BIN2

Summary

BIN2 (bridging integrator 2, HGNC:1053) is a protein-coding gene on chromosome 12q13.13, encoding Bridging integrator 2 (Q9UBW5). Promotes cell motility and migration, probably via its interaction with the cell membrane and with podosome proteins that mediate interaction with the cytoskeleton.

Enables phospholipid binding activity. Involved in several processes, including phagocytosis, engulfment; plasma membrane tubulation; and podosome assembly. Located in phagocytic cup and podosome.

Source: NCBI Gene 51411 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 75 total
• MANE Select transcript: NM_016293

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1053
Approved symbol	BIN2
Name	bridging integrator 2
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	BRAP-1
Ensembl gene	ENSG00000110934
Ensembl biotype	protein_coding
OMIM	605936
Entrez	51411

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000452142, ENST00000544402, ENST00000603177, ENST00000603260, ENST00000604560, ENST00000604702, ENST00000605039, ENST00000605423, ENST00000605819, ENST00000615107, ENST00000871152, ENST00000871153, ENST00000871154, ENST00000871155, ENST00000871156, ENST00000871157, ENST00000871158

RefSeq mRNA: 7 — MANE Select: NM_016293 NM_001290007, NM_001290008, NM_001290009, NM_001364779, NM_001364780, NM_001364781, NM_016293

CCDS: CCDS76561, CCDS8811, CCDS91696

Canonical transcript exons

ENST00000615107 — 13 exons

Exon	Start	End
ENSE00000938786	51302020	51302115
ENSE00001286152	51302686	51302780
ENSE00003467328	51281038	51281528
ENSE00003490135	51295796	51295878
ENSE00003496396	51284716	51284787
ENSE00003575341	51299607	51299714
ENSE00003578773	51297089	51297164
ENSE00003592163	51313823	51313903
ENSE00003619259	51288108	51288188
ENSE00003646967	51303087	51303141
ENSE00003651812	51291591	51292344
ENSE00003671952	51299203	51299288
ENSE00003845857	51324022	51324174

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 99.26.

FANTOM5 (CAGE): breadth broad, TPM avg 13.8701 / max 417.4465, expressed in 491 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130955	8.6182	425
130956	1.8047	368
130957	1.6972	366
130954	1.4492	171
130958	0.2297	141
130959	0.0712	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.26	gold quality
monocyte	CL:0000576	99.07	gold quality
mononuclear cell	CL:0000842	99.01	gold quality
leukocyte	CL:0000738	99.00	gold quality
blood	UBERON:0000178	98.18	gold quality
bone marrow cell	CL:0002092	97.02	gold quality
bone marrow	UBERON:0002371	95.66	gold quality
spleen	UBERON:0002106	95.35	gold quality
trabecular bone tissue	UBERON:0002483	93.59	gold quality
lymph node	UBERON:0000029	93.22	gold quality
vermiform appendix	UBERON:0001154	93.10	gold quality
caecum	UBERON:0001153	90.34	gold quality
right lung	UBERON:0002167	89.26	gold quality
upper lobe of left lung	UBERON:0008952	86.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.07	gold quality
superficial temporal artery	UBERON:0001614	85.99	gold quality
upper lobe of lung	UBERON:0008948	85.95	gold quality
epithelium of nasopharynx	UBERON:0001951	85.56	silver quality
placenta	UBERON:0001987	85.15	gold quality
decidua	UBERON:0002450	84.00	gold quality
rectum	UBERON:0001052	83.68	gold quality
diaphragm	UBERON:0001103	83.60	gold quality
gall bladder	UBERON:0002110	83.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.59	gold quality
colonic epithelium	UBERON:0000397	82.42	gold quality
lung	UBERON:0002048	82.23	gold quality
tonsil	UBERON:0002372	82.13	gold quality
mucosa of transverse colon	UBERON:0004991	82.00	gold quality
thymus	UBERON:0002370	81.70	gold quality
triceps brachii	UBERON:0001509	81.06	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	96.96
E-HCAD-4	yes	85.20
E-CURD-122	yes	47.90
E-MTAB-6701	yes	37.91
E-CURD-112	yes	36.28
E-HCAD-10	yes	25.49
E-HCAD-6	yes	24.09
E-HCAD-9	yes	17.22
E-MTAB-10553	yes	12.88
E-MTAB-6678	yes	12.11
E-MTAB-9067	yes	11.90
E-GEOD-130148	yes	4.44
E-MTAB-9801	yes	4.35
E-MTAB-7606	no	1023.89
E-GEOD-100618	no	778.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting BIN2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-2276-5P	96.27	65.85	937

