TNFRSF10B

TNF receptor superfamily member 10b, the group of CD molecules|Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 8:23020133-23069031

Links

ENSG00000120889 ∙ NCBI:8795 ∙ OMIM:603612 ∙ HGNC:11905 ∙ Uniprot:O14763 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• head and neck squamous cell carcinoma (Limited), mode of inheritance: AD
• head and neck squamous cell carcinoma (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Squamous cell carcinoma, head and neck	AD	Oncologic	Surveillance and early diagnosis could potentially be beneficial to allow prompt management of detected neoplasms	Oncologic	9721851

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNFRSF10B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNFRSF10B 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				8		8
missense			23	5	3	31
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				2		2
Total	0	1	23	15	3

Variants in TNFRSF10B

This is a list of pathogenic ClinVar variants found in the TNFRSF10B region.

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

Position	Type	Phenotype	Significance	ClinVar
8-23022666-C-A		TNFRSF10B-related disorder	Likely benign (Jun 25, 2019)
8-23022706-A-G		not specified	Uncertain significance (Apr 17, 2024)
8-23022808-C-T		not specified	Uncertain significance (Dec 20, 2023)
8-23022843-G-A		not specified	Uncertain significance (Dec 13, 2022)
8-23022842-C-CGT		Squamous cell carcinoma of the head and neck	Pathogenic (Aug 15, 1998)
8-23022867-G-A		not specified	Uncertain significance (Sep 01, 2021)
8-23022920-C-T		not specified	Uncertain significance (Nov 21, 2022)
8-23022946-G-A		not specified	Uncertain significance (Oct 29, 2021)
8-23022949-C-A		not specified	Uncertain significance (May 16, 2022)
8-23022960-A-C		not specified	Uncertain significance (Jun 05, 2023)
8-23024256-G-A		not specified	Uncertain significance (Jul 13, 2021)
8-23027150-C-T		not specified	Uncertain significance (Apr 19, 2023)
8-23027164-A-G		not specified	Likely benign (Apr 04, 2023)
8-23027224-G-T		not specified	Uncertain significance (Oct 12, 2021)
8-23027270-C-G		not specified	Uncertain significance (Nov 07, 2022)
8-23027733-G-A		TNFRSF10B-related disorder	Likely benign (Jul 25, 2022)
8-23028334-A-T		not specified	Uncertain significance (Jun 29, 2023)
8-23028342-C-A		not specified	Uncertain significance (Apr 08, 2022)
8-23028346-T-G		not specified	Uncertain significance (Mar 15, 2024)
8-23028394-C-A		not specified	Uncertain significance (Jan 04, 2022)
8-23028402-A-G		not specified	Uncertain significance (May 23, 2023)
8-23028422-T-C		TNFRSF10B-related disorder	Likely benign (Mar 17, 2020)
8-23028446-G-A			Likely benign (Nov 09, 2018)
8-23028480-GA-G		Squamous cell carcinoma of the head and neck	Likely pathogenic (Apr 04, 2024)
8-23028507-A-G		TNFRSF10B-related disorder	Benign (Sep 24, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNFRSF10B	protein_coding	protein_coding	ENST00000276431	9	49047

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000199	0.979	125648	0	100	125748	0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.670	270	241	1.12	0.0000128	2826
Missense in Polyphen		48	53.824	0.89179		721
Synonymous	-0.224	102	99.2	1.03	0.00000584	892
Loss of Function	2.05	9	18.5	0.486	8.95e-7	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000796	0.000796
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000571	0.000571
Middle Eastern	0.00	0.00
South Asian	0.000232	0.000229
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:10549288). 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. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis. {ECO:0000269|PubMed:10542098, ECO:0000269|PubMed:10549288, ECO:0000269|PubMed:15322075}.
• Disease: DISEASE: Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: p53 signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Necroptosis - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Measles - Homo sapiens (human);Apoptosis - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);miRNA Regulation of DNA Damage Response;Apoptosis Modulation and Signaling;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Apoptosis;Apoptosis-related network due to altered Notch3 in ovarian cancer;Apoptotic Signaling Pathway;TP53 Regulates Transcription of Cell Death Genes;miRNA regulation of p53 pathway in prostate cancer;DNA Damage Response;Signal Transduction;Gene expression (Transcription);induction of apoptosis through dr3 and dr4/5 death receptors;Generic Transcription Pathway;TP53 Regulates Transcription of Cell Death Genes;Regulation of necroptotic cell death;Dimerization of procaspase-8;Regulation by c-FLIP;Ligand-dependent caspase activation;RNA Polymerase II Transcription;Caspase activation via extrinsic apoptotic signalling pathway;Apoptosis;CASP8 activity is inhibited;Regulated Necrosis;Programmed Cell Death;RIPK1-mediated regulated necrosis;TRAIL signaling;Cell surface interactions at the vascular wall;Hemostasis;Death Receptor Signalling;Transcriptional Regulation by TP53;Direct p53 effectors;Caspase Cascade in Apoptosis;TRAIL signaling pathway;TP53 Regulates Transcription of Death Receptors and Ligands (Consensus)

Intolerance Scores

• loftool: 0.196
• rvis_EVS: 0.64
• rvis_percentile_EVS: 84.05

Haploinsufficiency Scores

• pHI: 0.172
• hipred: N
• hipred_score: 0.327
• ghis: 0.452

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.479

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnfrsf10b
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; immune 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; neoplasm

Gene ontology

• Biological process: apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;cell surface receptor signaling pathway;activation of NF-kappaB-inducing kinase activity;extrinsic apoptotic signaling pathway via death domain receptors;response to endoplasmic reticulum stress;TRAIL-activated apoptotic signaling pathway;regulation of apoptotic process;positive regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;leukocyte migration;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;cellular response to mechanical stimulus;regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• Cellular component: plasma membrane;cell surface;integral component of membrane
• Molecular function: protein binding;signaling receptor activity;TRAIL binding