BTN1A1

Summary

BTN1A1 (butyrophilin subfamily 1 member A1, HGNC:1135) is a protein-coding gene on chromosome 6p22.2, encoding Butyrophilin subfamily 1 member A1 (Q13410). May function in the secretion of milk-fat droplets.

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

Source: NCBI Gene 696 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_001732

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1135
Approved symbol	BTN1A1
Name	butyrophilin subfamily 1 member A1
Location	6p22.2
Locus type	gene with protein product
Status	Approved
Aliases	BT, BTN1
Ensembl gene	ENSG00000124557
Ensembl biotype	protein_coding
OMIM	601610
Entrez	696

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000244513, ENST00000684113

RefSeq mRNA: 1 — MANE Select: NM_001732 NM_001732

CCDS: CCDS4614

Canonical transcript exons

ENST00000684113 — 8 exons

Exon	Start	End
ENSE00000703576	26501590	26501937
ENSE00000703580	26506683	26506832
ENSE00000848291	26504925	26505206
ENSE00001038847	26508061	26508087
ENSE00001233265	26507950	26507970
ENSE00003919829	26501230	26501365
ENSE00003920232	26500303	26500358
ENSE00003921633	26508501	26510425

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 92.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0159 / max 7.3217, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66532	0.0159	5

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.22	gold quality
pancreatic ductal cell	CL:0002079	58.28	silver quality
colonic epithelium	UBERON:0000397	54.80	gold quality
bone marrow cell	CL:0002092	54.67	gold quality
lymph node	UBERON:0000029	54.27	gold quality
tibialis anterior	UBERON:0001385	54.03	silver quality
ileal mucosa	UBERON:0000331	51.72	silver quality
deltoid	UBERON:0001476	51.59	gold quality
vermiform appendix	UBERON:0001154	50.96	gold quality
epithelial cell of pancreas	CL:0000083	50.90	gold quality
caecum	UBERON:0001153	49.63	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
quadriceps femoris	UBERON:0001377	49.26	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
oviduct epithelium	UBERON:0004804	48.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
stromal cell of endometrium	CL:0002255	47.88	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	87.73
E-ENAD-17	no	10.12
E-ANND-3	no	3.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SOX9

miRNA regulators (miRDB)

49 targeting BTN1A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-3125	99.14	68.49	2269

Literature-anchored findings (GeneRIF, showing 3)

• PRY/SPRY/B30.2 domain of butyrophilin 1A1 (BTN1A1) binds to xanthine oxidoreductase (PMID:19531472)
• Data illustrated the importance of Akt1 in mammary epithelial cell proliferation, as well as in the regulation of Btn1a1 and subsequent expression of ss-casein. (PMID:21915327)
• BTN1A1 is a novel immune checkpoint mutually exclusive to PD-L1. (PMID:38485289)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Btn1a1	ENSMUSG00000000706
rattus_norvegicus	Btn1a1	ENSRNOG00000017514

Paralogs (15): BTN3A1 (ENSG00000026950), CD276 (ENSG00000103855), BTN3A3 (ENSG00000111801), BTN2A1 (ENSG00000112763), BTNL8 (ENSG00000113303), HHLA2 (ENSG00000114455), BTN2A2 (ENSG00000124508), VTCN1 (ENSG00000134258), ICOSLG (ENSG00000160223), ERMAP (ENSG00000164010), BTNL9 (ENSG00000165810), BTNL3 (ENSG00000168903), BTN3A2 (ENSG00000186470), BTNL2 (ENSG00000204290), MOG (ENSG00000204655)

Protein

Protein identifiers

Butyrophilin subfamily 1 member A1 — Q13410 (reviewed: Q13410)

All UniProt accessions (1): Q13410

UniProt curated annotations — full annotation on UniProt →

Function. May function in the secretion of milk-fat droplets. May act as a specific membrane-associated receptor for the association of cytoplasmic droplets with the apical plasma membrane. Inhibits the proliferation of CD4 and CD8 T-cells activated by anti-CD3 antibodies, T-cell metabolism and IL2 and IFNG secretion.

Subunit / interactions. Seems to associate with xanthine dehydrogenase/oxidase.

Subcellular location. Membrane. Secreted.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the immunoglobulin superfamily. BTN/MOG family.

