TNFRSF21

TNF receptor superfamily member 21, the group of CD molecules|Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 6:47231532-47309905

Links

ENSG00000146072 ∙ NCBI:27242 ∙ OMIM:605732 ∙ HGNC:13469 ∙ Uniprot:O75509 ∙ 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 TNFRSF21 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNFRSF21 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	2
missense			49	1	1	51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	49	1	3

Variants in TNFRSF21

This is a list of pathogenic ClinVar variants found in the TNFRSF21 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-47232878-G-A		not specified	Uncertain significance (Dec 12, 2023)
6-47234685-A-C		not specified	Uncertain significance (Oct 29, 2024)
6-47234773-C-G		not specified	Uncertain significance (Jan 16, 2024)
6-47234782-T-C			Benign (Mar 29, 2018)
6-47234786-G-A		not specified	Uncertain significance (Jan 23, 2024)
6-47234815-C-A		not specified	Uncertain significance (Jul 13, 2022)
6-47234826-C-A		not specified	Uncertain significance (Oct 01, 2024)
6-47234828-T-C		TNFRSF21-related condition	Likely benign (Jun 28, 2024)
6-47234839-G-C		not specified	Uncertain significance (Jun 10, 2022)
6-47234841-T-C		not specified	Uncertain significance (Apr 04, 2023)
6-47234849-G-A		not specified	Uncertain significance (Dec 03, 2024)
6-47253270-C-G		not specified	Uncertain significance (Dec 27, 2023)
6-47253286-C-G		not specified	Uncertain significance (Jan 30, 2024)
6-47253351-C-T		not specified	Uncertain significance (May 31, 2023)
6-47253359-C-T		not specified	Uncertain significance (Jun 21, 2023)
6-47253360-G-A		not specified	Uncertain significance (Jan 19, 2025)
6-47253392-C-T		not specified	Uncertain significance (Feb 06, 2024)
6-47253410-T-C		not specified	Uncertain significance (Feb 03, 2022)
6-47253491-T-C		not specified	Uncertain significance (Oct 09, 2024)
6-47253495-C-A		not specified	Uncertain significance (Nov 01, 2022)
6-47283950-A-T		not specified	Uncertain significance (Apr 25, 2023)
6-47283971-G-A		not specified	Uncertain significance (Sep 29, 2023)
6-47284022-C-T			Benign (Mar 29, 2018)
6-47284069-C-T		not specified	Uncertain significance (Dec 22, 2023)
6-47284070-G-A		not specified	Uncertain significance (Apr 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNFRSF21	protein_coding	protein_coding	ENST00000296861	6	78374

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0406	0.958	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	304	370	0.822	0.0000218	4260
Missense in Polyphen		85	141.55	0.6005		1623
Synonymous	-0.288	158	153	1.03	0.00000941	1348
Loss of Function	2.84	6	19.6	0.307	9.27e-7	247

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000356	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.000136	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm. Plays a role in neuronal apoptosis, including apoptosis in response to amyloid peptides derived from APP, and is required for both normal cell body death and axonal pruning. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP). N-APP binds TNFRSF21; this triggers caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase- 6). Negatively regulates oligodendrocyte survival, maturation and myelination. Plays a role in signaling cascades triggered by stimulation of T-cell receptors, in the adaptive immune response and in the regulation of T-cell differentiation and proliferation. Negatively regulates T-cell responses and the release of cytokines such as IL4, IL5, IL10, IL13 and IFNG by Th2 cells. Negatively regulates the production of IgG, IgM and IgM in response to antigens. May inhibit the activation of JNK in response to T-cell stimulation. {ECO:0000269|PubMed:21725297, ECO:0000269|PubMed:22761420, ECO:0000269|PubMed:9714541}.
• Pathway: Cytokine-cytokine receptor interaction - Homo sapiens (human);Apoptosis;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Apoptosis-related network due to altered Notch3 in ovarian cancer;Cellular response to heat stress;Apoptotic Signaling Pathway;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Cellular responses to external stimuli;Cellular response to heat stress (Consensus)

Recessive Scores

• pRec: 0.228

Intolerance Scores

• loftool: 0.0511
• rvis_EVS: -1
• rvis_percentile_EVS: 8.47

Haploinsufficiency Scores

• pHI: 0.291
• hipred: Y
• hipred_score: 0.853
• ghis: 0.422

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.824

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnfrsf21
• Phenotype: cellular phenotype; homeostasis/metabolism 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); immune 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); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: tnfrsf21
• Affected structure: central artery
• Phenotype tag: abnormal
• Phenotype quality: decreased branchiness

Gene ontology

• Biological process: B cell apoptotic process;adaptive immune response;apoptotic process;humoral immune response;axonal fasciculation;regulation of lipid metabolic process;negative regulation of B cell proliferation;negative regulation of myelination;negative regulation of T cell proliferation;myelination;regulation of oligodendrocyte differentiation;T cell receptor signaling pathway;neuron apoptotic process;cellular response to tumor necrosis factor;oligodendrocyte apoptotic process;negative regulation of interleukin-5 secretion;negative regulation of interleukin-13 secretion;negative regulation of interleukin-10 secretion
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;axon;intrinsic component of plasma membrane