TNFRSF14

Chr 1

TNF receptor superfamily member 14

Also known as: ATAR, CD270, HVEA, HVEM, LIGHTR, TR2

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]

0
Active trials
43
Pubs (1 yr)
62
P/LP submissions
P/LP missense
0.44
LOEUF
GOF
Mechanism· predicted
Clinical SummaryTNFRSF14
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 6 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.808
Z-score 3.00
OE 0.14 (0.060.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.61Z-score
OE missense 0.87 (0.760.99)
151 obs / 173.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.060.44)
00.351.4
Missense OE0.87 (0.760.99)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 2 / 14.2Missense obs/exp: 151 / 173.7Syn Z: -1.23
DN
0.6066th %ile
GOF
0.7127th %ile
LOF
0.4037th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic1
VUS6
Benign1
60
Pathogenic
1
Likely Pathogenic
6
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
60
Likely Pathogenic
1
VUS
6
Likely Benign
0
Benign
1
Total68

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TNFRSF14 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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