BTNL9

Summary

BTNL9 (butyrophilin like 9, HGNC:24176) is a protein-coding gene on chromosome 5q35.3, encoding Butyrophilin-like protein 9 (Q6UXG8).

Predicted to enable signaling receptor binding activity. Predicted to be involved in T cell receptor signaling pathway and regulation of cytokine production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane.

Source: NCBI Gene 153579 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 136 total
• MANE Select transcript: NM_152547

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24176
Approved symbol	BTNL9
Name	butyrophilin like 9
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32535, BTN8
Ensembl gene	ENSG00000165810
Ensembl biotype	protein_coding
OMIM	620648
Entrez	153579

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000327705, ENST00000376841, ENST00000491209, ENST00000506782, ENST00000509395, ENST00000511056, ENST00000511589, ENST00000512570, ENST00000513424, ENST00000515271, ENST00000864439, ENST00000864440, ENST00000864441, ENST00000864442, ENST00000864443, ENST00000864444, ENST00000864445, ENST00000864446, ENST00000969776, ENST00000969777, ENST00000969778

RefSeq mRNA: 2 — MANE Select: NM_152547 NM_001308245, NM_152547

CCDS: CCDS4460, CCDS78104

Canonical transcript exons

ENST00000327705 — 11 exons

Exon	Start	End
ENSE00001096827	181050088	181050369
ENSE00001314486	181055989	181056015
ENSE00001421113	181055433	181055453
ENSE00001869430	181040266	181040432
ENSE00001955787	181059237	181061521
ENSE00003461174	181053200	181053316
ENSE00003505005	181045467	181045598
ENSE00003545414	181054239	181054259
ENSE00003585391	181047927	181048271
ENSE00003605514	181053469	181053501
ENSE00003607707	181058352	181058378

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 99.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7787 / max 305.4297, expressed in 1102 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60676	2.6197	913
60678	1.3166	365
60674	0.8499	115
60673	0.4776	116
60675	0.2445	71
60677	0.1585	91
60679	0.1118	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.25	gold quality
omental fat pad	UBERON:0010414	99.25	gold quality
peritoneum	UBERON:0002358	99.22	gold quality
apex of heart	UBERON:0002098	98.97	gold quality
right uterine tube	UBERON:0001302	98.93	gold quality
adipose tissue	UBERON:0001013	98.91	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.76	gold quality
spleen	UBERON:0002106	97.21	gold quality
upper lobe of left lung	UBERON:0008952	97.12	gold quality
heart left ventricle	UBERON:0002084	97.09	gold quality
upper lobe of lung	UBERON:0008948	97.09	gold quality
cardiac ventricle	UBERON:0002082	96.89	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.37	gold quality
mucosa of stomach	UBERON:0001199	95.68	gold quality
sural nerve	UBERON:0015488	95.17	gold quality
right lobe of thyroid gland	UBERON:0001119	95.04	gold quality
left lobe of thyroid gland	UBERON:0001120	94.99	gold quality
right atrium auricular region	UBERON:0006631	94.90	gold quality
lung	UBERON:0002048	94.59	gold quality
lower lobe of lung	UBERON:0008949	94.55	gold quality
skin of hip	UBERON:0001554	94.54	gold quality
cardiac atrium	UBERON:0002081	94.37	gold quality
gastrocnemius	UBERON:0001388	94.24	gold quality
heart	UBERON:0000948	94.15	gold quality
thyroid gland	UBERON:0002046	94.04	gold quality
muscle of leg	UBERON:0001383	93.81	gold quality
parietal pleura	UBERON:0002400	93.26	gold quality
vena cava	UBERON:0004087	93.26	gold quality
metanephros cortex	UBERON:0010533	92.98	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	2492.08
E-GEOD-135922	yes	34.86
E-MTAB-9067	yes	6.67
E-MTAB-10137	yes	4.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting BTNL9, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-875-3P	99.63	69.47	2548

Literature-anchored findings (GeneRIF, showing 5)

• Authors investigated the function of BTNL9 in UM proliferation and invasion. BTNL9 mRNAs in adjacent tissues were remarkably higher than in UM tissues. The percentages of BTNL9 low expression and high expression were 56.45% and 43.55%, respectively. (PMID:31039142)
• BTNL9 is frequently downregulated and inhibits proliferation and metastasis via the P53/CDC25C and P53/GADD45 pathways in breast cancer. (PMID:33756341)
• Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis. (PMID:35015148)
• A stop-gain variant in BTNL9 is associated with atherogenic lipid profiles. (PMID:36340932)
• LncRNA CALML3-AS1 modulated by m[6]A modification induces BTNL9 methylation to drive non-small-cell lung cancer progression. (PMID:37884580)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Btnl9	ENSMUSG00000040283
rattus_norvegicus	Btnl9	ENSRNOG00000046377