Literature-anchored findings (GeneRIF, showing 3)

• Bin2 is a BAR domain adapter protein structurally related but functionally distinct from family members Bin1 and amphiphysin. (PMID:10903846)
• Bin2 is a membrane-sculpting protein that influences podosome formation, motility and phagocytosis in leucocytes. (PMID:23285027)
• Inhibition of BIN2 extends reproductive lifespan. (PMID:37118339)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bin2a	ENSDARG00000003219
danio_rerio	bin2b	ENSDARG00000010255
mus_musculus	Bin2	ENSMUSG00000098112
rattus_norvegicus	Bin2	ENSRNOG00000031930
drosophila_melanogaster	Amph	FBGN0027356

Paralogs (3): AMPH (ENSG00000078053), BIN1 (ENSG00000136717), BIN3 (ENSG00000147439)

Protein

Protein identifiers

Bridging integrator 2 — Q9UBW5 (reviewed: Q9UBW5)

Alternative names: Breast cancer-associated protein 1

All UniProt accessions (3): Q9UBW5, S4R3J0, S4R418

UniProt curated annotations — full annotation on UniProt →

Function. Promotes cell motility and migration, probably via its interaction with the cell membrane and with podosome proteins that mediate interaction with the cytoskeleton. Modulates membrane curvature and mediates membrane tubulation. Plays a role in podosome formation. Inhibits phagocytosis.

Subunit / interactions. Homodimer. Interacts with BIN1. Interacts with ARHGEF6 (via SH3 domain), ARHGEF7 (via SH3 domain), SH3GL1, SH3GL2 and SH3GL3. Identified in a complex with ARHGEF6 and GIT2.

Subcellular location. Cytoplasm. Cell projection. Podosome membrane. Cell cortex. Phagocytic cup.

Tissue specificity. Detected in natural killer cells (at protein level). Highest level expression seen in spleen and peripheral blood leukocytes and is also expressed at high levels in thymus, colon and placenta, suggesting preferential expression in hematopoietic tissues.

Domain organisation. The BAR domain mediates dimerization and interaction with membranes enriched in phosphatidylinositides.

Induction. Up-regulated during monocytic differentiation.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UBW5-1	1	yes
Q9UBW5-2	2
Q9UBW5-3	3

RefSeq proteins (7): NP_001276936, NP_001276937, NP_001276938, NP_001351708, NP_001351709, NP_001351710, NP_057377* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003005	Amphiphysin	Family
IPR004148	BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR046984	BAR_Bin2	Domain
IPR048886	Bin2_C	Domain

Pfam: PF03114, PF21532

UniProt features (42 total): modified residue 12, compositionally biased region 9, helix 7, mutagenesis site 4, splice variant 2, sequence variant 2, chain 1, domain 1, region of interest 1, coiled-coil region 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4AVM	X-RAY DIFFRACTION	1.91
4I1Q	X-RAY DIFFRACTION	2.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBW5-F1	66.40	0.39

Functional residue map

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

Post-translational modifications (12): 273, 357, 383, 395, 436, 438, 440, 444, 447, 451, 458, 462

Mutagenesis-validated functional residues (4):

Position	Phenotype
13	strongly reduces binding to membranes.
21	strongly reduces binding to membranes.
81	abolishes dimerization and membrane binding; when associated with e-214.
214	abolishes dimerization and membrane binding; when associated with r-81.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9673768	Signaling by membrane-tethered fusions of PDGFRA or PDGFRB
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-9671555	Signaling by PDGFR in disease

MSigDB gene sets: 177 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_CELL_CHEMOTAXIS, GNF2_CASP8, GOCC_SECRETORY_GRANULE, CHUNG_BLISTER_CYTOTOXICITY_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_TAXIS, MODULE_301, GOBP_ORGANELLE_ASSEMBLY, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GNF2_CD97, BILBAN_B_CLL_LPL_DN, GOBP_MEMBRANE_ORGANIZATION, GNF2_PTPRC

GO Biological Process (4): phagocytosis, engulfment (GO:0006911), cell chemotaxis (GO:0060326), podosome assembly (GO:0071800), plasma membrane tubulation (GO:0097320)

GO Molecular Function (2): phospholipid binding (GO:0005543), protein binding (GO:0005515)

