LTA (Lymphotoxin-A)

2005-02-01   Fei Chen 

Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd, Morgantown, WV 26505, USA

Identity

HGNC
LOCATION
6p21.33
LOCUSID
ALIAS
LT,TNFB,TNFSF1,TNLG1E

DNA/RNA

Description

The human TNFb gene is located next to HLA-C and HLA-B loci in chromosome 6 (6p21.3). The gene spans 2005bp with 4 exons, which transcribes a TNFb mRNA with size of 1386nt.

Proteins

Atlas Image

Description

The human TNFb protein contains 205 amino acids. The soluble form of TNFb is usually a homotrimer with a relative molecular mass of 60 to 70 kDa, whereas the membrane form of TNFb is a heteromeric complex with lymphotoxin b (TNFc, LTb, TNFSF3). The human TNFb shares 35% identity and 50% homology in amino acid sequence with the human TNFa. The biological function of TNFb is mediated largely by TNFa receptor 1 and TNFa receptor 2. Recent studies suggested that TNFb can also recognize LIGHT ( TNFSF14) receptor.

Expression

The main cellular source of TNFb is the activated lymphocytes in immune response.

Localisation

Cell membrane, extracellular soluble form, blood stream, and biological fluids.

Function

The human TNFb is an important cytokine involved in the development of secondary lymphoid organs and inflammatory responses.

Implicated in

Disease
The polymorphism of TNFb gene in either the coding region or the promoter region has been associated with Crohn disease and myocardial infarction.

Bibliography

Pubmed IDLast YearTitleAuthors
129494982003Signalling pathways of the TNF superfamily: a double-edged sword.Aggarwal BB et al
129744792003Lymphotoxin/light, lymphoid microenvironments and autoimmune disease.Gommerman JL et al

Other Information

Locus ID:

NCBI: 4049
MIM: 153440
HGNC: 6709
Ensembl: ENSG00000226979

Variants:

dbSNP: 4049
ClinVar: 4049
TCGA: ENSG00000226979
COSMIC: LTA

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000226979ENST00000418386P01374
ENSG00000226979ENST00000418386Q5STV3
ENSG00000226979ENST00000454783P01374
ENSG00000226979ENST00000454783Q5STV3

Expression (GTEx)

0
50
100
150
200
250
300
350

Pathways

PathwaySourceExternal ID
Cytokine-cytokine receptor interactionKEGGko04060
Type I diabetes mellitusKEGGko04940
Cytokine-cytokine receptor interactionKEGGhsa04060
Type I diabetes mellitusKEGGhsa04940
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
NF-kappa B signaling pathwayKEGGhsa04064
NF-kappa B signaling pathwayKEGGko04064
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
TNFR2 non-canonical NF-kB pathwayREACTOMER-HSA-5668541
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathwayREACTOMER-HSA-5676594
TNFs bind their physiological receptorsREACTOMER-HSA-5669034

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA443936Drug HypersensitivityDiseaseClinicalAnnotationassociatedPD
PA444546HypersensitivityDiseaseClinicalAnnotationassociatedPD11294926
PA448004abacavirChemicalClinicalAnnotationassociatedPD
PA448785carbamazepineChemicalClinicalAnnotationassociatedPD11294926

References

Pubmed IDYearTitleCitations
124265692002Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.173
124265692002Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.173
198005752009A lymphotoxin-driven pathway to hepatocellular carcinoma.138
163891812006Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium.137
177034122007Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.100
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
200479772010Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium.64
170186372006Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma.61
170186372006Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma.61
167751702006Inflammation-related gene polymorphisms and colorectal adenoma.57

Citation

Fei Chen

LTA (Lymphotoxin-A)

Atlas Genet Cytogenet Oncol Haematol. 2005-02-01

Online version: http://atlasgeneticsoncology.org/gene/41209/lta