TNFRSF1A TNF receptor superfamily member 1A [Homo sapiens (human)] - Gene

Summary

Official Symbol: TNFRSF1Aprovided by HGNC
Official Full Name: TNF receptor superfamily member 1Aprovided by HGNC
Primary source: HGNC:HGNC:11916
See related: Ensembl:ENSG00000067182 MIM:191190; AllianceGenome:HGNC:11916
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: FPF; p55; p60; TBP1; TNF-R; TNFAR; TNFR1; p55-R; CD120a; TNFR55; TNFR60; TNF-R-I; TNF-R55
Summary: This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]
Expression: Ubiquitous expression in small intestine (RPKM 52.0), gall bladder (RPKM 48.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12p13.31

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (6328771..6342076, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (6338163..6351461, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (6437937..6451242, complement)

Chromosome 12 - NC_000012.12 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: 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?

TNFR1 signaling promotes pancreatic tumor growth by limiting dendritic cell number and function.
Title: TNFR1 signaling promotes pancreatic tumor growth by limiting dendritic cell number and function.
Association of polymorphisms in the TNFA, TNFRSF1A and TNFRSF1B genes with lepromatous leprosy in Western Mexican patients.
Title: Association of polymorphisms in the TNFA, TNFRSF1A and TNFRSF1B genes with lepromatous leprosy in Western Mexican patients.
Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.
Title: Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.
Progesterone modulates TNF receptors expression by Jurkat cells cultured with plasma from pregnant women with preeclampsia.
Title: Progesterone modulates TNF receptors expression by Jurkat cells cultured with plasma from pregnant women with preeclampsia.
Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma.
Title: Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma.
TNFRSF1A-pR92Q variant identifies a subset of patients more similar to systemic undifferentiated recurrent fever than TNF receptor-associated periodic syndrome.
Title: TNFRSF1A-pR92Q variant identifies a subset of patients more similar to systemic undifferentiated recurrent fever than TNF receptor-associated periodic syndrome.
A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature.
Title: A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature.
TNFR-1 and GDF-15 Are Associated With Plasma Neurofilament Light Chain and Progranulin Among Community-Dwelling Older Adults: A Secondary Analysis of the MAPT Study.
Title: TNFR-1 and GDF-15 Are Associated With Plasma Neurofilament Light Chain and Progranulin Among Community-Dwelling Older Adults: A Secondary Analysis of the MAPT Study.
C-Reactive Protein, Interleukin-6, Trimethylamine-N-Oxide, Syndecan-1, Nitric Oxide, and Tumor Necrosis Factor Receptor-1 in Heart Failure with Preserved Versus Reduced Ejection Fraction: a Meta-Analysis.
Title: C-Reactive Protein, Interleukin-6, Trimethylamine-N-Oxide, Syndecan-1, Nitric Oxide, and Tumor Necrosis Factor Receptor-1 in Heart Failure with Preserved Versus Reduced Ejection Fraction: a Meta-Analysis.
Impact of Tumor Necrosis Factor Receptor 1 (TNFR1) Polymorphism on Dry Eye Disease.
Title: Impact of Tumor Necrosis Factor Receptor 1 (TNFR1) Polymorphism on Dry Eye Disease.

Submit: New GeneRIF Correction See all GeneRIFs (520)

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
Multiple sclerosis, susceptibility to, 5 MedGen: C3553728 OMIM: 614810 GeneReviews: Not available	not available
TNF receptor-associated periodic fever syndrome (TRAPS) MedGen: C1275126 OMIM: 142680 GeneReviews: TNF Receptor-Associated Periodic Fever Syndrome	not available

EBI GWAS Catalog

Description
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. 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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Replication interactions

