TNFRSF4

TNF receptor superfamily member 4, the group of CD molecules|Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 1:1211326-1214153

Previous symbols: [ "TXGP1L" ]

Links

ENSG00000186827 ∙ NCBI:7293 ∙ OMIM:600315 ∙ HGNC:11918 ∙ Uniprot:P43489 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined immunodeficiency due to OX40 deficiency (Limited), mode of inheritance: AR
• combined immunodeficiency due to OX40 deficiency (Limited), mode of inheritance: AR
• combined immunodeficiency due to OX40 deficiency (Limited), mode of inheritance: Unknown
• combined immunodeficiency due to OX40 deficiency (Supportive), mode of inheritance: AR
• combined immunodeficiency due to OX40 deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 16	AR	Allergy/Immunology/Infectious	Individuals may be susceptible to severe infections, as well as related oncologic sequelae (eg, Kaposi sarcoma), and early and aggressive treatment of infections and related sequelae may be beneficial	Allergy/Immunology/Infectious	20156905; 23897980

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNFRSF4 gene.

• Combined_immunodeficiency_due_to_OX40_deficiency (335 variants)
• not_specified (54 variants)
• not_provided (19 variants)
• TNFRSF4-related_disorder (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNFRSF4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003327.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	80	5	89
missense			147	10	1	158
nonsense			1			1
start loss			1			1
frameshift			10			10
splice donor/acceptor (+/-2bp)			6			6
Total	0	0	169	90	6

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNFRSF4	protein_coding	protein_coding	ENST00000379236	7	2813

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124534	0	19	124553	0.0000763

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.623	142	164	0.863	0.0000110	1712
Missense in Polyphen		26	38.092	0.68256		467
Synonymous	0.163	73	74.8	0.976	0.00000549	583
Loss of Function	0.860	7	9.92	0.705	4.22e-7	130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000157	0.000154
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000999	0.0000929
European (Non-Finnish)	0.000129	0.000125
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule implicated in long-term T-cell immunity. {ECO:0000269|PubMed:7704935}.
• Disease: DISEASE: Immunodeficiency 16 (IMD16) [MIM:615593]: An autosomal recessive primary immunodeficiency associated with classic Kaposi sarcoma of childhood and poor T-cell recall immune responses due to complete functional OX40 deficiency. {ECO:0000269|PubMed:23897980}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cytokine-cytokine receptor interaction - Homo sapiens (human);TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;Immune System;TNFs bind their physiological receptors;Downstream signaling in naïve CD8+ T cells (Consensus)

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.604

Gene Damage Prediction

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

Gene ontology

• Biological process: inflammatory response;immune response;cellular defense response;positive regulation of B cell proliferation;tumor necrosis factor-mediated signaling pathway;T cell proliferation;negative regulation of DNA-binding transcription factor activity;regulation of protein kinase activity;negative regulation of transcription, DNA-templated;viral entry into host cell;negative regulation of cytokine secretion;positive regulation of immunoglobulin secretion;negative regulation of activation-induced cell death of T cells;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell surface
• Molecular function: virus receptor activity;tumor necrosis factor-activated receptor activity;protein binding