BTN1A1

Chr 6

butyrophilin subfamily 1 member A1

Also known as: BT, BTN, BTN1

NCBI Gene: 696ENSG00000124557UniProt: Q13410

Butyrophilin is the major protein associated with fat droplets in the milk. It is a member of the immunoglobulin superfamily. It may have a cell surface receptor function. The human butyrophilin gene is localized in the major histocompatibility complex (MHC) class I region of 6p and may have arisen relatively recently in evolution by the shuffling of exons between 2 ancestral gene families [provided by RefSeq, Jul 2008]

82
ClinVar variants
4
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BTN1A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 72 VUS of 82 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.
1.08LOEUF
pLI 0.000
Z-score 1.26
OE 0.70 (0.47–1.08)
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.
1.32Z-score
OE missense 0.78 (0.70–0.87)
229 obs / 292.6 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.0.70 (0.47–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.70–0.87)
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.0.80
0≤1.21.6
LoF obs/exp: 15 / 21.3Missense obs/exp: 229 / 292.6Syn Z: 1.67

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS72
Likely Benign3
Benign3
4
Pathogenic
72
VUS
3
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
66
6
0
72
Likely Benign
0
3
0
0
3
Benign
0
2
0
1
3
Total07110182

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

View in ClinVar →

Protein Context — Lollipop Plot

BTN1A1 · 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
Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes.
Li Q et al.·Comput Biol Med
2023Functional
Multi-omic biomarkers associated with multiple sclerosis: from Mendelian randomization to drug prediction.
Yang W et al.·Sci Rep
2025
Novel drug resistance mechanisms and drug targets in BRAF-mutated peritoneal metastasis from colorectal cancer.
Lund-Andersen C et al.·J Transl Med
2024Functional
Neonatal enteroids absorb extracellular vesicles from human milk-fed infant digestive fluid.
Yung C et al.·J Extracell Vesicles
2024
Exploring new drug treatment targets for immune related bone diseases using a multi omics joint analysis strategy.
Yang W et al.·Sci Rep
2025
TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh.
Zhao L et al.·Nat Commun
2020
Plasma proteins and different onset subtype of COPD: Proteome-wide Mendelian randomization study and co-localization analyses.
Chu X et al.·Medicine (Baltimore)
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
BTN1A1 is a novel immune checkpoint mutually exclusive to PD-L1.
Kim YS et al.·J Immunother Cancer
2024🔓 Open Access
[Effects of auricular thumbtack needle on lactation function and TDP-43/Btn1A1/XDH pathway in primiparous women with cesarean section].
Lin QP et al.·Zhongguo Zhen Jiu
2023
Occludin is a target of Src kinase and promotes lipid secretion by binding to BTN1a1 and XOR.
Lu Y et al.·PLoS Biol
2022🔓 Open Access
The butyrophilin 1a1 knockout mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation.
Jeong J et al.·FASEB Bioadv
2021🔓 Open AccessFunctional
Knockout of butyrophilin subfamily 1 member A1 (BTN1A1) alters lipid droplet formation and phospholipid composition in bovine mammary epithelial cells.
Han L et al.·J Anim Sci Biotechnol
2020🔓 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