TNFRSF14 TNF receptor superfamily member 14 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TNFRSF14provided by HGNC
Official Full Name: TNF receptor superfamily member 14provided by HGNC
Primary source: HGNC:HGNC:11912
See related: Ensembl:ENSG00000157873 MIM:602746; AllianceGenome:HGNC:11912
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: TR2; ATAR; HVEA; HVEM; CD270; LIGHTR
Summary: This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Expression: Ubiquitous expression in spleen (RPKM 22.9), duodenum (RPKM 21.7) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.32

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (2554234..2563829)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (1997007..2005473)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (2487810..2495268)

Chromosome 1 - NC_000001.11 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: 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?

The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.
Title: The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.
Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis.
Title: Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis.
MIF promotes Th17 cell differentiation in Hashimoto's thyroiditis by binding HVEM and activating NF-kappaB signaling pathway.
Title: MIF promotes Th17 cell differentiation in Hashimoto's thyroiditis by binding HVEM and activating NF-κB signaling pathway.
Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1[-] stem cell-like T cells over PD-1[+] T cells curbing tumor progression.
Title: Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression.
Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2.
Title: Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2.
BTLA inhibition has a dominant role in the cis-complex of BTLA and HVEM.
Title: BTLA inhibition has a dominant role in the cis-complex of BTLA and HVEM.
The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases.
Title: The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases.
Clinical Significance of BTLA and HVEM Expression on Circulating CD4(+) T and CD8(+) T Cells in Chronic Hepatitis B Virus Infection.
Title: Clinical Significance of BTLA and HVEM Expression on Circulating CD4(+) T and CD8(+) T Cells in Chronic Hepatitis B Virus Infection.
HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160.
Title: HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160.
Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.
Title: Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.

Submit: New GeneRIF Correction See all GeneRIFs (97)

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
Common variants at CD40 and other loci confer risk of rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study. 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
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of tumor necrosis factor receptor superfamily, member 14 (TNFRSF14) in human B cells	PubMed
Vif	vif	HIV-1 Vif downregulates the expression of tumor necrosis factor receptor superfamily, member 14 (TNFRSF14) in Vif-expression T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-74065 (e-PCR)
- UniSTS:5687

STS-U70321 (e-PCR)
- UniSTS:25663

D1S1782E (e-PCR)
- UniSTS:150597

RH79192 (e-PCR)
- UniSTS:18036

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables tumor necrosis factor receptor activity	TAS Traceable Author Statement more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables virus receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in T cell costimulation	IDA Inferred from Direct Assay more info	PubMed
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in defense response to Gram-negative bacterium	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to Gram-positive bacterium	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of adaptive immune memory response	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of alpha-beta T cell proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of T cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cytokine production involved in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in symbiont entry into host cell	IEA Inferred from Electronic Annotation more info
involved_in tumor necrosis factor-mediated signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tumor necrosis factor receptor superfamily member 14

Names: CD40-like protein; herpes virus entry mediator A; tumor necrosis factor receptor superfamily, member 14 (herpesvirus entry mediator); tumor necrosis factor receptor-like gene2

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_047096.1 RefSeqGene

Range

5007..12465

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001297605.2 → NP_001284534.1 tumor necrosis factor receptor superfamily member 14 isoform 2 precursor

Status: REVIEWED

Description

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

Source sequence(s)

BX343044, CD366981, DC383433

UniProtKB/TrEMBL

F6UPZ7

Conserved Domains (1) summary

cd10582
Location:42 → 142

TNFRSF14; Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM)
NM_003820.4 → NP_003811.2 tumor necrosis factor receptor superfamily member 14 isoform 1 precursor

See identical proteins and their annotated locations for NP_003811.2

Status: REVIEWED

Description

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

Source sequence(s)

CD366981, DC383433, U70321

Consensus CDS

CCDS44046.1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4

Related

ENSP00000347948.4, ENST00000355716.5

Conserved Domains (3) summary

cd00185
Location:138 → 186

TNFRSF; CRD2 [structural motif]

cd10582
Location:42 → 142

TNFRSF14; Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM)

cl22855
Location:98 → 196

TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

2554234..2563829

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047433419.1 → XP_047289375.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_047433418.1 → XP_047289374.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_047433414.1 → XP_047289370.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_047433412.1 → XP_047289368.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4

