The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediat... See more...

Aliases for TNFRSF10A Gene

Aliases for TNFRSF10A Gene

  • TNF Receptor Superfamily Member 10a 2 3 5
  • TRAILR1 2 3 4
  • DR4 2 3 4
  • Tumor Necrosis Factor Receptor Superfamily, Member 10a 2 3
  • Tumor Necrosis Factor Receptor Superfamily Member 10A 3 4
  • TNF-Related Apoptosis-Inducing Ligand Receptor 1 3 4
  • TRAIL Receptor 1 3 4
  • Death Receptor 4 3 4
  • TRAILR-1 2 3
  • TRAIL-R1 3 4
  • CD261 2 3
  • APO2 3 4
  • Tumor Necrosis Factor Receptor Superfamily Member 10a Variant 2 3
  • Cytotoxic TRAIL Receptor 3
  • CD261 Antigen 4
  • TNFRSF10A 5
  • Apo2 2

External Ids for TNFRSF10A Gene

Previous GeneCards Identifiers for TNFRSF10A Gene

  • GC08M022787
  • GC08M023403
  • GC08M023070
  • GC08M023104
  • GC08M023048
  • GC08M021594

Summaries for TNFRSF10A Gene

Entrez Gene Summary for TNFRSF10A Gene

  • The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [provided by RefSeq, Jul 2008]

GeneCards Summary for TNFRSF10A Gene

TNFRSF10A (TNF Receptor Superfamily Member 10a) is a Protein Coding gene. Diseases associated with TNFRSF10A include Hirata Disease and Temporal Arteritis. Among its related pathways are Apoptosis Modulation and Signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include transcription factor binding and protease binding. An important paralog of this gene is TNFRSF10B.

UniProtKB/Swiss-Prot Summary for TNFRSF10A Gene

  • Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:26457518). The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis (PubMed:19090789). Promotes the activation of NF-kappa-B (PubMed:9430227).

Gene Wiki entry for TNFRSF10A Gene

Additional gene information for TNFRSF10A Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TNFRSF10A Gene

Genomics for TNFRSF10A Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TNFRSF10A Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNFRSF10A on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TNFRSF10A

Top Transcription factor binding sites by QIAGEN in the TNFRSF10A gene promoter:
  • ATF-2
  • c-Jun
  • MyoD
  • Sp1
  • STAT1
  • STAT1alpha

Genomic Locations for TNFRSF10A Gene

Genomic Locations for TNFRSF10A Gene
chr8:23,190,452-23,225,102
(GRCh38/hg38)
Size:
34,651 bases
Orientation:
Minus strand
chr8:23,047,965-23,082,680
(GRCh37/hg19)
Size:
34,716 bases
Orientation:
Minus strand

Genomic View for TNFRSF10A Gene

Genes around TNFRSF10A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNFRSF10A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNFRSF10A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNFRSF10A Gene

Proteins for TNFRSF10A Gene

  • Protein details for TNFRSF10A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00220-TR10A_HUMAN
    Recommended name:
    Tumor necrosis factor receptor superfamily member 10A
    Protein Accession:
    O00220
    Secondary Accessions:
    • A8K5I4
    • Q53Y72
    • Q96E62

    Protein attributes for TNFRSF10A Gene

    Size:
    468 amino acids
    Molecular mass:
    50089 Da
    Quaternary structure:
    • Monomer (PubMed:26457518). Homooligomers and heterooligomers with TNFRSF10B (PubMed:19090789). Three TNFRSF10A molecules interact with the TNFSF10 homotrimer (PubMed:26457518). Can interact with TRADD and RIPK1. Interacts with ARAP1. In the absence of stimulation, interacts with BIRC2, DDX3X and GSK3B. The interaction with BIRC2 and DDX3X is further enhanced upon receptor stimulation and accompanied by DDX3X and BIRC2 cleavage (PubMed:18846110). Interacts with ZDHHC3 (PubMed:22240897).
    • (Microbial infection) Interacts with HCMV protein UL141; this interaction prevents TNFRSF10A cell surface expression.