RefSeq proteins (1): NP_001723* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001870	B30.2/SPRY	Domain
IPR003599	Ig_sub	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037958	SPRY/PRY_BTN1/2	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050504	IgSF_BTN/MOG-like	Family
IPR053896	BTN3A2-like_Ig-C	Domain

Pfam: PF00622, PF07686, PF13765, PF22705

UniProt features (19 total): sequence variant 4, domain 3, compositionally biased region 2, glycosylation site 2, disulfide bond 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13410-F1	84.67	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 50–124, 164–218

Glycosylation sites (2): 55, 215

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8851680	Butyrophilin (BTN) family interactions
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 77 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_CYTOKINE_PRODUCTION, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, MODULE_99, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY, MORF_RAB3A, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, GOMF_SIGNALING_RECEPTOR_BINDING, GOCC_SIDE_OF_MEMBRANE, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP

GO Biological Process (2): regulation of cytokine production (GO:0001817), T cell receptor signaling pathway (GO:0050852)

GO Molecular Function (3): signaling receptor binding (GO:0005102), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
antigen receptor-mediated signaling pathway	1
protein binding	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTN1A1	XDH	P47989	987
BTN1A1	PLIN2	Q99541	972
BTN1A1	MFGE8	Q08431	777
BTN1A1	CSN2	P05814	660
BTN1A1	LTF	P02788	628
BTN1A1	MUC1	P13931	610
BTN1A1	PPL	O60437	563
BTN1A1	CD8A	P01732	563
BTN1A1	MUC15	Q8N387	549
BTN1A1	CSN1S1	P47710	544
BTN1A1	CIDEA	O60543	539
BTN1A1	GOT2	P00505	533
BTN1A1	LALBA	P00709	520
BTN1A1	CD4	P01730	514
BTN1A1	PRY	O14603	476

IntAct

23 interactions, top by confidence:

A	B	Type	Score
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
DCX	ZBTB5	psi-mi:“MI:0914”(association)	0.670
BTN1A1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
BTN1A1	MOSPD2	psi-mi:“MI:0915”(physical association)	0.560
CTLA4	B4GALT5	psi-mi:“MI:0914”(association)	0.530
BTN1A1	PPL	psi-mi:“MI:0915”(physical association)	0.400
BTN1A1	JAML	psi-mi:“MI:0915”(physical association)	0.400
BTN1A1	NEGR1	psi-mi:“MI:0915”(physical association)	0.400
TARM1	BTN1A1	psi-mi:“MI:0915”(physical association)	0.400
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
PLK1	ERCC6L	psi-mi:“MI:0914”(association)	0.350
NME5	INPPL1	psi-mi:“MI:0914”(association)	0.350
TRIM11	LYPLA1	psi-mi:“MI:0914”(association)	0.350
ATG4A	RAB13	psi-mi:“MI:0914”(association)	0.350
ACTBL2	BTN1A1	psi-mi:“MI:0914”(association)	0.350
SSRP1	FABP3	psi-mi:“MI:0914”(association)	0.350
FHIP2A	MED19	psi-mi:“MI:2364”(proximity)	0.270
BTN1A1	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
MOSPD2	BTN1A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): BTN1A1 (Affinity Capture-MS), BTN1A1 (Affinity Capture-MS), BTN1A1 (Affinity Capture-MS), BTN1A1 (Affinity Capture-MS), BTN1A1 (Two-hybrid), MOSPD2 (Two-hybrid), BTN1A1 (Affinity Capture-MS), BTN1A1 (Affinity Capture-MS), BTN1A1 (Affinity Capture-MS), BTN1A1 (Affinity Capture-MS), BTN1A1 (Affinity Capture-MS), BTN1A1 (Protein-RNA), BTN1A1 (Affinity Capture-MS), BTN1A1 (Cross-Linking-MS (XL-MS)), BTN1A1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0E4BZH1, A4QPC6, A5D7V5, A7TZE6, A7TZF0, A7TZF3, A7XUX6, A7XV04, A7XV07, A8K4G0, A8MVZ5, O70355, P08508, P18892, P24071, P31994, P55803, P78410, P79391, Q13410, Q16653, Q29ZQ1, Q3KPI0, Q58DF9, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6Q8B3, Q6UXZ3, Q6XJV4, Q6XJV6, Q7KYR7, Q7TST0, Q7YR73, Q8BTP3, Q8K249, Q8TD46

Diamond homologs: A0A0E4BZH1, A4QPC6, A7TZE6, A7TZF0, A7TZF3, A7TZG1, A7TZG3, A7XUX6, A7XUY5, A7XUZ6, A7XV04, A7XV07, A7XV14, A8MVZ5, O00478, O00481, O70355, P18892, P55803, P78410, Q13410, Q16653, Q29ZQ1, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6MG97, Q6UX41, Q6UXE8, Q6UXG8, Q7KYR7, Q7TST0, Q8BJE2, Q8WVV5, Q96KV6, Q96PL5, Q9BGS7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