Related

ENSP00000399292.2, ENST00000435221.6
XM_047433416.1 → XP_047289372.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4

Related

ENSP00000399533.1, ENST00000451778.5
XM_047433413.1 → XP_047289369.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4

Related

ENSP00000415254.1, ENST00000434817.5
XM_047433422.1 → XP_047289378.1 tumor necrosis factor receptor superfamily member 14 isoform X4

UniProtKB/TrEMBL

B9A034, F6UPZ7

Related

ENSP00000386859.1, ENST00000409119.5
XM_006711019.3 → XP_006711082.1 tumor necrosis factor receptor superfamily member 14 isoform X3

See identical proteins and their annotated locations for XP_006711082.1

UniProtKB/TrEMBL

F6UPZ7

Conserved Domains (1) summary

cd10582
Location:42 → 142

TNFRSF14; Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM)
XM_047433421.1 → XP_047289377.1 tumor necrosis factor receptor superfamily member 14 isoform X4

UniProtKB/TrEMBL

B9A034, F6UPZ7

Related

ENSP00000411854.1, ENST00000426449.5
XM_047433423.1 → XP_047289379.1 tumor necrosis factor receptor superfamily member 14 isoform X5

UniProtKB/TrEMBL

B4DU65, E9PHP3
XM_011542383.3 → XP_011540685.1 tumor necrosis factor receptor superfamily member 14 isoform X2

See identical proteins and their annotated locations for XP_011540685.1

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

NT_187515.1 Reference GRCh38.p14 ALT_REF_LOCI_1

Range

106553..115019

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054328613.1 → XP_054184588.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054328611.1 → XP_054184586.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054328610.1 → XP_054184585.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054328618.1 → XP_054184593.1 tumor necrosis factor receptor superfamily member 14 isoform X4

UniProtKB/TrEMBL

B9A034, F6UPZ7
XM_054328612.1 → XP_054184587.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054328614.1 → XP_054184589.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054328616.1 → XP_054184591.1 tumor necrosis factor receptor superfamily member 14 isoform X3

UniProtKB/TrEMBL

F6UPZ7
XM_054328617.1 → XP_054184592.1 tumor necrosis factor receptor superfamily member 14 isoform X4

UniProtKB/TrEMBL

B9A034, F6UPZ7
XM_054328619.1 → XP_054184594.1 tumor necrosis factor receptor superfamily member 14 isoform X5

UniProtKB/TrEMBL

B4DU65, E9PHP3
XM_054328609.1 → XP_054184584.1 tumor necrosis factor receptor superfamily member 14 isoform X7
XM_054328608.1 → XP_054184583.1 tumor necrosis factor receptor superfamily member 14 isoform X6
XM_054328615.1 → XP_054184590.1 tumor necrosis factor receptor superfamily member 14 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

1997007..2005473

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054339412.1 → XP_054195387.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054339410.1 → XP_054195385.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054339409.1 → XP_054195384.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054339417.1 → XP_054195392.1 tumor necrosis factor receptor superfamily member 14 isoform X4

UniProtKB/TrEMBL

B9A034, F6UPZ7
XM_054339411.1 → XP_054195386.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054339413.1 → XP_054195388.1 tumor necrosis factor receptor superfamily member 14 isoform X1

UniProtKB/Swiss-Prot

B3KW30, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q92956, Q96J31, Q9UM65

UniProtKB/TrEMBL

F6Q0M4
XM_054339415.1 → XP_054195390.1 tumor necrosis factor receptor superfamily member 14 isoform X3

UniProtKB/TrEMBL

F6UPZ7
XM_054339416.1 → XP_054195391.1 tumor necrosis factor receptor superfamily member 14 isoform X4

UniProtKB/TrEMBL

B9A034, F6UPZ7
XM_054339418.1 → XP_054195393.1 tumor necrosis factor receptor superfamily member 14 isoform X5

UniProtKB/TrEMBL

B4DU65, E9PHP3
XM_054339408.1 → XP_054195383.1 tumor necrosis factor receptor superfamily member 14 isoform X9
XM_054339407.1 → XP_054195382.1 tumor necrosis factor receptor superfamily member 14 isoform X8
XM_054339414.1 → XP_054195389.1 tumor necrosis factor receptor superfamily member 14 isoform X2