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of TNFRSF1A	PubMed
HIV-1 infected clinical samples have plasma extracellular vesicles that contain elevated CCL1 (I309), IGFBP1, CCL5 (RANTES), GMCSF, ANG, ADIPOQ (ACRP30), CSF3 (GCSF), CXCL1 (GRO), ICAM1, IL2RA, IL6R, TNFRSF1A, and TIMP1 when compared to healthy donors	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 Nef downregulates the cell surface expression of tumor necrosis factor receptor superfamily, member 1A (CD120a)	PubMed
Tat	tat	HIV-1 Tat upregulates the expression of tumor necrosis factor receptor superfamily, member 1A gene (TNFRSF1A; TNFR1) in mammary epithelial cells	PubMed
	tat	HIV-1 Tat protects tumor necrosis factor receptor p55 from TNF-alpha-induced repression and amplifies TNF-alpha activity in stably tat-transfected HeLa cells	PubMed
capsid	gag	Herpes simplex virus type 2-Infected monocyte-derived dendritic cells (MDDCs) produce TNF-alpha, which binds to its receptor TNF-R1 and upregulates the expression of CCR5 on cell surface, leading to enhance HIV-1 p24 release from MDDCs	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

GDB:214852 (e-PCR)
- UniSTS:156197

D8S2279 (e-PCR)
- UniSTS:473907

RH75052 (e-PCR)
- UniSTS:91966

D12S356 (e-PCR), detects polymorphism
- UniSTS:39007

WI-18755 (e-PCR)
- UniSTS:57193

STS-M58286 (e-PCR)
- UniSTS:34937

D12S889 (e-PCR)
- UniSTS:149919

GDB:384764 (e-PCR)
- UniSTS:157097

G15949 (e-PCR)
- UniSTS:44467

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables tumor necrosis factor binding	IBA Inferred from Biological aspect of Ancestor more info
enables tumor necrosis factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables tumor necrosis factor receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables tumor necrosis factor receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables tumor necrosis factor receptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in aortic valve development	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell surface receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cytokine-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in defense response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in extrinsic apoptotic signaling pathway via death domain receptors	TAS Traceable Author Statement more info	PubMed
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in intrinsic apoptotic signaling pathway in response to DNA damage	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cardiac muscle hypertrophy	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of extracellular matrix constituent secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of amide metabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process involved in morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of execution phase of apoptosis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in prostaglandin metabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pulmonary valve development	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of establishment of endothelial barrier	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of membrane lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of tumor necrosis factor-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in tumor necrosis factor-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in tumor necrosis factor-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tumor necrosis factor-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in tumor necrosis factor-mediated signaling pathway	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in membrane raft	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of tumor necrosis factor receptor superfamily complex	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: tumor necrosis factor receptor superfamily member 1A

Names: TNF-R1; TNF-RI; TNFR-I; tumor necrosis factor binding protein 1; tumor necrosis factor receptor type 1; tumor necrosis factor-alpha receptor

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_007506.1 RefSeqGene

Range

4979..18339

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_193

mRNA and Protein(s)

NM_001065.4 → NP_001056.1 tumor necrosis factor receptor superfamily member 1A isoform 1 precursor

See identical proteins and their annotated locations for NP_001056.1

Status: REVIEWED

Description

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

Source sequence(s)

AK315509, BC010140, M63121

Consensus CDS

CCDS8542.1

UniProtKB/Swiss-Prot

A8K4X3, B2RDE4, B3KPQ1, B4DQB7, B4E309, B5M0B5, D3DUR1, P19438, Q9UCA4

UniProtKB/TrEMBL

F5H061

Related

ENSP00000162749.2, ENST00000162749.7

Conserved Domains (3) summary

cd08313
Location:358 → 438

Death_TNFR1; Death domain of Tumor Necrosis Factor Receptor 1

cd10576
Location:44 → 175

TNFRSF1A; Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1

cl26464
Location:250 → 366

Atrophin-1; Atrophin-1 family
NM_001346091.2 → NP_001333020.1 tumor necrosis factor receptor superfamily member 1A isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start site compared to variant 1. The encoded isoform (2) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1.

Source sequence(s)

BC010140, JN172914

UniProtKB/TrEMBL

F5H061, J9PH39
NM_001346092.2 → NP_001333021.1 tumor necrosis factor receptor superfamily member 1A isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate translation start site compared to variant 1. The encoded isoform (3) has a shorter and distinct N-terminus and lacks a predicted signal peptide compared to isoform 1.

Source sequence(s)

AC006057, BC010140, KF455591

UniProtKB/Swiss-Prot

P19438

RNA

NR_144351.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC006057, BC010140, KF455591

Related

ENST00000698340.1