BRI3BP

Summary

BRI3BP (BRI3 binding protein, HGNC:14251) is a protein-coding gene on chromosome 12q24.31, encoding BRI3-binding protein (Q8WY22). Involved in tumorigenesis and may function by stabilizing p53/TP53.

Located in mitochondrion.

Source: NCBI Gene 140707 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• Druggable target: yes
• MANE Select transcript: NM_080626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14251
Approved symbol	BRI3BP
Name	BRI3 binding protein
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	BNAS1, KG19, HCCR-2, HCCRBP-3
Ensembl gene	ENSG00000184992
Ensembl biotype	protein_coding
OMIM	615627
Entrez	140707

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000341446, ENST00000671775, ENST00000672415

RefSeq mRNA: 1 — MANE Select: NM_080626 NM_080626

CCDS: CCDS9262

Canonical transcript exons

ENST00000341446 — 3 exons

Exon	Start	End
ENSE00001298943	124993645	124994003
ENSE00001326539	125012534	125012636
ENSE00001385032	125024991	125031231

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.8941 / max 303.4454, expressed in 1764 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128657	7.2709	1663
128659	4.3902	1174
128658	2.6178	1087
128656	0.4132	222
128662	0.2018	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.40	gold quality
upper arm skin	UBERON:0004263	97.25	gold quality
jejunal mucosa	UBERON:0000399	96.58	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.40	gold quality
colonic mucosa	UBERON:0000317	95.99	gold quality
mammalian vulva	UBERON:0000997	95.65	gold quality
upper leg skin	UBERON:0004262	95.28	gold quality
endothelial cell	CL:0000115	95.25	gold quality
oocyte	CL:0000023	94.23	gold quality
cerebellar vermis	UBERON:0004720	93.96	gold quality
pons	UBERON:0000988	93.55	gold quality
pancreatic ductal cell	CL:0002079	93.35	gold quality
esophagus squamous epithelium	UBERON:0006920	93.25	gold quality
oviduct epithelium	UBERON:0004804	93.21	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.10	gold quality
epithelial cell of pancreas	CL:0000083	93.07	gold quality
parietal lobe	UBERON:0001872	92.99	gold quality
nipple	UBERON:0002030	92.87	gold quality
postcentral gyrus	UBERON:0002581	92.85	gold quality
secondary oocyte	CL:0000655	92.84	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.65	gold quality
inferior vagus X ganglion	UBERON:0005363	92.29	gold quality
pylorus	UBERON:0001166	92.15	gold quality
gingival epithelium	UBERON:0001949	91.79	gold quality
superior vestibular nucleus	UBERON:0007227	91.64	gold quality
duodenum	UBERON:0002114	91.57	gold quality
superior frontal gyrus	UBERON:0002661	91.40	gold quality
ventral tegmental area	UBERON:0002691	91.37	gold quality
tibia	UBERON:0000979	91.32	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting BRI3BP, 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-6740-5P	100.00	65.64	932
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-4646-5P	97.70	66.84	1692

Literature-anchored findings (GeneRIF, showing 3)

• highly expressed in brain, kidney, and liver; mapped to human chromosome 12q24.2-qter (PMID:11860200)
• Taken together, BRI3BP, widely expressed in animal cell types, seems to possess a pro-apoptotic property and can potentiate drug-induced apoptosis. (PMID:17765869)
• HCCRBP-3 induces tumorigenesis through direct interaction with HCCR-1 in human cancers. (PMID:22851403)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bri3bp	ENSDARG00000010108
mus_musculus	Bri3bp	ENSMUSG00000037905
rattus_norvegicus	Bri3bp	ENSRNOG00000063640

Protein

Protein identifiers

BRI3-binding protein — Q8WY22 (reviewed: Q8WY22)

Alternative names: Cervical cancer 1 proto-oncogene-binding protein KG19, HCCRBP-1

All UniProt accessions (2): Q8WY22, A0A5F9ZHY7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in tumorigenesis and may function by stabilizing p53/TP53.