77 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

587 predictions. Top by Δscore:

Variant	Effect	Δscore
6:26501933:GGCTG:G	donor_gain	1.0000
6:26501934:GCTGG:G	donor_gain	1.0000
6:26501935:CTGG:C	donor_loss	1.0000
6:26501936:TG:T	donor_gain	1.0000
6:26501937:GG:G	donor_gain	1.0000
6:26501938:G:GG	donor_gain	1.0000
6:26501938:GT:G	donor_loss	1.0000
6:26501939:T:A	donor_loss	1.0000
6:26501940:G:GT	donor_loss	1.0000
6:26508499:A:AG	acceptor_gain	1.0000
6:26508500:G:GA	acceptor_gain	1.0000
6:26501584:C:CA	acceptor_gain	0.9900
6:26501588:A:AG	acceptor_gain	0.9900
6:26501589:G:GG	acceptor_gain	0.9900
6:26501941:A:AC	donor_loss	0.9900
6:26508499:AGTT:A	acceptor_gain	0.9900
6:26508500:GTT:G	acceptor_gain	0.9900
6:26508500:GTTG:G	acceptor_gain	0.9900
6:26501362:TCAGG:T	donor_loss	0.9800
6:26501363:CAGGT:C	donor_loss	0.9800
6:26501364:AGGTA:A	donor_loss	0.9800
6:26501366:G:A	donor_loss	0.9800
6:26501367:T:G	donor_loss	0.9800
6:26501585:G:A	acceptor_gain	0.9800
6:26501933:GGCT:G	donor_gain	0.9800
6:26501934:GCTG:G	donor_gain	0.9800
6:26504923:A:AG	acceptor_gain	0.9800
6:26504924:G:GG	acceptor_gain	0.9800
6:26504924:GCTCT:G	acceptor_gain	0.9800
6:26505202:ACCAG:A	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000092679 (6:26503844 G>C), RS1000264076 (6:26504260 G>C,T), RS1000971796 (6:26509547 A>C), RS1001237209 (6:26505853 T>C), RS1001266921 (6:26506156 A>G), RS1001500649 (6:26502114 C>T), RS1001613720 (6:26498559 T>C), RS1001807520 (6:26505584 C>G), RS1002156712 (6:26506021 A>C), RS1002218235 (6:26500265 C>T), RS1002243035 (6:26507496 T>C), RS1002593695 (6:26499829 G>A), RS1003194323 (6:26507186 A>G), RS1003323249 (6:26499256 A>G), RS1003605133 (6:26499509 T>C,G)

Disease associations

OMIM: gene MIM:601610 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000301_8	Iron status biomarkers	6.000000e-08
GCST004521_113	Autism spectrum disorder or schizophrenia	3.000000e-19
GCST004521_208	Autism spectrum disorder or schizophrenia	5.000000e-17
GCST004521_215	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_301	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST004521_69	Autism spectrum disorder or schizophrenia	8.000000e-24
GCST005316_551	Intelligence (MTAG)	2.000000e-11
GCST005316_563	Intelligence (MTAG)	8.000000e-13
GCST005316_627	Intelligence (MTAG)	1.000000e-14
GCST007335_33	Age at first sexual intercourse	2.000000e-07
GCST008152_157	Weight	6.000000e-06
GCST008158_7	Body mass index	5.000000e-07
GCST008396_3	Educational attainment (years of education)	2.000000e-08
GCST008832_6	Gastroesophageal reflux disease	1.000000e-10
GCST010002_50	Refractive error	4.000000e-34
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010142_74	Fish- and plant-related diet	9.000000e-09
GCST010142_82	Fish- and plant-related diet	3.000000e-08
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST90000514_4	Gastroesophageal reflux disease	2.000000e-13
GCST90016674_6	Liver iron content	1.000000e-38
GCST90020028_819	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004461	iron biomarker measurement
EFO:0004337	intelligence
EFO:0009749	age at first sexual intercourse measurement
EFO:0004338	body weight
EFO:0004340	body mass index
EFO:0004784	self reported educational attainment
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment	1
glycidyl methacrylate	decreases expression	1
arsenite	increases methylation	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Arsenic	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1SG	HAP1 BTN1A1 (-) 1	Cancer cell line	Male
CVCL_E1SH	HAP1 BTN1A1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.