BIN3

Summary

BIN3 (bridging integrator 3, HGNC:1054) is a protein-coding gene on chromosome 8p21.3, encoding Bridging integrator 3 (Q9NQY0). Involved in cytokinesis and septation where it has a role in the localization of F-actin.

The product of this gene is a member of the BAR domain protein family. The encoded protein is comprised solely of a BAR domain which is predicted to form coiled-coil structures and proposed to mediate dimerization, sense and induce membrane curvature, and bind small GTPases. BAR domain proteins have been implicated in endocytosis, intracellular transport, and a diverse set of other processes.

Source: NCBI Gene 55909 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 93 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_018688

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1054
Approved symbol	BIN3
Name	bridging integrator 3
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147439
Ensembl biotype	protein_coding
OMIM	606396
Entrez	55909

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000276416, ENST00000399977, ENST00000518366, ENST00000519335, ENST00000519513, ENST00000519863, ENST00000520292, ENST00000520489, ENST00000521140, ENST00000522268, ENST00000522687, ENST00000853250, ENST00000939253

RefSeq mRNA: 2 — MANE Select: NM_018688 NM_001363046, NM_018688

CCDS: CCDS47825

Canonical transcript exons

ENST00000276416 — 9 exons

Exon	Start	End
ENSE00002138851	22669044	22669121
ENSE00002139181	22620418	22621568
ENSE00003465291	22636525	22636586
ENSE00003478789	22630442	22630578
ENSE00003494397	22636922	22636962
ENSE00003522391	22629964	22630004
ENSE00003555692	22644755	22644803
ENSE00003562675	22624222	22624363
ENSE00003611306	22623915	22624049

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 97.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6109 / max 862.7390, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92237	19.6533	1815
92236	0.9576	227

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.64	gold quality
right adrenal gland cortex	UBERON:0035827	93.44	gold quality
right adrenal gland	UBERON:0001233	93.04	gold quality
left adrenal gland	UBERON:0001234	93.01	gold quality
left adrenal gland cortex	UBERON:0035825	93.01	gold quality
adrenal cortex	UBERON:0001235	92.56	gold quality
oocyte	CL:0000023	92.55	gold quality
adrenal gland	UBERON:0002369	92.36	gold quality
blood	UBERON:0000178	92.29	gold quality
right uterine tube	UBERON:0001302	91.93	gold quality
lower esophagus mucosa	UBERON:0035834	91.81	gold quality
tibial nerve	UBERON:0001323	91.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.46	gold quality
granulocyte	CL:0000094	91.25	gold quality
stromal cell of endometrium	CL:0002255	90.92	gold quality
monocyte	CL:0000576	89.96	gold quality
leukocyte	CL:0000738	89.93	gold quality
gall bladder	UBERON:0002110	89.84	gold quality
mononuclear cell	CL:0000842	89.82	gold quality
adrenal tissue	UBERON:0018303	89.73	gold quality
omental fat pad	UBERON:0010414	89.63	gold quality
peritoneum	UBERON:0002358	89.60	gold quality
skin of leg	UBERON:0001511	89.59	gold quality
mucosa of transverse colon	UBERON:0004991	89.45	gold quality
ascending aorta	UBERON:0001496	89.44	gold quality
thoracic aorta	UBERON:0001515	89.38	gold quality
popliteal artery	UBERON:0002250	89.29	gold quality
tibial artery	UBERON:0007610	89.29	gold quality
aorta	UBERON:0000947	89.26	gold quality
left coronary artery	UBERON:0001626	89.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	239.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• BIN3 is a BAR domain adapter protein implicated in actin regulation; it is homologous to budding yeast Rvs161 and fission yeast Hob3. (PMID:11274158)
• like RVS161, hob3+ and BIN3 regulate F-actin localization, but other roles for these genes have diverged somewhat during evolution (PMID:11274158)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bin3	ENSDARG00000099651
mus_musculus	Bin3	ENSMUSG00000022089
rattus_norvegicus	Bin3	ENSRNOG00000018023
caenorhabditis_elegans		WBGENE00010272

Paralogs (3): AMPH (ENSG00000078053), BIN2 (ENSG00000110934), BIN1 (ENSG00000136717)

Protein

Protein identifiers

Bridging integrator 3 — Q9NQY0 (reviewed: Q9NQY0)

All UniProt accessions (5): Q9NQY0, E5RGB5, E5RHU4, E5RJI6, H7BYV6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in cytokinesis and septation where it has a role in the localization of F-actin.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Ubiquitously expressed except in brain.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQY0-1	1	yes
Q9NQY0-2	2

RefSeq proteins (2): NP_001349975, NP_061158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004148	BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR037428	Bin3_BAR	Domain
IPR046982	BIN3/RVS161-like	Family

Pfam: PF03114

UniProt features (9 total): coiled-coil region 3, chain 1, domain 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQY0-F1	92.83	0.85