    Three dimensional structures from OCA and Proteopedia for TNFRSF10A Gene

neXtProt entry for TNFRSF10A Gene

Post-translational modifications for TNFRSF10A Gene

  • Palmitoylated (PubMed:19090789). Palmitoylation of TNFRSF10A is required for its association with lipid rafts, oligomerization and function in TRAIL-induced cell death (PubMed:19090789). Palmitoylated by ZDHHC3 (Probable).
  • Glycosylation at Asn156
  • Modification sites at PhosphoSitePlus

Other Protein References for TNFRSF10A Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for TNFRSF10A

No data available for DME Specific Peptides for TNFRSF10A Gene

Domains & Families for TNFRSF10A Gene

Gene Families for TNFRSF10A Gene

Protein Domains for TNFRSF10A Gene

InterPro:
Blocks:
  • TNFR/CD27/30/40/95 cysteine-rich region
  • Death domain
ProtoNet:

Suggested Antigen Peptide Sequences for TNFRSF10A Gene

GenScript: Design optimal peptide antigens:
  • Tumor necrosis factor receptor superfamily member 10a (C1K3N4_HUMAN)
  • Tumor necrosis factor receptor superfamily member 10a variant 2 (F8U8C0_HUMAN)
  • TNF-related apoptosis-inducing ligand receptor 1 (TR10A_HUMAN)
genes like me logo Genes that share domains with TNFRSF10A: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TNFRSF10A Gene

Function for TNFRSF10A Gene

Molecular function for TNFRSF10A Gene

UniProtKB/Swiss-Prot Function:
Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:26457518). The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis (PubMed:19090789). Promotes the activation of NF-kappa-B (PubMed:9430227).
GENATLAS Biochemistry:
tumor necrosis factor receptor superfamily,member 10A,widely expressed,TNF related,widely expressed,apoptosis induced ligand (TRAIL) receptor 1,TP53 inducible,binding APO2L,inducing a caspase-dependent apoptotic pathway,FADD independent

Phenotypes From GWAS Catalog for TNFRSF10A Gene

Gene Ontology (GO) - Molecular Function for TNFRSF10A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 21785459
GO:0005035 death receptor activity TAS 9082980
GO:0005515 protein binding IEA,IPI 17047155
GO:0008134 transcription factor binding IPI 18165900
GO:0038023 signaling receptor activity NAS 9311998
genes like me logo Genes that share ontologies with TNFRSF10A: view
genes like me logo Genes that share phenotypes with TNFRSF10A: view

Animal Models for TNFRSF10A Gene

MGI Knock Outs for TNFRSF10A:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNFRSF10A

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TNFRSF10A Gene

Localization for TNFRSF10A Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNFRSF10A Gene

Cell membrane. Single-pass type I membrane protein. Membrane raft. Cytoplasm, cytosol. Note=Palmitoylation is required for association with membranes. {ECO:0000269 PubMed:22240897}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TNFRSF10A gene
Compartment Confidence
plasma membrane 5
cytosol 5
golgi apparatus 5
extracellular 3
mitochondrion 3
nucleus 3
cytoskeleton 2
endoplasmic reticulum 2
endosome 2
lysosome 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TNFRSF10A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005794 Golgi apparatus IDA 22240897
GO:0005829 cytosol IDA 22240897
GO:0005886 plasma membrane IEA,TAS --
GO:0009986 cell surface IBA,IDA 22952982
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with TNFRSF10A: view

Pathways & Interactions for TNFRSF10A Gene

PathCards logo

SuperPathways for TNFRSF10A Gene

SuperPathway Contained pathways
1 CASP8 activity is inhibited
2 Apoptosis Modulation and Signaling
.35
.31
3 PEDF Induced Signaling
.51
.47
.43
4 TNFR1 Pathway
.42
.40
5 Akt Signaling
.60
.60
.55
genes like me logo Genes that share pathways with TNFRSF10A: view