GO Cellular Component (11): phagocytic cup (GO:0001891), podosome (GO:0002102), extracellular region (GO:0005576), plasma membrane (GO:0005886), cell cortex (GO:0005938), secretory granule lumen (GO:0034774), cell projection (GO:0042995), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	1
Signaling by PDGFR in disease	1
Immune System	1
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell periphery	2
phagocytosis	1
plasma membrane invagination	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
protein-containing complex assembly	1
plasma membrane bounded cell projection assembly	1
plasma membrane organization	1
lipid binding	1
binding	1
plasma membrane	1
actin-based cell projection	1
membrane	1
cytoplasm	1
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BIN2	BIN3	Q9NQY0	990
BIN2	BIN1	O00499	633
BIN2	SLC35G1	Q2M3R5	509
BIN2	RBBP8	Q99708	437
BIN2	MDC1	Q14676	430
BIN2	RNF168	Q8IYW5	418
BIN2	PACRG	Q96M98	418
BIN2	MYC	P01106	403
BIN2	SNX9	Q9Y5X1	394
BIN2	PSTPIP1	O43586	367
BIN2	CIBAR2	Q6ZTR7	362
BIN2	FCHSD1	Q86WN1	359
BIN2	SNX33	Q8WV41	357
BIN2	A0A087WZY1	A0A087WZY1	350
BIN2	NME9	Q86XW9	349

IntAct

19 interactions, top by confidence:

A	B	Type	Score
KIF1B	YWHAZ	psi-mi:“MI:0914”(association)	0.740
BIN2	BIN1	psi-mi:“MI:0915”(physical association)	0.640
BIN1	BIN2	psi-mi:“MI:0915”(physical association)	0.640
BIN2	BIN1	psi-mi:“MI:0914”(association)	0.640
APPBP2	BIN2	psi-mi:“MI:0915”(physical association)	0.560
TERF1	BIN2	psi-mi:“MI:0915”(physical association)	0.370
TINF2	BIN2	psi-mi:“MI:0915”(physical association)	0.370
POT1	BIN2	psi-mi:“MI:0915”(physical association)	0.370
EFEMP1	ZNF316	psi-mi:“MI:0914”(association)	0.350
BIN2	BIN1	psi-mi:“MI:0914”(association)	0.350
KIF1B	PLOD1	psi-mi:“MI:0914”(association)	0.350
BIN2	APPBP2	psi-mi:“MI:0915”(physical association)	0.000
clpB	BIN2	psi-mi:“MI:0915”(physical association)	0.000
BIN2	clpB	psi-mi:“MI:0915”(physical association)	0.000
BIN2	ptsA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): BIN1 (Affinity Capture-MS), AMPH (Affinity Capture-MS), BIN2 (Affinity Capture-MS), BIN2 (Affinity Capture-MS), BIN2 (Two-hybrid), BIN1 (Affinity Capture-MS), AMPH (Affinity Capture-MS), BIN2 (Affinity Capture-MS), BIN2 (Affinity Capture-MS), BIN2 (Affinity Capture-Western), HIST1H3A (Cross-Linking-MS (XL-MS)), BIN2 (Protein-peptide), BIN2 (Cross-Linking-MS (XL-MS)), BIN2 (Two-hybrid), BIN2 (Two-hybrid)

ESM2 similar proteins: A2A791, A2YEZ6, A3BDI8, B5DF11, E6ZGB4, O15164, O75151, O75376, O76080, O88878, O88974, P49140, P55265, Q02395, Q08BR4, Q15047, Q15054, Q3SZY7, Q3UWM4, Q4KKX4, Q4V7W5, Q56R14, Q5JSH3, Q5R7S6, Q5U2T3, Q5VZL5, Q5ZK28, Q60974, Q64127, Q6DGF4, Q6FIF0, Q6INA9, Q6P949, Q6PFK1, Q6ZMT4, Q80TJ7, Q86XZ4, Q8CGC4, Q8K1N4, Q8QG78

Diamond homologs: D3Z6Q9, O00499, O08539, O08838, O08839, P49418, P50478, Q5ZKL7, Q68FR2, Q7TQF7, Q9UBW5, Q95UN8, Q5AFE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2316 predictions. Top by Δscore:

