BTN3A2

Chr 6

butyrophilin subfamily 3 member A2

Also known as: BT3.2, BTF4, BTN3.2, CD277

NCBI Gene: 11118ENSG00000186470UniProt: P78410

This gene encodes a member of the immunoglobulin superfamily, which resides in the juxta-telomeric region of the major histocompatability class 1 locus and is clustered with the other family members on chromosome 6. The encoded protein may be involved in the adaptive immune response. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

66
ClinVar variants
4
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BTN3A2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 57 VUS of 66 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.
1.42LOEUF
pLI 0.000
Z-score 0.26
OE 0.93 (0.63–1.42)
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.
0.57Z-score
OE missense 0.88 (0.77–1.00)
158 obs / 179.7 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.0.93 (0.63–1.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.77–1.00)
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.0.90
0≤1.21.6
LoF obs/exp: 16 / 17.2Missense obs/exp: 158 / 179.7Syn Z: 0.64

ClinVar Variant Classifications

66 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS57
Likely Benign2
Benign3
4
Pathogenic
57
VUS
2
Likely Benign
3
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
48
9
0
57
Likely Benign
0
2
0
0
2
Benign
1
0
0
2
3
Total15013266

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

View in ClinVar →

Protein Context — Lollipop Plot

BTN3A2 · 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
Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.
Si S et al.·Genome Med
2024
A genetic study to identify pathogenic mechanisms and drug targets for benign prostatic hyperplasia: a multi-omics Mendelian randomization study.
Liu B et al.·Sci Rep
2024Functional
Genome-wide Mendelian randomization mapping the influence of plasma proteome on major depressive disorder.
Li C et al.·J Affect Disord
2025
Exome Array Analysis Identifies Variants in SPOCD1 and BTN3A2 That Affect Risk for Gastric Cancer.
Zhu M et al.·Gastroenterology
2017
Identifying Immune Response Protein Biomarkers in Parkinson's-Related Cognitive Impairment and Depression.
Su Q et al.·Mol Neurobiol
2025
Metabolites downstream of predicted loss-of-function variants inform relationship to disease.
Li M et al.·Mol Genet Metab
2019
Pan-cancer transcriptomic analysis identified six classes of immunosenescence genes revealed molecular links between aging, immune system and cancer.
Wang X et al.·Genes Immun
2023
BTN2A1 and BTN3A1 as Novel Coeliac Disease Risk Loci: An In Silico Analysis.
Luu Hoang KN et al.·Int J Mol Sci
2025
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
Anazi S et al.·Mol Psychiatry
2017
Leveraging lung tissue transcriptome to uncover candidate causal genes in COPD genetic associations.
Lamontagne M et al.·Hum Mol Genet
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
DNA Methylation-mediated BTN3A2 Regulation via CD14+CD16+ Monocytes Protects Against Primary Sclerosing Cholangitis.
Zhou J et al.·Curr Top Med Chem
2026
Multiomics Mendelian randomization integrating pQTL, eQTL and mQTL data revealed BTN3A2 as a potential drug target for nephrolithiasis.
Sun S et al.·Sci Rep
2025🔓 Open Access
Decoding the epigenetic-immune nexus in hepatocellular carcinoma: a Mendelian randomization study reveals BTN3A2, S100A12 and TRIM27 as white blood cell regulators.
Qiu Y et al.·BMC Cancer
2025🔓 Open Access
BTN3A2 interacted with MFGE8 to alleviate preeclampsia by promoting ferroptosis and inhibiting angiogenesis.
Yuan X et al.·Life Sci
2025
Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2.
Xu L et al.·EBioMedicine
2024🔓 Open Access
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