TNFRSF9

TNF receptor superfamily member 9, the group of CD molecules|Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 1:7915871-7943165

Previous symbols: [ "ILA" ]

Links

ENSG00000049249 ∙ NCBI:3604 ∙ OMIM:602250 ∙ HGNC:11924 ∙ Uniprot:Q07011 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 109 with lymphoproliferation (Moderate), mode of inheritance: AR
• immunodeficiency 109 with lymphoproliferation (Definitive), mode of inheritance: AR
• immunodeficiency 109 with lymphoproliferation (Strong), mode of inheritance: AR
• immunodeficiency 109 with lymphoproliferation (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 109 with lymphoproliferation	AR	Allergy/Immunology/Infectious; Oncologic	Individuals have been described as having a primary immunodeficiency, with susceptibility to sinopulmonary and other infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals have been described as developing lymphoma and HLH, and awareness may allow early recognition and management; HSCT has been described	Allergy/Immunology/Infectious; Oncologic	30872117

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNFRSF9 gene.

• not_provided (173 variants)
• Inborn_genetic_diseases (31 variants)
• TNFRSF9-related_disorder (6 variants)
• not_specified (5 variants)
• Immunodeficiency_109_with_lymphoproliferation (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNFRSF9 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001561.6. 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			3	42	3	48
missense	1		70	5	1	77
nonsense	2	1	1			4
start loss						0
frameshift	6	1				7
splice donor/acceptor (+/-2bp)	1	2	1			4
Total	10	4	75	47	4

Highest pathogenic variant AF is 0.000044575256

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNFRSF9	protein_coding	protein_coding	ENST00000377507	7	21020

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125730	0	17	125747	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.364	134	146	0.915	0.00000810	1666
Missense in Polyphen		25	33.399	0.74853		420
Synonymous	-0.00761	56	55.9	1.00	0.00000346	476
Loss of Function	2.54	3	12.8	0.234	6.98e-7	149

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for TNFSF9/4-1BBL. Possibly active during T cell activation.
• Pathway: Cytokine-cytokine receptor interaction - Homo sapiens (human);T-Cell antigen Receptor (TCR) Signaling Pathway;the 41bb-dependent immune response;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)

Recessive Scores

• pRec: 0.281

Intolerance Scores

• loftool: 0.334
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.13

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.545

Gene Damage Prediction

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

Gene ontology

• Biological process: apoptotic process;negative regulation of cell population proliferation;tumor necrosis factor-mediated signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;external side of plasma membrane
• Molecular function: signaling receptor activity