Pathways by source for TNFRSF10A Gene

2 Sino Biological pathways for TNFRSF10A Gene
1 GeneGo (Thomson Reuters) pathway for TNFRSF10A Gene
  • Apoptosis and survival Apoptotic TNF-family pathways
16 Qiagen pathways for TNFRSF10A Gene
  • Akt Signaling
  • all-trans-Retinoic Acid Mediated Apoptosis
  • Antioxidant Action of Vitamin-C
  • Apoptosis through Death Receptors
  • Cellular Apoptosis Pathway
1 Cell Signaling Technology pathway for TNFRSF10A Gene
1 GeneTex pathway for TNFRSF10A Gene

SIGNOR curated interactions for TNFRSF10A Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for TNFRSF10A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process NAS 9311998
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process TAS --
GO:0007165 signal transduction IEA,TAS 9082980
GO:0007166 cell surface receptor signaling pathway TAS --
GO:0007250 activation of NF-kappaB-inducing kinase activity NAS 9430227
genes like me logo Genes that share ontologies with TNFRSF10A: view

Drugs & Compounds for TNFRSF10A Gene

(31) Drugs for TNFRSF10A Gene - From: PharmGKB, DGIdb, IUPHAR, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
dulanermin Investigational Pharma antibody, agonist Therapeutic Antibodies, TNF related apoptosis inducing ligand (TRAIL) receptor agonists 0
TRAIL Pharma 0
Tumor necrosis factor alpha (TNF-alpha) inhibitors Pharma 0
mapatumumab Pharma antibody, Agonist Therapeutic Antibodies, TNF related apoptosis inducing ligand (TRAIL) receptor agonists 7

(17) Additional Compounds for TNFRSF10A Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TNFRSF10A: view

Transcripts for TNFRSF10A Gene

mRNA/cDNA for TNFRSF10A Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNFRSF10A

Alternative Splicing Database (ASD) splice patterns (SP) for TNFRSF10A Gene

No ASD Table

Relevant External Links for TNFRSF10A Gene

GeneLoc Exon Structure for
TNFRSF10A

Expression for TNFRSF10A Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TNFRSF10A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TNFRSF10A Gene

This gene is overexpressed in Liver (46.3) and Breast (17.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TNFRSF10A Gene



Protein tissue co-expression partners for TNFRSF10A Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TNFRSF10A

SOURCE GeneReport for Unigene cluster for TNFRSF10A Gene:

Hs.591834

mRNA Expression by UniProt/SwissProt for TNFRSF10A Gene:

O00220-TR10A_HUMAN
Tissue specificity: Widely expressed. High levels are found in spleen, peripheral blood leukocytes, small intestine and thymus, but also in K-562 erythroleukemia cells, MCF-7 breast carcinoma cells and activated T-cells.

Evidence on tissue expression from TISSUES for TNFRSF10A Gene

  • Blood(3.1)
  • Liver(3)
  • Spleen(2.9)
  • Intestine(2.9)
  • Lymph node(2.8)
  • Kidney(2.8)
  • Lung(2.7)
  • Bone marrow(2.6)
  • Pancreas(2.5)
  • Thyroid gland(2.5)
  • Skin(2.5)
  • Heart(2.5)
  • Nervous system(2.4)
  • Muscle(2.4)
  • Stomach(2.2)
genes like me logo Genes that share expression patterns with TNFRSF10A: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for TNFRSF10A Gene

Orthologs for TNFRSF10A Gene

This gene was present in the common ancestor of chordates.

