TNF
tumor necrosis factor, the group of Tumor necrosis factor superfamily
Basic information
Region (hg38): 6:31575564-31578336
Previous symbols: [ "TNFA" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (6 variants)
- Inborn genetic diseases (2 variants)
- Migraine with or without aura, susceptibility to, 1 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNF gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 4 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 3 | 4 | 2 |
Variants in TNF
This is a list of pathogenic ClinVar variants found in the TNF region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-31575758-T-A | Migraine with or without aura, susceptibility to, 1 | Uncertain significance (Jul 19, 2022) | ||
| 6-31575780-C-A | Likely benign (Jul 29, 2018) | |||
| 6-31575828-G-T | Benign (Aug 18, 2018) | |||
| 6-31575862-G-T | not specified | Uncertain significance (Jul 13, 2022) | ||
| 6-31576785-C-T | Benign/Likely benign (Feb 01, 2024) | |||
| 6-31577155-G-T | not specified | Uncertain significance (Nov 28, 2023) | ||
| 6-31577157-C-T | TNF receptor binding, altered | Pathogenic (Jan 21, 1993) | ||
| 6-31577185-T-C | not specified | Uncertain significance (Jan 31, 2023) | ||
| 6-31577189-G-A | Likely benign (May 24, 2018) | |||
| 6-31577312-C-T | Likely benign (Jun 28, 2018) | |||
| 6-31577324-C-T | Likely benign (Aug 06, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TNF | protein_coding | protein_coding | ENST00000449264 | 4 | 2770 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.803 | 0.196 | 123531 | 0 | 2 | 123533 | 0.00000809 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.62 | 84 | 137 | 0.611 | 0.00000799 | 1493 |
| Missense in Polyphen | 9 | 34.644 | 0.25978 | 447 | ||
| Synonymous | 0.845 | 54 | 62.5 | 0.864 | 0.00000378 | 501 |
| Loss of Function | 2.59 | 1 | 9.74 | 0.103 | 5.67e-7 | 98 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000296 | 0.0000296 |
| Ashkenazi Jewish | 0.000100 | 0.000100 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918, PubMed:16829952, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). {ECO:0000250|UniProtKB:P06804, ECO:0000269|PubMed:16829952, ECO:0000269|PubMed:22517918, ECO:0000269|PubMed:23396208}.;
- Disease
- DISEASE: Psoriatic arthritis (PSORAS) [MIM:607507]: An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). {ECO:0000269|PubMed:12746914}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Antigen processing and presentation - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Type I diabetes mellitus - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Pertussis - Homo sapiens (human);Legionellosis - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Graft-versus-host disease - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Influenza A - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Asthma - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Malaria - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Fc Epsilon Receptor I Signaling in Mast Cells;Matrix Metalloproteinases;Regulation of toll-like receptor signaling pathway;Selenium Micronutrient Network;Vitamin B12 Metabolism;MicroRNAs in cardiomyocyte hypertrophy;Type II diabetes mellitus;Folate Metabolism;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Alzheimers Disease;TNF alpha Signaling Pathway;Allograft Rejection;Adipogenesis;Spinal Cord Injury;Amyotrophic lateral sclerosis (ALS);Apoptosis;Polycystic Kidney Disease Pathway;Aryl Hydrocarbon Receptor;EBV LMP1 signaling;Cardiac Hypertrophic Response;Apoptosis-related network due to altered Notch3 in ovarian cancer;Aryl Hydrocarbon Receptor Pathway;Nuclear Receptors Meta-Pathway;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Overview of nanoparticle effects;EV release from cardiac cells and their functional effects;Transcription factor regulation in adipogenesis;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NF-kB survival signaling;Lung fibrosis;Apoptotic Signaling Pathway;MAPK Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;RIG-I-like Receptor Signaling;Development and heterogeneity of the ILC family;Oxidative Damage;Protein alkylation leading to liver fibrosis;NO-cGMP-PKG mediated Neuroprotection;Interleukin-10 signaling;Interleukin-4 and 13 signaling;Fibrin Complement Receptor 3 Signaling Pathway;Cytokines and Inflammatory Response;TGF-beta Receptor Signaling;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Monoamine Transport;Toll-like Receptor Signaling Pathway;TWEAK;Signal Transduction;mechanism of gene regulation by peroxisome proliferators via ppara;visceral fat deposits and the metabolic syndrome;tnfr1 signaling pathway;il-10 anti-inflammatory signaling pathway;cadmium induces dna synthesis and proliferation in macrophages;hiv-1 nef: negative effector of fas and tnf;signal transduction through il1r;tnf/stress related signaling;nf-kb signaling pathway;nfat and hypertrophy of the heart ;nfkb activation by nontypeable hemophilus influenzae;stress induction of hsp regulation;keratinocyte differentiation;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Immune System;ceramide signaling pathway;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;TNFR1-induced NFkappaB signaling pathway;TNFR1-induced proapoptotic signaling;TNFR1-mediated ceramide production;TNF signaling;sodd/tnfr1 signaling pathway;JAK STAT pathway and regulation;Death Receptor Signalling;Regulation of TNFR1 signaling;RXR and RAR heterodimerization with other nuclear receptor;Angiopoietin receptor Tie2-mediated signaling;GPCR signaling-G alpha i;TNFalpha;TNF;Canonical NF-kappaB pathway;Caspase Cascade in Apoptosis;IL23-mediated signaling events;HIV-1 Nef: Negative effector of Fas and TNF-alpha;IL27-mediated signaling events;TNF receptor signaling pathway ;Downstream signaling in naïve CD8+ T cells;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;amb2 Integrin signaling;Signaling events mediated by HDAC Class I;Ceramide signaling pathway;Cellular roles of Anthrax toxin
(Consensus)
Intolerance Scores
- loftool
- 0.194
- rvis_EVS
- -0.03
- rvis_percentile_EVS
- 51.4
Haploinsufficiency Scores
- pHI
- 0.819
- hipred
- N
- hipred_score
- 0.462
- ghis
- 0.585
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tnf
- Phenotype
- immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; embryo phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- tnfb
- Affected structure
- liver
