TNFRSF11B

TNF receptor superfamily member 11b, the group of Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 8:118923556-118951885

Previous symbols: [ "OPG" ]

Links

ENSG00000164761 ∙ NCBI:4982 ∙ OMIM:602643 ∙ HGNC:11909 ∙ Uniprot:O00300 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• juvenile Paget disease (Strong), mode of inheritance: AR
• juvenile Paget disease (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Paget disease of bone 5, juvenile	AR	Endocrine; Musculoskeletal	Individuals may present with manifestations including osteopenia, fractures, and progressive skeletal deformity, and medical treatment (eg, with disodium etidronate, bisphosphonates, osteoprotegerin) has been reported as beneficial	Dental; Endocrine; Musculoskeletal	13368018; 14123485; 5675396; 1593590; 8053403; 8770706; 12189164; 12124406; 14672344; 16135836; 17352649 ; 25108083

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNFRSF11B gene.

• not provided (107 variants)
• Hyperphosphatasemia with bone disease (51 variants)
• Inborn genetic diseases (15 variants)
• not specified (6 variants)
• Connective tissue disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNFRSF11B 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			2	19	6	27
missense		1	68		3	72
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	2	4	7
non coding			14	7	6	27
Total	2	1	84	26	15

Highest pathogenic variant AF is 0.00000658

Variants in TNFRSF11B

This is a list of pathogenic ClinVar variants found in the TNFRSF11B region.

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

Position	Type	Phenotype	Significance	ClinVar
8-118923575-C-T		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 13, 2018)
8-118923692-A-G		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 13, 2018)
8-118923765-C-T		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 12, 2018)
8-118923791-A-T		Hyperphosphatasemia with bone disease	Benign (Jan 12, 2018)
8-118923829-A-G		Hyperphosphatasemia with bone disease	Likely benign (Jan 13, 2018)
8-118923869-T-C		Hyperphosphatasemia with bone disease	Uncertain significance (Apr 27, 2017)
8-118923887-A-G		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 13, 2018)
8-118923911-A-T		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 13, 2018)
8-118923962-T-C		Hyperphosphatasemia with bone disease	Uncertain significance (Mar 23, 2018)
8-118924007-C-T		Hyperphosphatasemia with bone disease	Benign (Jan 12, 2018)
8-118924025-A-T		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 13, 2018)
8-118924161-G-A		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 13, 2018)
8-118924167-G-C		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 12, 2018)
8-118924208-G-C		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 13, 2018)
8-118924307-G-A		Hyperphosphatasemia with bone disease	Uncertain significance (Jan 13, 2018)
8-118924375-T-A			Pathogenic (Aug 23, 2023)
8-118924388-T-G			Uncertain significance (May 16, 2022)
8-118924407-G-A			Likely benign (Sep 03, 2023)
8-118924407-G-C			Uncertain significance (Dec 27, 2022)
8-118924414-A-G			Uncertain significance (Jul 07, 2022)
8-118924430-A-G		Hyperphosphatasemia with bone disease	Benign (Jan 29, 2024)
8-118924438-T-C			Uncertain significance (Aug 31, 2023)
8-118924440-C-G			Uncertain significance (Aug 22, 2022)
8-118924469-A-C			Uncertain significance (Aug 05, 2022)
8-118924471-C-T			Uncertain significance (Oct 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNFRSF11B	protein_coding	protein_coding	ENST00000297350	5	28644

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.162	0.838	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.841	184	219	0.840	0.0000123	2667
Missense in Polyphen		34	66.13	0.51414		863
Synonymous	0.570	80	86.8	0.922	0.00000562	711
Loss of Function	3.00	5	19.2	0.260	9.94e-7	229

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000174	0.000174
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000727	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis. {ECO:0000269|PubMed:22664871, ECO:0000269|PubMed:9168977}.
• Disease: DISEASE: Paget disease of bone 5, juvenile-onset (PDB5) [MIM:239000]: An autosomal recessive, juvenile-onset form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. PDB5 clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness. {ECO:0000269|PubMed:12189164}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Osteoclast differentiation - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Osteoclast Signaling;Apoptosis Modulation and Signaling;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Ectoderm Differentiation;Vitamin D Receptor Pathway;Osteoblast Signaling;Monoamine Transport;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;Immune System;TNFs bind their physiological receptors (Consensus)

Recessive Scores

• pRec: 0.603

Intolerance Scores

• loftool: 0.211
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• pHI: 0.283
• hipred: Y
• hipred_score: 0.776
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.706

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnfrsf11b
• Phenotype: cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear 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); 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); hematopoietic system phenotype

Gene ontology

• Biological process: skeletal system development;apoptotic process;signal transduction;response to nutrient;regulation of signaling receptor activity;extracellular matrix organization;response to magnesium ion;tumor necrosis factor-mediated signaling pathway;negative regulation of odontogenesis of dentin-containing tooth;response to drug;response to estrogen;negative regulation of bone resorption;response to arsenic-containing substance
• Cellular component: extracellular region;extracellular space;plasma membrane;extracellular matrix
• Molecular function: cytokine activity;protein binding;signaling receptor activity