LTB lymphotoxin beta [Homo sapiens (human)] - Gene

Summary

Official Symbol: LTBprovided by HGNC
Official Full Name: lymphotoxin betaprovided by HGNC
Primary source: HGNC:HGNC:6711
See related: Ensembl:ENSG00000227507 MIM:600978; AllianceGenome:HGNC:6711
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: p33; TNFC; TNFSF3; TNLG1C
Summary: Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Expression: Biased expression in spleen (RPKM 84.6), lymph node (RPKM 56.9) and 8 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.33

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (31580558..31582425, complement)
RS_2023_03	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (31433610..31435477, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (31548335..31550202, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

DNA methylation status of the SPHK1 and LTB genes underlies the clinicopathological diversity of non-alcoholic steatohepatitis-related hepatocellular carcinomas.
Title: DNA methylation status of the SPHK1 and LTB genes underlies the clinicopathological diversity of non-alcoholic steatohepatitis-related hepatocellular carcinomas.
Gastrointestinal Symptom Cluster is Associated With Epigenetic Regulation of Lymphotoxin Beta in Oncology Patients Receiving Chemotherapy.
Title: Gastrointestinal Symptom Cluster is Associated With Epigenetic Regulation of Lymphotoxin Beta in Oncology Patients Receiving Chemotherapy.
Combination of an EGFR tyrosine kinase inhibitor and a NF-kappaB inhibitor effectively suppressed cetuximab-resistant HNSCC and interfering with the EGFR-LTbeta interaction reverses resistance.
Title: Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer.
TNF is able to upregulate LT-beta expression in hepatic cells at the transcriptional level by the binding of NF-kappaB p50/p65 heterodimers and Ets1 to their respective sites in the LT-beta promoter.
Title: TNF-inducible expression of lymphotoxin-β in hepatic cells: an essential role for NF-κB and Ets1 transcription factors.
The multifaceted character of lymphotoxin beta may be involved in inflammatory myopathies and muscular dystrophies.
Title: The multifaceted character of lymphotoxin β in inflammatory myopathies and muscular dystrophies.
A strong association was found between several single nucleotide polymorphisms in the LTA/LTB/TNFalpha locus and Sjogren syndrome.
Title: Association between genetic variants in the tumour necrosis factor/lymphotoxin α/lymphotoxin β locus and primary Sjogren's syndrome in Scandinavian samples.
Data show differential expression of interferon-gamma, TNFSF3, TNFSF10, TNFSF12 and PDGFbeta in CD8+, CD14+ and CD4+ cells.
Title: Gene expression profile of cytokines in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with reduced conditioning.
Findings provide evidence of additional complexity in the transcriptional regulation of LTB with implications for coordinate expression of genes in this important genomic locus.
Title: Transcriptional repression and DNA looping associated with a novel regulatory element in the final exon of the lymphotoxin-β gene.
Soluble LTalphabeta in synovial fluid is associated with a proinflammatory cytokine milieu that contributes to synovitis in rheumatoid arthritis.
Title: Lymphotoxin-alphabeta heterotrimers are cleaved by metalloproteinases and contribute to synovitis in rheumatoid arthritis.
Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and genetic testing. (HuGE Navigator)
Title: Integrative predictive model of coronary artery calcification in atherosclerosis.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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

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
Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat upregulates the expression of lymphotoxin beta (TNF superfamily, member 3, LTB) gene in mammary epithelial cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:480877

RH75844 (e-PCR)
- UniSTS:89779

NoName (e-PCR)
- UniSTS:483258

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	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 cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in immune response	IEA Inferred from Electronic Annotation more info
involved_in lymph node development	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	PubMed
involved_in positive regulation of extrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of interleukin-12 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in skin development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cellular_component	ND No biological Data available more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: lymphotoxin-beta

Names: LT-beta; TNF superfamily member 3; TNF-C; lymphotoxin beta (TNF superfamily, member 3); tumor necrosis factor C; tumor necrosis factor ligand 1C; tumor necrosis factor ligand superfamily member 3

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.

mRNA and Protein(s)

NM_002341.2 → NP_002332.1 lymphotoxin-beta isoform a

See identical proteins and their annotated locations for NP_002332.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript, encodes the longer isoform (a), and can form the heterotrimeric complex with lymphotoxin-alpha.

Source sequence(s)

AL662801

Consensus CDS

CCDS4703.1

UniProtKB/Swiss-Prot

P78370, Q06643, Q52LU8, Q99761

UniProtKB/TrEMBL

A8MQV6, Q5STB2

Related

ENSP00000410481.3, ENST00000429299.3

Conserved Domains (1) summary

pfam00229
Location:102 → 243

TNF; TNF(tumor Necrosis Factor) family
NM_009588.1 → NP_033666.1 lymphotoxin-beta isoform b

See identical proteins and their annotated locations for NP_033666.1

Status: REVIEWED

Description

Transcript Variant: This splice variant (2) lacks an exon in the coding region, compared to variant 1. The encoded protein (isoform b) has a premature stop codon and lacks the majority of the extracellular domain, compared to isoform a. This loss impairs its ability to complex with lympytoxin-alpha.

Source sequence(s)

U89922

Consensus CDS

CCDS4704.1

UniProtKB/Swiss-Prot

Q06643

Related

ENSP00000416113.2, ENST00000446745.2