TNFSF18

protein-coding

TNF superfamily member 18, the group of Tumor necrosis factor superfamily

Gene summary

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptor TNFRSF18/AITR/GITR. It has been shown to modulate T lymphocyte survival in peripheral tissues. This cytokine is also found to be expressed in endothelial cells, and is thought to be important for interaction between T lymphocytes and endothelial cells. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005092.4

Inheritance

—

ClinVar variants

U:12B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr1:173,039,202-173,050,941

External References & Databases

Ensembl (ENSG00000120337)

Transcript & Mutation Effects

hg38 • Region Span ~11.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TNFSF18 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005092.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			12 clinvar	1 clinvar		13
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	12	1	0	13

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005092.4	RefSeq	NP_005083.3	3	MANE Select
ENST00000404377.5	Ensembl	ENSP00000385470.4	3	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tnfsf18	Danio rerio	Structure: somite border Quality: irregular spatial pattern abnormal

Gene / Model

Organism

Observed Phenotype

tnfsf18

Danio rerio

Structure: somite border

Quality: irregular spatial pattern

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

adaptive immune response
T cell proliferation involved in immune response
positive regulation of leukocyte migration
signal transduction
cell-cell signaling

Molecular Function

signaling receptor binding
cytokine activity
protein binding
tumor necrosis factor receptor superfamily binding
identical protein binding

Cellular Component

extracellular space
plasma membrane
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000404377
Coding exons: 3
Length: 11004
Individuals with no LoFs: 125421
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125442
p: 0.0000837

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.555	115	99.4	1.16	0.00000447	1302
Missense (PolyPhen)		30	24.495	1.2247		348
Synonymous	0.302	34	36.3	0.936	0.00000165	370
Loss of Function	0.354	6	7.01	0.856	2.95e-7	91

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00065	0.00065	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000096	0.0000088	rare
South Asian	0.00022	0.00020	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cytokine that binds to TNFRSF18/AITR/GITR. Regulates T- cell responses. Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation. Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B. Triggers increased phosphorylation of STAT1 and up-regulates expression of VCAM1 and ICAM1 (PubMed:23892569). Promotes leukocyte adhesion to endothelial cells (PubMed:23892569). Regulates migration of monocytes from the splenic reservoir to sites of inflammation (By similarity). {ECO:0000250|UniProtKB:Q7TS55, ECO:0000269|PubMed:17449724, ECO:0000269|PubMed:18040044, ECO:0000269|PubMed:23892569}.;

Recessive Scores

pRec: 0.174

Intolerance Scores

LoFtool: 0.533
RVIS EVS: -0.05
RVIS percentile EVS: 49.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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