Variant	Effect	Δscore
12:51281527:ACC:A	acceptor_loss	1.0000
12:51284710:TCTTA:T	donor_loss	1.0000
12:51284711:CTTAC:C	donor_loss	1.0000
12:51284712:TTAC:T	donor_loss	1.0000
12:51284713:TACCT:T	donor_loss	1.0000
12:51284714:A:AC	donor_gain	1.0000
12:51284715:C:CC	donor_gain	1.0000
12:51284715:C:T	donor_loss	1.0000
12:51284715:CCT:C	donor_gain	1.0000
12:51284788:C:CC	acceptor_gain	1.0000
12:51288095:AGG:A	donor_gain	1.0000
12:51288096:G:C	donor_gain	1.0000
12:51288109:T:TA	donor_gain	1.0000
12:51288121:G:C	donor_gain	1.0000
12:51288135:ATTAT:A	donor_gain	1.0000
12:51288138:AT:A	donor_gain	1.0000
12:51295790:GCTCA:G	donor_loss	1.0000
12:51295791:CTCAC:C	donor_loss	1.0000
12:51295792:TCA:T	donor_loss	1.0000
12:51295793:CACCT:C	donor_loss	1.0000
12:51295794:A:C	donor_loss	1.0000
12:51295795:C:CG	donor_loss	1.0000
12:51295874:TTCAG:T	acceptor_gain	1.0000
12:51295875:TCAG:T	acceptor_gain	1.0000
12:51295876:CAG:C	acceptor_gain	1.0000
12:51295876:CAGC:C	acceptor_gain	1.0000
12:51295879:C:CC	acceptor_gain	1.0000
12:51295886:CAA:C	acceptor_gain	1.0000
12:51295887:A:T	acceptor_gain	1.0000
12:51299285:CTGC:C	acceptor_gain	1.0000

AlphaMissense

3700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:51299233:A:G	L191P	0.999
12:51299665:C:G	R153P	0.999
12:51299688:T:A	K145N	0.999
12:51299688:T:G	K145N	0.999
12:51299690:T:C	K145E	0.999
12:51303113:A:G	L64P	0.999
12:51299221:A:G	L195P	0.998
12:51299669:C:G	A152P	0.998
12:51299686:A:G	L146P	0.998
12:51299692:C:G	R144P	0.998
12:51299698:C:G	R142P	0.998
12:51302721:A:G	W93R	0.998
12:51302721:A:T	W93R	0.998
12:51297107:G:C	F220L	0.997
12:51297107:G:T	F220L	0.997
12:51297109:A:G	F220L	0.997
12:51299253:A:C	F184L	0.997
12:51299253:A:T	F184L	0.997
12:51299255:A:G	F184L	0.997
12:51299663:G:C	H154D	0.997
12:51299674:T:G	D150A	0.997
12:51299700:C:A	K141N	0.997
12:51299700:C:G	K141N	0.997
12:51303125:A:G	L60P	0.997
12:51324034:C:A	R23S	0.997
12:51324034:C:G	R23S	0.997
12:51299656:A:G	L156P	0.996
12:51299674:T:A	D150V	0.996
12:51299674:T:C	D150G	0.996
12:51299675:C:G	D150H	0.996

dbSNP variants (sampled 300 via entrez): RS1000101899 (12:51281727 A>G), RS1000130252 (12:51323684 A>C), RS1000134515 (12:51281237 T>A), RS1000143285 (12:51292421 G>A), RS1000159138 (12:51322837 T>C,G), RS1000200793 (12:51322286 T>C), RS1000246028 (12:51317438 C>G,T), RS1000247542 (12:51286695 C>T), RS1000382492 (12:51287966 T>G), RS1000457983 (12:51316358 T>G), RS1000463565 (12:51323108 A>C,G), RS1000497833 (12:51324327 T>A), RS1000502414 (12:51323357 C>T), RS1000529304 (12:51318458 C>T), RS1000558963 (12:51318662 G>A)

Disease associations

OMIM: gene MIM:605936 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001167_1	Aging (time to death)	2.000000e-06
GCST004599_188	Mean platelet volume	9.000000e-27
GCST90002379_100	Basophil count	8.000000e-30
GCST90002380_106	Basophil percentage of white cells	3.000000e-25
GCST90002395_129	Mean platelet volume	3.000000e-22
GCST90002402_378	Platelet count	4.000000e-20

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0022597	aging
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sulforaphane	increases expression	1
abrine	decreases expression	1
trametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Cisplatin	increases expression	1
Cytarabine	increases expression	1
Diuron	decreases expression	1
Estradiol	decreases expression	1
Nickel	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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