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 184 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, CGGAARNGGCNG_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_GROWTH, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGENERATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_LAMELLIPODIUM_ASSEMBLY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (13): endocytosis (GO:0006897), actin filament organization (GO:0007015), intracellular protein localization (GO:0008104), unidimensional cell growth (GO:0009826), regulation of lamellipodium assembly (GO:0010591), myoblast migration involved in skeletal muscle regeneration (GO:0014839), skeletal muscle fiber development (GO:0048741), actin cortical patch localization (GO:0051666), cytoskeleton-dependent cytokinesis (GO:0061640), plasma membrane tubulation (GO:0097320), skeletal muscle tissue regeneration (GO:0043403), developmental growth (GO:0048589), cell division (GO:0051301)

GO Molecular Function (3): cytoskeletal adaptor activity (GO:0008093), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (3): cytoplasm (GO:0005737), actin cytoskeleton (GO:0015629), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
macromolecule localization	1
cell morphogenesis	1
cell growth	1
developmental growth involved in morphogenesis	1
lamellipodium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of lamellipodium organization	1
skeletal muscle tissue regeneration	1
myoblast migration	1
skeletal muscle tissue development	1
myotube cell development	1
cellular localization	1
cytokinesis	1
plasma membrane organization	1
tissue regeneration	1
developmental process	1
growth	1
cellular process	1
cytoskeletal protein binding	1
protein-macromolecule adaptor activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoskeleton	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BIN3	BIN2	Q9UBW5	990
BIN3	BIN1	O00499	941
BIN3	MEPCE	Q7L2J0	921
BIN3	CDK9	P50750	692
BIN3	HEXIM1	O94992	653
BIN3	LARP7	Q4G0J3	574
BIN3	BCDIN3D	Q7Z5W3	568
BIN3	SART3	Q15020	542
BIN3	JADE3	Q92613	508
BIN3	DNM2	P50570	478
BIN3	DACT2	Q5SW24	457
BIN3	HMG20B	Q9P0W2	451
BIN3	C8orf58	Q8NAV2	419
BIN3	SPTB	P11277	394
BIN3	DNMBP	Q6XZF7	376

IntAct

60 interactions, top by confidence:

A	B	Type	Score
DNMBP	BIN3	psi-mi:“MI:0915”(physical association)	0.790
BIN3	DNMBP	psi-mi:“MI:0915”(physical association)	0.790
SNX1	SNX2	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
POLR1C	BIN3	psi-mi:“MI:0915”(physical association)	0.560
BIN3	C14orf119	psi-mi:“MI:0915”(physical association)	0.560
TRIM69	BIN3	psi-mi:“MI:0915”(physical association)	0.560
BIN3	NXF1	psi-mi:“MI:0915”(physical association)	0.560
UBL5	BIN3	psi-mi:“MI:0915”(physical association)	0.560
RPRD1B	BIN3	psi-mi:“MI:0915”(physical association)	0.560
GINS4	BIN3	psi-mi:“MI:0915”(physical association)	0.560
BIN3	ABI2	psi-mi:“MI:0915”(physical association)	0.560
TXLNA	BIN3	psi-mi:“MI:0915”(physical association)	0.560
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
BIN3	ARHGEF37	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
BIN3	E7	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
BIN3	NME2P1	psi-mi:“MI:0914”(association)	0.350
AZU1	STAT3	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): BIN3 (Affinity Capture-RNA), BIN3 (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), SNX5 (Affinity Capture-MS), ARHGEF37 (Affinity Capture-MS), DNMBP (Affinity Capture-MS), SNX1 (Affinity Capture-MS), PICK1 (Affinity Capture-MS), BIN3 (Affinity Capture-MS), BIN3 (Affinity Capture-MS), BIN3 (Affinity Capture-MS), BIN3 (Affinity Capture-MS), BIN3 (Affinity Capture-MS), BIN3 (Affinity Capture-MS), FBXO8 (Affinity Capture-MS)

ESM2 similar proteins: A1XBS5, B0S6J3, D4A208, O35180, O35964, O43295, O75044, P0DJJ0, P0DMP2, P25343, Q08DK5, Q15057, Q1LU86, Q1RMK1, Q2VR06, Q32LM0, Q3SZG6, Q3V2J0, Q5AFE4, Q5FVC7, Q5PPJ9, Q5PPZ5, Q5R8P5, Q5ZIR1, Q5ZJ81, Q5ZK62, Q62419, Q62421, Q68FW8, Q6AYE2, Q6GN09, Q6IVG4, Q6ZQK5, Q6ZTR7, Q7Z6B7, Q812A2, Q8AXU9, Q8BP22, Q8I190, Q8I1C0

Diamond homologs: Q5PPZ5, Q68FW8, Q9JI08, Q9NQY0, Q9UUM7, Q59PE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59770	GRCh38/hg38 8p21.3(chr8:21654619-23001935)x3	Pathogenic