Subunit / interactions. Interacts with LETMD1. Interacts with BRI3 (isoforms 1 and 2); the interaction with isoform 2 is weaker than with isoform 1. Interacts with BRI3; the interaction is weak. Interacts with TMEM238L.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Most abundantly expressed in brain, liver and kidney. Overexpressed in leukemia and lymphoma cell lines, as well as in various carcinomas.

RefSeq proteins (1): NP_542193* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033367	BRI3BP	Family

Pfam: PF14965

UniProt features (9 total): transmembrane region 4, modified residue 2, chain 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WY22-F1	63.83	0.04

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 (2): 229, 248

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): BILD_E2F3_ONCOGENIC_SIGNATURE, GOCC_MITOCHONDRIAL_ENVELOPE, GARY_CD5_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, CUI_TCF21_TARGETS_2_UP, SENESE_HDAC3_TARGETS_DN, NUYTTEN_EZH2_TARGETS_DN, chr12q24, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C, GOCC_ORGANELLE_ENVELOPE, CHICAS_RB1_TARGETS_SENESCENT, DUTERTRE_ESTRADIOL_RESPONSE_6HR_UP, DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP, BILANGES_RAPAMYCIN_SENSITIVE_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

117 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
TMED9	TMED10	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
BRI3	BRI3BP	psi-mi:“MI:0915”(physical association)	0.570
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
LRRC4C	DVL2	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GDE1	GAPDHS	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
SMPD3	ENDOD1	psi-mi:“MI:0914”(association)	0.530
CD63	LGALS8	psi-mi:“MI:0914”(association)	0.530
TOR1A	TOR1B	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
SIGMAR1	NPC1	psi-mi:“MI:0914”(association)	0.530
PRRT2	NDUFB3	psi-mi:“MI:0914”(association)	0.530
TMEM43	ENDOD1	psi-mi:“MI:0914”(association)	0.530
LETMD1	BRI3BP	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (157): BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Affinity Capture-MS), BRI3BP (Proximity Label-MS), BRI3BP (Proximity Label-MS), BRI3BP (Proximity Label-MS), BRI3BP (Affinity Capture-MS)

ESM2 similar proteins: A0JN53, A0PJX8, A1L1L2, A1L3T7, A4FV45, B0BMG8, E2JF22, G3HQ82, O15360, O43299, O70491, P60330, Q0KL00, Q0V8E7, Q17Q97, Q24JP3, Q3U829, Q49LS3, Q4QR83, Q562E7, Q5ND34, Q5R7B4, Q5T1A1, Q5XG04, Q6NUQ4, Q6PH58, Q6UX68, Q7L4E1, Q7Z412, Q8BGI5, Q8BM55, Q8BSD4, Q8BXV2, Q8C3R1, Q8C7B8, Q8IXR5, Q8K0R6, Q8N6S5, Q8R115, Q8VCA6

Diamond homologs: Q8BXV2, Q8WY22

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Calnexin/calreticulin cycle	5	36.0×	9e-05
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	5	21.4×	8e-04
Defective CFTR causes cystic fibrosis	6	13.3×	9e-04
Disorders of transmembrane transporters	7	9.8×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	8	10.7×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1084 predictions. Top by Δscore:

Variant	Effect	Δscore
12:124994000:GAAG:G	donor_gain	1.0000
12:124994001:AAGG:A	donor_loss	1.0000
12:124994002:AGG:A	donor_loss	1.0000
12:124994003:GGTG:G	donor_loss	1.0000
12:124994004:G:A	donor_loss	1.0000
12:124994005:T:A	donor_loss	1.0000
12:125012532:A:AG	acceptor_gain	1.0000
12:125012533:G:GG	acceptor_gain	1.0000
12:125012636:GGTA:G	donor_loss	1.0000
12:125012637:G:GA	donor_loss	1.0000
12:125012638:T:A	donor_loss	1.0000
12:125012529:TGCA:T	acceptor_loss	0.9900
12:125012529:TGCAG:T	acceptor_gain	0.9900
12:125012530:GCAG:G	acceptor_loss	0.9900
12:125012530:GCAGT:G	acceptor_gain	0.9900
12:125012531:CA:C	acceptor_loss	0.9900
12:125012532:A:G	acceptor_loss	0.9900
12:125012533:G:GT	acceptor_loss	0.9900
12:125012533:GT:G	acceptor_gain	0.9900
12:125012533:GTT:G	acceptor_gain	0.9900
12:125012533:GTTC:G	acceptor_gain	0.9900
12:125012533:GTTCT:G	acceptor_gain	0.9900
12:125012637:G:GG	donor_gain	0.9900
12:125024989:A:AG	acceptor_gain	0.9900
12:125024990:G:GA	acceptor_gain	0.9900
12:124994752:G:GT	donor_gain	0.9800
12:125012528:CTGCA:C	acceptor_gain	0.9800
12:125012597:A:T	donor_gain	0.9800
12:125025117:GC:G	acceptor_gain	0.9800
12:125012531:CAG:C	acceptor_gain	0.9700

AlphaMissense

1605 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:125025182:T:C	C170R	0.997
12:125025239:T:C	C189R	0.997
12:125025252:C:A	A193D	0.996
12:125025387:T:C	L238P	0.995
12:125025237:T:A	L188Q	0.993
12:125025237:T:G	L188R	0.993
12:125012603:T:A	W95R	0.992
12:125012603:T:C	W95R	0.992
12:125025083:T:A	W137R	0.992
12:125025083:T:C	W137R	0.992
12:125025171:T:C	F166S	0.992
12:125025195:T:C	L174P	0.992
12:125025375:T:C	L234P	0.992
12:125025257:T:G	Y195D	0.991
12:125025062:G:C	G130R	0.990
12:125025149:T:A	W159R	0.990
12:125025149:T:C	W159R	0.990
12:125025237:T:C	L188P	0.990
12:125025246:T:A	V191E	0.990
12:125025188:T:G	Y172D	0.989
12:124993960:T:A	V57D	0.988
12:125025255:T:A	V194D	0.988
12:124993975:G:T	G62V	0.987
12:125025168:T:G	L165R	0.987
12:125025257:T:C	Y195H	0.987
12:125025354:T:C	L227P	0.987
12:125012567:G:A	G83R	0.986
12:125012567:G:C	G83R	0.986
12:125025170:T:C	F166L	0.986
12:125025172:T:A	F166L	0.986

dbSNP variants (sampled 300 via entrez): RS1000001580 (12:124997984 C>T), RS1000024313 (12:125009123 G>A), RS1000057568 (12:125032937 G>A), RS1000107563 (12:125017958 C>A,T), RS1000108634 (12:125003311 G>A), RS1000185900 (12:125019050 A>G), RS1000192125 (12:125012636 G>A), RS1000276396 (12:125030571 T>C), RS1000363914 (12:125024998 C>A,G), RS1000441374 (12:125042150 T>G), RS1000458016 (12:124998092 C>T), RS1000476683 (12:125024716 T>C), RS1000536248 (12:125033171 A>G), RS1000548435 (12:125002126 T>G), RS1000613818 (12:125008036 C>T)

Disease associations

OMIM: gene MIM:615627 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067074 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.00	Kd	9981	nM	CHEMBL5653589
5.00	ED50	9981	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147957: Binding affinity to human BRI3BP incubated for 45 mins by Kinobead based pull down assay	kd	9.9806	uM

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
sodium arsenite	decreases expression, increases expression	3
bisphenol A	affects expression, decreases methylation	2
trichostatin A	increases expression	2
perfluorooctanoic acid	decreases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Estradiol	affects binding, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Panobinostat	increases expression	1
Acetaminophen	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
CHEMBL5650999	Binding	Binding affinity to human BRI3BP incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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