See identical proteins and their annotated locations for NP_000586.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AL662801, BG685356, BX108399, D12614

Consensus CDS

CCDS4701.1

UniProtKB/Swiss-Prot

P01374, Q8N4C3, Q9UKS8

UniProtKB/TrEMBL

A0A1U9X7Z3, Q5HYS4, Q5STV3

Related

ENSP00000413450.2, ENST00000418386.3

Conserved Domains (1) summary

cd00184
Location:63 → 203

TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...
NM_001159740.2 → NP_001153212.1 lymphotoxin-alpha precursor

See identical proteins and their annotated locations for NP_001153212.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

BP338937, BX108399, D12614

Consensus CDS

CCDS4701.1

UniProtKB/Swiss-Prot

P01374, Q8N4C3, Q9UKS8

UniProtKB/TrEMBL

A0A1U9X7Z3, Q5HYS4, Q5STV3

Related

ENSP00000403495.1, ENST00000454783.5

Conserved Domains (1) summary

cd00184
Location:63 → 203

TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...