TRAF2

TNF receptor associated factor 2, the group of TNF receptor associated factors|MicroRNA protein coding host genes|Ring finger proteins|Zinc fingers TRAF-type

Basic information

Region (hg38): 9:136881911-136926607

Links

ENSG00000127191 ∙ NCBI:7186 ∙ OMIM:601895 ∙ HGNC:12032 ∙ Uniprot:Q12933 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAF2 gene.

• Inborn genetic diseases (19 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAF2 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					3	3
missense			18	1		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	1	3

Variants in TRAF2

This is a list of pathogenic ClinVar variants found in the TRAF2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-136898748-C-T		not specified	Uncertain significance (Jan 24, 2024)
9-136898895-G-A		not specified	Uncertain significance (Nov 02, 2023)
9-136898904-C-T		not specified	Uncertain significance (Aug 02, 2021)
9-136898924-C-T		not specified	Uncertain significance (Apr 03, 2023)
9-136899648-C-T			Benign (Jul 17, 2018)
9-136899649-A-C		not specified	Uncertain significance (Aug 15, 2023)
9-136900452-G-T		not specified	Uncertain significance (Aug 30, 2021)
9-136908074-G-T		not specified	Uncertain significance (Dec 01, 2022)
9-136908133-C-T		not specified	Uncertain significance (Aug 29, 2022)
9-136908151-C-T		not specified	Uncertain significance (Oct 20, 2021)
9-136909938-C-T		not specified	Uncertain significance (Feb 28, 2023)
9-136909980-A-T		not specified	Uncertain significance (Jul 06, 2021)
9-136916591-C-G		not specified	Uncertain significance (Feb 21, 2024)
9-136920237-G-A		not specified	Uncertain significance (Sep 27, 2021)
9-136920264-G-C		not specified	Uncertain significance (Dec 20, 2023)
9-136920304-C-T		not specified	Uncertain significance (May 26, 2023)
9-136920346-C-T		not specified	Likely benign (Oct 05, 2021)
9-136920348-G-A		not specified	Uncertain significance (Jan 31, 2024)
9-136920479-G-T			Benign (Aug 16, 2018)
9-136921160-C-T			Benign (Apr 24, 2018)
9-136921183-T-C		not specified	Uncertain significance (Aug 15, 2023)
9-136921192-G-A		not specified	Uncertain significance (May 31, 2022)
9-136923971-G-A		not specified	Uncertain significance (Dec 03, 2021)
9-136925746-G-A		not specified	Uncertain significance (May 01, 2022)
9-136925848-G-A		not specified	Uncertain significance (Jan 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAF2	protein_coding	protein_coding	ENST00000247668	10	44696

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000208	125740	0	5	125745	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	252	332	0.759	0.0000221	3282
Missense in Polyphen		26	80.22	0.32411		819
Synonymous	-2.34	179	143	1.25	0.0000110	975
Loss of Function	4.56	0	24.2	0.00	0.00000118	273

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'- linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin- protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE. {ECO:0000269|PubMed:10346818, ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:11907583, ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:18981220, ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:19506082, ECO:0000269|PubMed:19810754, ECO:0000269|PubMed:19918265, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20047764, ECO:0000269|PubMed:20064526, ECO:0000269|PubMed:20385093, ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:23453969}.
• Pathway: Adipocytokine signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;TNF alpha Signaling Pathway;Integrated Lung Cancer Pathway;Apoptosis;Photodynamic therapy-induced AP-1 survival signaling.;Apoptotic Signaling Pathway;MAPK Signaling Pathway;RIG-I-like Receptor Signaling;Oxidative Damage;p38 MAPK Signaling Pathway;TWEAK;Signal Transduction;tnfr1 signaling pathway;tnfr2 signaling pathway;yaci and bcma stimulation of b cell immune responses;induction of apoptosis through dr3 and dr4/5 death receptors;hiv-1 nef: negative effector of fas and tnf;tnf/stress related signaling;the 41bb-dependent immune response;keratinocyte differentiation;TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;Post-translational protein modification;TRAF6 mediated IRF7 activation;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Metabolism of proteins;Regulation of necroptotic cell death;Dimerization of procaspase-8;Regulation by c-FLIP;Ligand-dependent caspase activation;Caspase activation via extrinsic apoptotic signalling pathway;Innate Immune System;Immune System;Apoptosis;CASP8 activity is inhibited;Regulated Necrosis;Programmed Cell Death;RIPK1-mediated regulated necrosis;ceramide signaling pathway;TNFR1-induced NFkappaB signaling pathway;TNFR1-induced proapoptotic signaling;TNF signaling;sodd/tnfr1 signaling pathway;Ub-specific processing proteases;Deubiquitination;Death Receptor Signalling;Regulation of TNFR1 signaling;TNFalpha;TNF;RANKL;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;CD40/CD40L signaling;TRAIL signaling pathway;TNF receptor signaling pathway ;p38 MAPK signaling pathway;Ceramide signaling pathway (Consensus)

Recessive Scores

• pRec: 0.187

Intolerance Scores

• loftool: 0.165
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.77

Haploinsufficiency Scores

• pHI: 0.393
• hipred: Y
• hipred_score: 0.825
• ghis: 0.611

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Traf2
• Phenotype: 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); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; hematopoietic 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); immune system phenotype

Gene ontology

• Biological process: positive regulation of T cell cytokine production;activation of cysteine-type endopeptidase activity involved in apoptotic process;signal transduction;I-kappaB kinase/NF-kappaB signaling;activation of NF-kappaB-inducing kinase activity;regulation of tumor necrosis factor-mediated signaling pathway;protein deubiquitination;protein catabolic process;positive regulation of interleukin-2 production;tumor necrosis factor-mediated signaling pathway;negative regulation of glial cell apoptotic process;cellular protein-containing complex assembly;response to endoplasmic reticulum stress;regulation of apoptotic process;positive regulation of JUN kinase activity;regulation of immunoglobulin secretion;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;protein heterooligomerization;protein autoubiquitination;protein-containing complex assembly;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;protein homotrimerization;protein K63-linked ubiquitination;death-inducing signaling complex assembly;cellular response to nitric oxide;positive regulation of protein homodimerization activity;programmed necrotic cell death;negative regulation of neuron death;regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;positive regulation of tumor necrosis factor-mediated signaling pathway;positive regulation of I-kappaB phosphorylation;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: ubiquitin ligase complex;nucleoplasm;cytosol;cell cortex;cytoplasmic side of plasma membrane;vesicle membrane;protein-containing complex;CD40 receptor complex;membrane raft;TRAF2-GSTP1 complex;AIP1-IRE1 complex;IRE1-TRAF2-ASK1 complex
• Molecular function: ubiquitin-protein transferase activity;tumor necrosis factor receptor binding;CD40 receptor binding;protein binding;zinc ion binding;enzyme binding;protein kinase binding;protein phosphatase binding;mitogen-activated protein kinase kinase kinase binding;ubiquitin protein ligase binding;thioesterase binding;identical protein binding;protein-containing complex binding;sphingolipid binding