TNFRSF14

protein-coding

TNF receptor superfamily member 14, the group of CD molecules|Tumor necrosis factor receptor superfamily

Gene summary

This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MANE transcript

NM_003820.4

Inheritance

—

ClinVar variants

U:56B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr1:2,555,639-2,565,382

External References & Databases

Ensembl (ENSG00000157873)

Transcript & Mutation Effects

hg38 • Region Span ~9.7 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 TNFRSF14 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003820.4. 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			4 clinvar		1 clinvar	5
missense			40 clinvar	1 clinvar		41
nonsense			2 clinvar			2
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	56	1	1	58

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003820.4	RefSeq	NP_003811.2	8	MANE Select
ENST00000355716.5	Ensembl	ENSP00000347948.4	8	MANE Select
NM_001297605.2	RefSeq	NP_001284534.1	6	Standard
ENST00000409119.5	Ensembl	ENSP00000386859.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cytokine-cytokine receptor interaction - Homo sapiens (human)
Herpes simplex infection - Homo sapiens (human)
TNFR2 non-canonical NF-kB pathway
Cytokine Signaling in Immune system
Costimulation by the CD28 family

Biological Process

positive regulation of cytokine secretion involved in immune response
immune response
cell surface receptor signaling pathway
T cell costimulation
tumor necrosis factor-mediated signaling pathway

Molecular Function

virus receptor activity
tumor necrosis factor-activated receptor activity
protein binding
ubiquitin protein ligase binding

Cellular Component

plasma membrane
external side of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355716
Coding exons: 8
Length: 9744
Individuals with no LoFs: 125098
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125101
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.613	151	174	0.869	0.0000106	1800
Missense (PolyPhen)		22	40.59	0.54201		459
Synonymous	-1.23	90	76.3	1.18	0.00000576	546
Loss of Function	3.00	2	14.2	0.141	6.05e-7	164

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000019	0.000018	rare
South Asian	0	0.0	absent
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for BTLA. Receptor for TNFSF14/LIGHT and homotrimeric TNFSF1/lymphotoxin-alpha. Involved in lymphocyte activation. Plays an important role in HSV pathogenesis because it enhanced the entry of several wild-type HSV strains of both serotypes into CHO cells, and mediated HSV entry into activated human T-cells. {ECO:0000269|PubMed:8898196}.; FUNCTION: (Microbial infection) Acts as a receptor for Herpes simplex virus 2/HHV-2. {ECO:0000269|PubMed:11511370, ECO:0000269|PubMed:9696799}.;

Recessive Scores

pRec: 0.215

Intolerance Scores

LoFtool: 0.186
RVIS EVS: 0.13
RVIS percentile EVS: 63.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.860

Gene Damage Prediction

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