Paralogs (15): BTN3A1 (ENSG00000026950), CD276 (ENSG00000103855), BTN3A3 (ENSG00000111801), BTN2A1 (ENSG00000112763), BTNL8 (ENSG00000113303), HHLA2 (ENSG00000114455), BTN2A2 (ENSG00000124508), BTN1A1 (ENSG00000124557), VTCN1 (ENSG00000134258), ICOSLG (ENSG00000160223), ERMAP (ENSG00000164010), BTNL3 (ENSG00000168903), BTN3A2 (ENSG00000186470), BTNL2 (ENSG00000204290), MOG (ENSG00000204655)

Protein

Protein identifiers

Butyrophilin-like protein 9 — Q6UXG8 (reviewed: Q6UXG8)

All UniProt accessions (3): A0A1S5UZ21, B7Z4Y8, Q6UXG8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q6UXG8-1	1	yes
Q6UXG8-2	2
Q6UXG8-3	3

RefSeq proteins (2): NP_001295174, NP_689760* (*=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
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 (18 total): splice variant 4, glycosylation site 3, topological domain 2, domain 2, signal peptide 1, chain 1, disulfide bond 1, sequence variant 1, transmembrane region 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXG8-F1	84.28	0.62

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 (1): 59–133

Glycosylation sites (3): 139, 224, 102

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: 116 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_CYTOKINE_PRODUCTION, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY, CHIANG_LIVER_CANCER_SUBCLASS_INTERFERON_DN, CUI_TCF21_TARGETS_2_DN, GOMF_SIGNALING_RECEPTOR_BINDING, CHANDRAN_METASTASIS_UP, GOCC_SIDE_OF_MEMBRANE, GEORGES_TARGETS_OF_MIR192_AND_MIR215, MIKKELSEN_MEF_LCP_WITH_H3K27ME3

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

GO Molecular Function (2): signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), 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
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
antigen receptor-mediated signaling pathway	1
protein binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

752 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTNL9	XDH	P47989	988
BTNL9	PLIN2	Q99541	956
BTNL9	MFGE8	Q08431	772
BTNL9	MUC1	P13931	583
BTNL9	LTF	P02788	568
BTNL9	GOT2	P00505	542
BTNL9	CD8A	P01732	509
BTNL9	CIDEA	O60543	508
BTNL9	MUC15	Q8N387	498
BTNL9	AASDH	Q4L235	458
BTNL9	CD1B	P29016	452
BTNL9	PLIN1	O60240	443
BTNL9	BTN2A1	P78408	443
BTNL9	OMG	P23515	437
BTNL9	LALBA	P00709	431

IntAct

5 interactions, top by confidence:

A	B	Type	Score
BTNL9	LRFN5	psi-mi:“MI:0915”(physical association)	0.400
IL6R	BTNL9	psi-mi:“MI:0915”(physical association)	0.400
BTNL9	GPR89A	psi-mi:“MI:0914”(association)	0.350
BTNL9	TNPO2	psi-mi:“MI:0914”(association)	0.350

BioGRID (154): BTNL9 (Two-hybrid), BTNL9 (Two-hybrid), BTNL9 (Two-hybrid), BTNL9 (Two-hybrid), BTNL9 (Two-hybrid), JAGN1 (Two-hybrid), NINJ2 (Two-hybrid), RPRM (Two-hybrid), ADIPOQ (Two-hybrid), EDDM3A (Two-hybrid), MFSD5 (Two-hybrid), GIMAP5 (Two-hybrid), SYS1 (Two-hybrid), PPAPDC2 (Two-hybrid), TNF (Two-hybrid)

ESM2 similar proteins: A0A0E4BZH1, A4QPC6, A7TZE6, A8K4G0, A8MVZ5, O00478, O00481, O00635, O70355, O75677, O75679, P14373, P18892, P19474, P55803, P78410, Q13410, Q1XHU0, Q3ZEE5, Q58DK8, Q5BN31, Q5C8U1, Q5D7H8, Q5D7I0, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7J2, Q5R7W8, Q5R996, Q61885, Q62158, Q62191, Q62556, Q6MFZ5, Q6MG97, Q6UX41, Q6UXE8, Q6UXG8, Q7KYR7