SpliceAI

1979 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22621565:CAAC:C	acceptor_gain	1.0000
8:22621566:AACCT:A	acceptor_loss	1.0000
8:22621567:ACCTG:A	acceptor_loss	1.0000
8:22621568:CCTG:C	acceptor_loss	1.0000
8:22621569:C:CG	acceptor_loss	1.0000
8:22621570:T:A	acceptor_loss	1.0000
8:22623914:CCTGA:C	donor_loss	1.0000
8:22624045:CGTGC:C	acceptor_gain	1.0000
8:22624046:GTGC:G	acceptor_gain	1.0000
8:22624047:TGC:T	acceptor_gain	1.0000
8:22624048:GC:G	acceptor_gain	1.0000
8:22624048:GCC:G	acceptor_loss	1.0000
8:22624049:CC:C	acceptor_gain	1.0000
8:22624049:CCTA:C	acceptor_loss	1.0000
8:22624050:C:CC	acceptor_gain	1.0000
8:22629958:A:AC	donor_gain	1.0000
8:22629959:C:CC	donor_gain	1.0000
8:22629959:CTCA:C	donor_gain	1.0000
8:22629960:TCA:T	donor_loss	1.0000
8:22629961:CACT:C	donor_loss	1.0000
8:22629962:A:AC	donor_gain	1.0000
8:22629962:ACTTT:A	donor_loss	1.0000
8:22629963:C:CA	donor_gain	1.0000
8:22629963:CT:C	donor_gain	1.0000
8:22629963:CTT:C	donor_gain	1.0000
8:22629963:CTTT:C	donor_gain	1.0000
8:22630001:TCAC:T	acceptor_gain	1.0000
8:22630002:CAC:C	acceptor_gain	1.0000
8:22630002:CACC:C	acceptor_gain	1.0000
8:22630004:CCTG:C	acceptor_loss	1.0000

AlphaMissense

1684 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22621438:A:T	I249N	0.999
8:22621444:A:G	L247P	0.999
8:22623928:A:G	L201P	0.999
8:22623939:G:C	S197R	0.999
8:22623939:G:T	S197R	0.999
8:22623941:T:G	S197R	0.999
8:22623994:A:G	L179P	0.999
8:22624319:C:G	R128P	0.999
8:22636534:C:G	A51P	0.999
8:22636563:A:G	L41P	0.999
8:22636584:A:G	L34P	0.999
8:22621453:A:G	L244P	0.998
8:22623920:C:G	A204P	0.998
8:22624049:C:G	A161P	0.998
8:22629973:G:T	P110H	0.998
8:22636928:A:G	L31P	0.998
8:22636949:A:C	F24C	0.998
8:22636949:A:G	F24S	0.998
8:22621438:A:C	I249S	0.997
8:22621438:A:G	I249T	0.997
8:22621444:A:T	L247H	0.997
8:22623982:A:C	M183R	0.997
8:22624002:G:C	N176K	0.997
8:22624002:G:T	N176K	0.997
8:22624014:A:C	F172L	0.997
8:22624014:A:T	F172L	0.997
8:22624016:A:G	F172L	0.997
8:22624229:A:G	L158P	0.997
8:22624231:C:A	K157N	0.997
8:22624231:C:G	K157N	0.997

dbSNP variants (sampled 300 via entrez): RS1000022196 (8:22620118 C>T), RS1000039434 (8:22650938 A>T), RS1000053184 (8:22619963 C>T), RS1000072755 (8:22669348 C>G), RS1000164878 (8:22670410 G>C), RS1000188566 (8:22631912 A>T), RS1000188686 (8:22658966 T>TC), RS1000238247 (8:22626274 A>G), RS1000238535 (8:22623476 G>A,C), RS1000263700 (8:22630237 G>A), RS1000293622 (8:22632306 A>G), RS1000391345 (8:22627937 G>A), RS1000411945 (8:22650735 C>T), RS1000459824 (8:22664214 T>A), RS1000519416 (8:22660103 C>A,T)

Disease associations

OMIM: gene MIM:606396 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003064_10	Exploratory eye movement dysfunction in schizophrenia (cognitive search score)	8.000000e-06
GCST004902_25	Parkinson’s disease	3.000000e-08
GCST006291_11	Spherical equivalent or myopia (age of diagnosis)	2.000000e-08
GCST006979_453	Heel bone mineral density	1.000000e-19
GCST008058_271	Estimated glomerular filtration rate	5.000000e-08
GCST008059_216	Estimated glomerular filtration rate	9.000000e-08
GCST009325_100	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-08
GCST010002_271	Refractive error	2.000000e-17
GCST90014268_20	Cataracts	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007700	exploratory eye movement measurement
EFO:0004847	age at onset
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295959 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
Aflatoxin B1	affects methylation, increases methylation	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases methylation	1
sodium arsenite	affects binding, increases reaction	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Coumestrol	affects cotreatment, increases expression, affects reaction	1
Doxorubicin	increases expression	1
Etoposide	affects response to substance	1
Methapyrilene	affects methylation	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Valproic Acid	increases expression, increases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Mitomycin	affects response to substance	1
Paclitaxel	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118645	Binding	Binding affinity to BIN3 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_E6BE	WA09 BIN3 OE	Embryonic stem cell	Female

Clinical trials (associated diseases)

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