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- obsolete protein import into nucleus, translocation;negative regulation of transcription by RNA polymerase II;MAPK cascade;activation of MAPKKK activity;activation of MAPK activity;microglial cell activation;positive regulation of cytokine production;positive regulation of protein phosphorylation;negative regulation of endothelial cell proliferation;chronic inflammatory response to antigenic stimulus;negative regulation of cytokine secretion involved in immune response;positive regulation of chronic inflammatory response to antigenic stimulus;positive regulation of humoral immune response mediated by circulating immunoglobulin;glucose metabolic process;regulation of transcription by RNA polymerase II;activation of cysteine-type endopeptidase activity involved in apoptotic process;inflammatory response;humoral immune response;I-kappaB kinase/NF-kappaB signaling;JNK cascade;extrinsic apoptotic signaling pathway via death domain receptors;intrinsic apoptotic signaling pathway in response to DNA damage;response to virus;response to salt stress;regulation of signaling receptor activity;positive regulation of gene expression;negative regulation of gene expression;negative regulation of alkaline phosphatase activity;regulation of tumor necrosis factor-mediated signaling pathway;negative regulation of lipid storage;positive regulation of phosphatidylinositol 3-kinase signaling;cytokine-mediated signaling pathway;extracellular matrix organization;osteoclast differentiation;sequestering of triglyceride;cortical actin cytoskeleton organization;positive regulation of protein complex assembly;positive regulation of fever generation;lipopolysaccharide-mediated signaling pathway;negative regulation of interleukin-6 production;positive regulation of chemokine production;positive regulation of interferon-gamma production;positive regulation of interleukin-8 production;receptor biosynthetic process;positive regulation of peptidyl-serine phosphorylation;tumor necrosis factor-mediated signaling pathway;positive regulation of heterotypic cell-cell adhesion;negative regulation of myosin-light-chain-phosphatase activity;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of apoptotic process;positive regulation of programmed cell death;regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of protein complex disassembly;positive regulation of protein complex disassembly;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of MAP kinase activity;protein kinase B signaling;positive regulation of JUN kinase activity;negative regulation of growth of symbiont in host;negative regulation of viral genome replication;positive regulation of chemokine biosynthetic process;positive regulation of interleukin-6 biosynthetic process;positive regulation of interleukin-8 biosynthetic process;positive regulation of nitric oxide biosynthetic process;negative regulation of fat cell differentiation;negative regulation of myoblast differentiation;negative regulation of osteoblast differentiation;positive regulation of osteoclast differentiation;positive regulation of protein catabolic process;positive regulation of cell adhesion;positive regulation of protein kinase activity;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;negative regulation of mitotic cell cycle;positive regulation of transcription by RNA polymerase II;positive regulation of translational initiation by iron;negative regulation of glucose import;positive regulation of JAK-STAT cascade;astrocyte activation;embryonic digestive tract development;positive regulation of smooth muscle cell proliferation;positive regulation of cytokine secretion;positive regulation of inflammatory response;positive regulation of fractalkine biosynthetic process;positive regulation of phagocytosis;negative regulation of neurogenesis;regulation of insulin secretion;positive regulation of synaptic transmission;regulation of synapse organization;defense response to Gram-positive bacterium;cognition;leukocyte tethering or rolling;negative regulation of lipid catabolic process;positive regulation of nitric-oxide synthase activity;regulation of immunoglobulin secretion;positive regulation of membrane protein ectodomain proteolysis;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;positive regulation of protein transport;response to glucocorticoid;positive regulation of hair follicle development;positive regulation of protein kinase B signaling;regulation of synaptic transmission, glutamatergic;positive regulation of glial cell proliferation;positive regulation of vitamin D biosynthetic process;positive regulation of calcidiol 1-monooxygenase activity;epithelial cell proliferation involved in salivary gland morphogenesis;regulation of branching involved in salivary gland morphogenesis;negative regulation of branching involved in lung morphogenesis;positive regulation of ERK1 and ERK2 cascade;positive regulation of calcineurin-NFAT signaling cascade;cellular response to amino acid stimulus;cellular response to nicotine;cellular response to organic cyclic compound;death-inducing signaling complex assembly;positive regulation of mononuclear cell migration;positive regulation of podosome assembly;endothelial cell apoptotic process;protein localization to plasma membrane;positive regulation of chemokine secretion;extrinsic apoptotic signaling pathway;necroptotic signaling pathway;positive regulation of neuroinflammatory response;positive regulation of NIK/NF-kappaB signaling;positive regulation of superoxide dismutase activity;positive regulation of protein localization to plasma membrane;regulation of establishment of endothelial barrier;negative regulation of bicellular tight junction assembly;regulation of microglial cell activation;positive regulation of vascular smooth muscle cell proliferation;positive regulation of leukocyte adhesion to vascular endothelial cell;positive regulation of leukocyte adhesion to arterial endothelial cell;positive regulation of protein localization to cell surface;positive regulation of ceramide biosynthetic process;positive regulation of blood microparticle formation;positive regulation of chemokine (C-X-C motif) ligand 2 production;regulation of endothelial cell apoptotic process;positive regulation of interleukin-6 secretion;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- Cellular component
- phagocytic cup;extracellular region;extracellular space;plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell surface;membrane raft;recycling endosome
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;protease binding;cytokine activity;tumor necrosis factor receptor binding;protein binding;identical protein binding;transcription regulatory region DNA binding