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	6
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

1427 predictions. Top by Δscore:

Variant	Effect	Δscore
5:181055977:T:TA	acceptor_gain	1.0000
5:181040430:CAGGT:C	donor_loss	0.9900
5:181040431:AGG:A	donor_loss	0.9900
5:181040433:G:GA	donor_loss	0.9900
5:181040434:T:A	donor_loss	0.9900
5:181059235:A:AG	acceptor_gain	0.9900
5:181059236:G:GG	acceptor_gain	0.9900
5:181047925:A:AG	acceptor_gain	0.9800
5:181047925:AGAGG:A	acceptor_gain	0.9800
5:181047926:G:GG	acceptor_gain	0.9800
5:181048262:G:GT	donor_gain	0.9800
5:181048267:AGCAG:A	donor_loss	0.9800
5:181048268:GCAGG:G	donor_loss	0.9800
5:181048269:CAGGT:C	donor_loss	0.9800
5:181048271:GGTG:G	donor_loss	0.9800
5:181048272:G:GA	donor_loss	0.9800
5:181048273:T:A	donor_loss	0.9800
5:181053312:CCGAG:C	donor_loss	0.9800
5:181053313:CGAG:C	donor_loss	0.9800
5:181053314:GAGG:G	donor_loss	0.9800
5:181053315:AGG:A	donor_loss	0.9800
5:181053316:GG:G	donor_loss	0.9800
5:181053318:T:G	donor_loss	0.9800
5:181040428:GCCAG:G	donor_gain	0.9700
5:181040433:G:GG	donor_gain	0.9700
5:181047924:TAGAG:T	acceptor_gain	0.9700
5:181053297:G:GT	donor_gain	0.9700
5:181059235:AGTG:A	acceptor_gain	0.9700
5:181059236:GTGG:G	acceptor_gain	0.9700
5:181059236:GT:G	acceptor_gain	0.9600

AlphaMissense

3452 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:181059377:A:C	S375R	0.992
5:181059379:C:A	S375R	0.992
5:181059379:C:G	S375R	0.992
5:181059412:G:C	W386C	0.991
5:181059412:G:T	W386C	0.991
5:181059440:T:A	W396R	0.989
5:181059440:T:C	W396R	0.989
5:181059646:C:A	N464K	0.988
5:181059646:C:G	N464K	0.988
5:181048037:T:A	W74R	0.987
5:181048037:T:C	W74R	0.987
5:181059545:T:C	F431L	0.986
5:181059547:C:A	F431L	0.986
5:181059547:C:G	F431L	0.986
5:181059707:T:G	Y485D	0.985
5:181059639:T:C	F462S	0.984
5:181059711:T:C	F486S	0.982
5:181059410:T:A	W386R	0.981
5:181059410:T:C	W386R	0.981
5:181048040:T:C	F75L	0.980
5:181048042:C:A	F75L	0.980
5:181048042:C:G	F75L	0.980
5:181050165:T:A	W178R	0.979
5:181050165:T:C	W178R	0.979
5:181059353:T:C	F367L	0.979
5:181059355:C:A	F367L	0.979
5:181059355:C:G	F367L	0.979
5:181059407:T:G	Y385D	0.979
5:181059638:T:C	F462L	0.979
5:181059640:C:A	F462L	0.979

dbSNP variants (sampled 300 via entrez): RS1000121361 (5:181056970 GATGGCTGTCTTTT>G), RS1000152719 (5:181061726 CCTT>C), RS1000204587 (5:181061478 A>G,T), RS1000546643 (5:181056519 T>G), RS1000552160 (5:181050555 A>G), RS1001137939 (5:181045317 C>T), RS1001189537 (5:181056270 A>G,T), RS1001246274 (5:181060871 C>T), RS1001469343 (5:181048828 T>A), RS1001562520 (5:181049084 G>A,C), RS1001705879 (5:181047416 T>A), RS1001716927 (5:181061005 C>T), RS1001792728 (5:181055127 T>G), RS1001833181 (5:181040881 C>G,T), RS1001865897 (5:181038683 G>A,T)

Disease associations

OMIM: gene MIM:620648 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_2056	Metabolite levels	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010345	cholesteryl ester 18:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases mutagenesis, affects methylation	2
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
DEET	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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