Orthologs for TNFRSF10A Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TNFRSF10A 30 31
  • 99 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TNFRSF10D 30 31
  • 65.45 (n)
ManyToMany
-- 31
  • 48 (a)
ManyToMany
-- 31
  • 42 (a)
ManyToMany
Rat
(Rattus norvegicus)
Mammalia Tnfrsf10b 30
  • 62.09 (n)
Mouse
(Mus musculus)
Mammalia Tnfrsf10b 30 17 31
  • 55.84 (n)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 31 (a)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 24 (a)
OneToMany
Chicken
(Gallus gallus)
Aves TVB 31
  • 26 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 25 (a)
OneToMany
Zebrafish
(Danio rerio)
Actinopterygii hdr 31
  • 19 (a)
ManyToMany
tnfrsfa 31
  • 17 (a)
ManyToMany
Species where no ortholog for TNFRSF10A was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TNFRSF10A Gene

ENSEMBL:
Gene Tree for TNFRSF10A (if available)
TreeFam:
Gene Tree for TNFRSF10A (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TNFRSF10A: view image

Paralogs for TNFRSF10A Gene

(3) SIMAP similar genes for TNFRSF10A Gene using alignment to 5 proteins:

  • TR10A_HUMAN
  • C1K3N4_HUMAN
  • E5RFH1_HUMAN
  • F8U8C0_HUMAN
  • L8EA63_HUMAN
genes like me logo Genes that share paralogs with TNFRSF10A: view

Variants for TNFRSF10A Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TNFRSF10A Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
712472 Benign: not provided 23,199,389(-) G/A SYNONYMOUS_VARIANT
715933 Likely Benign: not provided 23,202,700(-) G/T SYNONYMOUS_VARIANT
729940 Benign: not provided 23,197,122(-) A/C INTRON_VARIANT
729941 Benign: not provided 23,199,391(-) T/G MISSENSE_VARIANT
730510 Benign: not provided 23,224,856(-) C/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for TNFRSF10A Gene

Structural Variations from Database of Genomic Variants (DGV) for TNFRSF10A Gene

Variant ID Type Subtype PubMed ID
esv2736750 CNV deletion 23290073
esv2759604 CNV loss 17122850
esv3616630 CNV gain 21293372
nsv1017570 CNV gain 25217958
nsv1027718 CNV gain 25217958
nsv1068323 OTHER inversion 25765185
nsv610777 CNV loss 21841781
nsv951114 CNV deletion 24416366
nsv981919 CNV duplication 23825009

Variation tolerance for TNFRSF10A Gene

Residual Variation Intolerance Score: 83% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.20; 62.02% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TNFRSF10A Gene

Human Gene Mutation Database (HGMD)
TNFRSF10A
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TNFRSF10A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TNFRSF10A Gene

Disorders for TNFRSF10A Gene

MalaCards: The human disease database

(50) MalaCards diseases for TNFRSF10A Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hirata disease
  • insulin autoimmune syndrome
temporal arteritis
  • giant cell arteritis; gca
chondromalacia
pemphigoid gestationis
  • gestational herpes
pharyngoconjunctival fever
  • adenoviral pharyngoconjunctivitis
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TNFRSF10A

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TNFRSF10A: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TNFRSF10A Gene

Publications for TNFRSF10A Gene

  1. The receptor for the cytotoxic ligand TRAIL. (PMID: 9082980) Pan G … Dixit VM (Science (New York, N.Y.) 1997) 2 3 4 23
  2. TRAIL-R1 polymorphisms and cancer susceptibility: an evidence-based meta-analysis. (PMID: 19643596) Chen B … Wu JQ (European journal of cancer (Oxford, England : 1990) 2009) 3 23 41
  3. Ala228 variant of trail receptor 1 affecting the ligand binding site is associated with chronic lymphocytic leukemia, mantle cell lymphoma, prostate cancer, head and neck squamous cell carcinoma and bladder cancer. (PMID: 16217763) Wolf S … Lichter P (International journal of cancer 2006) 3 23 41
  4. Death receptor 4 variants and colorectal cancer risk. (PMID: 17035413) Frank B … Burwinkel B (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2006) 3 23 41
  5. A single nucleotide polymorphism in the extracellular domain of TRAIL receptor DR4 at nucleotide 626 in gastric cancer patients in Japan. (PMID: 16012731) Kuraoka K … Yasui W (Oncology reports 2005) 3 23 41

Products for TNFRSF10A Gene

Sources for TNFRSF10A Gene