BTN3A1

Chr 6

butyrophilin subfamily 3 member A1

Also known as: BT3.1, BTF5, BTN3.1, CD277

NCBI Gene: 11119ENSG00000026950UniProt: O00481

The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A1) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]).[supplied by OMIM, Nov 2010]

77
ClinVar variants
4
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BTN3A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 65 VUS of 77 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.19LOEUF
pLI 0.000
Z-score 0.92
OE 0.78 (0.52–1.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.18Z-score
OE missense 0.97 (0.87–1.07)
261 obs / 269.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.78 (0.52–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.87–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.72
0≤1.21.6
LoF obs/exp: 15 / 19.4Missense obs/exp: 261 / 269.5Syn Z: 2.28

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS65
Likely Benign7
Benign1
4
Pathogenic
65
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
0
0
0
VUS
0
57
8
0
65
Likely Benign
0
6
1
0
7
Benign
0
0
0
1
1
Total06313177

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BTN3A1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
BTN3A1 expressed in cervical cancer cells promotes Vγ9Vδ2 T cells exhaustion through upregulating transcription factors NR4A2/3 downstream of TCR signaling.
Liu J et al.·Cell Commun Signal
2024
Genetic insights into therapeutic targets for aortic aneurysms: A Mendelian randomization study.
Chen Y et al.·EBioMedicine
2022
Comprehensive analysis of BTN3A1 in cancers: mining of omics data and validation in patient samples and cellular models.
Liang F et al.·FEBS Open Bio
2021Functional
High expression of BTN3A1 is associated with clinical and immunological characteristics and predicts a poor prognosis in advanced human gliomas.
Kone AS et al.·Front Immunol
2024
BTN3A1 promotes tumor progression and radiation resistance in esophageal squamous cell carcinoma by regulating ULK1-mediated autophagy.
Yang W et al.·Cell Death Dis
2022
Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis.
Mayer LS et al.·Sci Immunol
2026
A regulatory variant rs9379874 in T1D risk region 6p22.2 affects BTN3A1 expression regulating T cell function.
Jiang L et al.·Acta Diabetol
2025
SIRPA, BTN3A1, and TDO2 in osteosarcoma: a prognostic triad with therapeutic implications from integrated genomic and pharmacogenomic data.
Zhang HJ et al.·J Orthop Surg Res
2025
Construction and validation of an oxidative-stress-related risk model for predicting the prognosis of osteosarcoma.
Wang H et al.·Aging (Albany NY)
2023Functional
The making of multivalent gamma delta TCR anti-CD3 bispecific T cell engagers.
van Diest E et al.·Front Immunol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools