BNIP3

Summary

BNIP3 (BCL2 interacting protein 3, HGNC:1084) is a protein-coding gene on chromosome 10q26.3, encoding BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Q12983). Apoptosis-inducing protein that can overcome BCL2 suppression.

This gene is encodes a mitochondrial protein that contains a BH3 domain and acts as a pro-apoptotic factor. The encoded protein interacts with anti-apoptotic proteins, including the E1B 19 kDa protein and Bcl2. This gene is silenced in tumors by DNA methylation.

Source: NCBI Gene 664 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total — 1 likely-pathogenic
• MANE Select transcript: NM_004052

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1084
Approved symbol	BNIP3
Name	BCL2 interacting protein 3
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	Nip3, HABON
Ensembl gene	ENSG00000176171
Ensembl biotype	protein_coding
OMIM	603293
Entrez	664

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000368636, ENST00000540159, ENST00000631806, ENST00000633835, ENST00000924283, ENST00000924284

RefSeq mRNA: 1 — MANE Select: NM_004052 NM_004052

CCDS: CCDS7663

Canonical transcript exons

ENST00000368636 — 6 exons

Exon	Start	End
ENSE00001270503	131970638	131970787
ENSE00001376359	131970864	131970970
ENSE00001379281	131973034	131973118
ENSE00001384552	131973793	131973943
ENSE00001447634	131967684	131968569
ENSE00002253009	131981761	131981923

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.2478 / max 264.9201, expressed in 1745 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112056	14.4886	1622
112057	13.4889	1717
112058	0.2703	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.63	gold quality
pons	UBERON:0000988	99.22	gold quality
body of pancreas	UBERON:0001150	99.10	gold quality
substantia nigra pars compacta	UBERON:0001965	99.00	gold quality
heart right ventricle	UBERON:0002080	99.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.91	gold quality
postcentral gyrus	UBERON:0002581	98.85	gold quality
parietal lobe	UBERON:0001872	98.83	gold quality
entorhinal cortex	UBERON:0002728	98.80	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.76	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.70	gold quality
cartilage tissue	UBERON:0002418	98.62	gold quality
parotid gland	UBERON:0001831	98.55	gold quality
superior vestibular nucleus	UBERON:0007227	98.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.50	gold quality
superior frontal gyrus	UBERON:0002661	98.34	gold quality
CA1 field of hippocampus	UBERON:0003881	98.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.29	gold quality
biceps brachii	UBERON:0001507	98.27	gold quality
medulla oblongata	UBERON:0001896	98.27	gold quality
nephron tubule	UBERON:0001231	98.24	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.20	gold quality
left ventricle myocardium	UBERON:0006566	98.17	gold quality
ventral tegmental area	UBERON:0002691	98.12	gold quality
diaphragm	UBERON:0001103	98.09	gold quality
choroid plexus epithelium	UBERON:0003911	98.05	gold quality
inferior vagus X ganglion	UBERON:0005363	98.04	gold quality
myocardium	UBERON:0002349	97.93	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.88	gold quality
subthalamic nucleus	UBERON:0001906	97.88	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	517.55
E-MTAB-10042	yes	239.22
E-HCAD-10	yes	30.78
E-MTAB-6701	yes	16.16
E-HCAD-13	yes	12.33
E-CURD-112	yes	10.32
E-MTAB-7316	yes	6.77
E-MTAB-8271	yes	6.59
E-GEOD-125970	yes	4.73
E-MTAB-6819	no	1762.70
E-MTAB-7303	no	1464.45
E-MTAB-8060	no	1109.80
E-MTAB-6524	no	1094.25
E-MTAB-8559	no	912.64
E-MTAB-10596	no	361.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARNT, E2F1, EGR1, EPAS1, FOXO3, HES1, HIF1A, NFKB, NKX6-3, NR3C1, RBPJ, RELA, TP53

miRNA regulators (miRDB)

96 targeting BNIP3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Literature-anchored findings (GeneRIF, showing 40)

• The gene expression of BINP3 was up-regulated during early apoptosis of human hepatoma cells exposed to Paeiniae Radix extract in vitro. (PMID:12215374)
• BNIP3 plays a role in hypoxia-induced cell death in epithelial cells that could be circumvented by growth factor signaling (PMID:12879018)
• Silencing of the hypoxia-inducible cell death protein BNIP3 is associated with pancreatic cancer (PMID:15289340)
• High expression of a hypoxia regulated proapoptotic pathway was associated with a selection of an aggressive phenotype of non-small cell lung cancer. (PMID:15328198)
• Inactivation of BNIP3 likely plays a key role in the progression of some gastrointestinal cancers and that it may be a useful molecular target for therapy. (PMID:15709167)
• loss of BNIP3 expression occurs late in pancreatic cancer, contributes to resistance to chemotherapy, and correlates with a worsened prognosis (PMID:15856026)
• Upregulation of the cell death-related protein BNIP3 is one possible mechanism associated with enterocyte cell death observed in the intestine with NEC. (PMID:16002567)
• In glioblastoma multiforme, BNIP3 expression is increased but it remains sequestered in the nucleus in hypoxic regions, thereby blocking BNIP3’s ability to associate with the mitochondria, providing tumor cells with a possible survival advantage (PMID:16217754)
• pro-apoptotic proteins BNip3 and Nix are expressed in the human placenta (PMID:16219518)
• Loss of Bnip-3 expression is critical for malignant and metastatic evasion of hypoxia-induced cell death (PMID:16357180)
• BNIP3 mediated rapid apoptosis that was triggered by p53 in lung cancer cells. (PMID:16765911)
• data suggest that BNIP3 plays an important role in hypoxic cell death and epigenetic mechanisms selectively silence its expression in colorectal cancer (PMID:16799636)
• we observed no correlation between BNIP3 expression and intratumoral hypoxia. (PMID:16803523)
• Up-regulation of BNIP3 expression in DCIS and invasive carcinoma suggests a significant role in breast tumor progression (PMID:17255267)
• SidF contributes to apoptosis resistance in L. pneumophila-infected cells by specifically interacting with and neutralizing the effects of BNIP3 and Bcl-rambo, two proapoptotic members of Bcl2 protein family. (PMID:17360363)
• In humans, BNIP3 is strongly expressed in most follicular lymphomas, especially those that are Bcl-2 negative. (PMID:17394490)
• Photodynamic therapy resistant HT29 cell variants are differentially sensitized to UVA compared with UVC due, in part at least, through the altered expression levels of BNip3, Hsp27 and mutant p53. (PMID:17576382)
• Results identify BNIP3 as a key regulator of hypoxia-induced autophagy and suggest a novel role for the RB tumor suppressor in preventing nonapoptotic cell death by limiting the extent of BNIP3 induction in cells. (PMID:17576813)
• Ionization state of histidine(173) can mediate structural and dynamic properties of the BNIP3 dimer which, in turn, may be related to pH-dependent BNIP3 proapoptotic activity. (PMID:17600828)
• Elevated levels of the phosphoprotein correlated with initiation of Bnip3-dependent death, whereas the dephosphorylated species correlated with extreme acidosis. (PMID:17638546)
• S100A4 has a role in suppression of BNIP3 expression, chemoresistance, and inhibition of apoptosis in pancreatic cancer (PMID:17638890)
• High levels of BNIP3 expression cannot be used as one of the predicting factors for gemcitabine chemosensitivity of pancreatic neoplasms. (PMID:17729412)
• The study suggests that BNIP3 may actually allow cell survival either by preventing ATP depletion or by eliminating damaged mitochondria. (PMID:17786027)
• Bnip3, a hypoxia-inducible Bcl-2 homology 3 domain-containing protein, directly binds Rheb and inhibits the mTOR pathway. (PMID:17928295)
• Prolonged hypoxia induces autophagic cell death in apoptosis-competent cells, through a mechanism involving BNIP3. (PMID:18059169)
• Increased expression of BNIP3 in the malignant gastric epithelial cells compared to normal mucosal epithelial cells suggests that BNIP3 expression may be involved in gastric carcinoma development. (PMID:18092960)
• BNIP3 is directly regulated by hypoxia but that there may be a hormonal independent mechanism coordinating the expression of BNIP3 in prostate tumors. (PMID:18163427)
• These findings suggest that the suppression of BNIP3 expression by TP prevents, at least in part, hypoxia-induced apoptosis. (PMID:18359286)
• ACAA2 is a functional BNIP3 binding partner and provide a possible linkage between fatty acid metabolism and apoptosis of cells. (PMID:18371312)
• The high expression of HIF-1alpha and BNIP3 were closely related in laryngeal carcinomas. (PMID:18476629)
• Results report that oxygen deprivation can activate the autophagic pathway in human cancer cell lines via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. (PMID:18551130)
• Preserved BNIP3 function in CRC cells lowers apoptosis, and may thus be involved in alternative cell death pathways, such as autophagic cell death. However, BNIP3 silencing in tumour cells does not impact on hypoxia-driven poorer prognosis (PMID:18728663)
• under basal nonapoptotic conditions that NF-kappaB constitutively occupies and transcriptionally silences Bnip3 gene transcription by competing with E2F-1 (PMID:19088195)
• Results suggest that hypoxia-induced autophagy via BNIP3 and BNIP3L is clearly a survival mechanism that promotes tumor progression. (PMID:19273585)
• study showed novel transcriptional repression function for BNIP3 causing reduced apoptosis-inducing factor expression & increased resistance to apoptosis; nuclear BNIP3 may confer survival advantage to glioma cells (PMID:19339613)
• BNIP3 expression is lost in a significant portion of invasive breast cancers (PMID:19505343)
• These findings show that BNIP3 undergoes a dual subcellular localization and initiates different cell death signaling events in the ER and mitochondria. (PMID:19535684)
• The BH3 domain or the C-terminal TM domain determines the cell death function of BNIP3. It plays a role in injured cardiomyocyte death. It is downregulated by promoter hypermethylation or homozygous deletion in some cancers, increased in others. Review. (PMID:19641497)
• SIM2s’ functional interference with HIF1alpha activities on BNIP3 may indicate a novel role for SIM2s in promoting tumourigenesis. (PMID:19668230)
• The small interfering RNA knockdown of BNIP3, IER3, and SEPW1 genes affected critical multiple myeloma endothelial cell functions correlated with the overangiogenic phenotype (PMID:19690192)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bnip3	ENSDARG00000099961
mus_musculus	Bnip3	ENSMUSG00000078566
rattus_norvegicus	Bnip3	ENSRNOG00000017243
drosophila_melanogaster	BNIP3	FBGN0037007
caenorhabditis_elegans		WBGENE00015776

Paralogs (1): BNIP3L (ENSG00000104765)

Protein

Protein identifiers

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 — Q12983 (reviewed: Q12983)

All UniProt accessions (3): Q12983, A0A0J9YW18, B4DHJ7

UniProt curated annotations — full annotation on UniProt →

Function. Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. Plays an important role in the calprotectin (S100A8/A9)-induced cell death pathway.

Subunit / interactions. Homodimer. Binds to BCL2. Interacts with BNIP3L and ACAA2. Interacts (via BH3 domain) with SPATA18 (via coiled-coil domains). Interacts with BOK; promotes BOK oligomerization. Interacts with PPTC7; this interaction promotes BNIP3 degradation. (Microbial infection) Interacts with adenovirus E1B 19 kDa protein. (Microbial infection) Interacts with Epstein-Barr virus BHRF1.

Subcellular location. Mitochondrion. Mitochondrion outer membrane.

Similarity. Belongs to the NIP3 family.

RefSeq proteins (1): NP_004043* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010548	BNIP3	Family

Pfam: PF06553

UniProt features (14 total): modified residue 5, compositionally biased region 3, chain 1, transmembrane region 1, sequence conflict 1, helix 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2J5D	SOLUTION NMR
2KA1	SOLUTION NMR
2KA2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12983-F1	64.64	0.10

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 (5): 92, 95, 54, 66, 86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 390 (showing top): MODULE_97, AP1_01, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_POSITIVE_REGULATION_OF_MITOCHONDRIAL_FISSION, MYOGENIN_Q6, HARRIS_HYPOXIA, GOBP_VACUOLE_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_182, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2

GO Biological Process (45): autophagy of mitochondrion (GO:0000422), mitophagy (GO:0000423), response to hypoxia (GO:0001666), response to bacterium (GO:0009617), positive regulation of autophagy (GO:0010508), negative regulation of mitochondrial fusion (GO:0010637), cardiac muscle cell apoptotic process (GO:0010659), positive regulation of cardiac muscle cell apoptotic process (GO:0010666), negative regulation of mitochondrial membrane potential (GO:0010917), positive regulation of macroautophagy (GO:0016239), cerebral cortex development (GO:0021987), mitochondrial protein catabolic process (GO:0035694), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of programmed cell death (GO:0043068), negative regulation of programmed cell death (GO:0043069), positive regulation of protein-containing complex disassembly (GO:0043243), mitochondrial fragmentation involved in apoptotic process (GO:0043653), negative regulation of membrane potential (GO:0045837), regulation of mitochondrial membrane permeability (GO:0046902), autophagic cell death (GO:0048102), response to axon injury (GO:0048678), oligodendrocyte differentiation (GO:0048709), brown fat cell differentiation (GO:0050873), neuron apoptotic process (GO:0051402), positive regulation of mitochondrial calcium ion concentration (GO:0051561), defense response to virus (GO:0051607), response to hyperoxia (GO:0055093), reticulophagy (GO:0061709), cellular response to hydrogen peroxide (GO:0070301), cellular response to mechanical stimulus (GO:0071260), cellular response to cobalt ion (GO:0071279), cellular response to hypoxia (GO:0071456), reactive oxygen species metabolic process (GO:0072593), positive regulation of mitochondrial fission (GO:0090141), positive regulation of release of cytochrome c from mitochondria (GO:0090200), response to oxygen-glucose deprivation (GO:0090649), mitochondrial outer membrane permeabilization (GO:0097345), granzyme-mediated programmed cell death signaling pathway (GO:0140507), negative regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902109)

GO Molecular Function (6): identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), GTPase binding (GO:0051020), endoplasmic reticulum-autophagosome adaptor activity (GO:0140506), mitochondrion autophagosome adaptor activity (GO:0140580), protein binding (GO:0005515)

GO Cellular Component (13): nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), postsynaptic density (GO:0014069), dendrite (GO:0030425), mitochondrial membrane (GO:0031966), mitochondrial envelope (GO:0005740), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
autophagy	2
macroautophagy	2
apoptotic process	2
regulation of apoptotic process	2
programmed cell death	2
regulation of programmed cell death	2
autophagosome-membrane adaptor activity	2
endomembrane system	2
organelle envelope	2
cytoplasm	2
organelle membrane	2
autophagy of mitochondrion	1
response to stress	1
response to decreased oxygen levels	1
response to other organism	1
positive regulation of catabolic process	1
regulation of autophagy	1
mitochondrial fusion	1
regulation of mitochondrial fusion	1
negative regulation of organelle organization	1
negative regulation of developmental process	1
striated muscle cell apoptotic process	1
cardiac muscle cell apoptotic process	1
positive regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
negative regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
positive regulation of autophagy	1
regulation of macroautophagy	1
pallium development	1
anatomical structure development	1
mitochondrion organization	1
protein catabolic process	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
positive regulation of cellular process	1
negative regulation of cellular process	1

Protein interactions and networks

STRING

2392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BNIP3	BCL2	P10415	998
BNIP3	GABARAP	O95166	994
BNIP3	BCL2L1	Q07817	983
BNIP3	RHEB	Q15382	981
BNIP3	GABARAPL2	P60520	971
BNIP3	F5GZY7	F5GZY7	968
BNIP3	BECN1	Q14457	953
BNIP3	FUNDC1	Q8IVP5	951
BNIP3	MAP1A	P78559	935
BNIP3	VDAC1	P21796	916
BNIP3	MAP1LC3B	Q9GZQ8	916
BNIP3	CD300C	Q08708	905
BNIP3	BNIP2	Q12982	882
BNIP3	HIF1A	Q16665	857
BNIP3	PINK1	Q9BXM7	849

IntAct

252 interactions, top by confidence:

A	B	Type	Score
BNIP3L	BNIP3	psi-mi:“MI:0915”(physical association)	0.970
BNIP3	BNIP3L	psi-mi:“MI:0915”(physical association)	0.970
BNIP3	BNIP3L	psi-mi:“MI:0914”(association)	0.970
BNIP3	TMEM11	psi-mi:“MI:0915”(physical association)	0.920
TMEM11	BNIP3	psi-mi:“MI:0915”(physical association)	0.920
BNIP3	BNIP3	psi-mi:“MI:0915”(physical association)	0.860
BNIP3	PPTC7	psi-mi:“MI:0915”(physical association)	0.800
BNIP3	LDLRAD1	psi-mi:“MI:0915”(physical association)	0.720
FATE1	BNIP3	psi-mi:“MI:0915”(physical association)	0.720
BNIP3	FATE1	psi-mi:“MI:0915”(physical association)	0.720
LDLRAD1	BNIP3	psi-mi:“MI:0915”(physical association)	0.720
CLEC7A	BNIP3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (168): BNIP3 (Two-hybrid), BNIP3L (Two-hybrid), KTN1 (Two-hybrid), TMEM11 (Two-hybrid), CLEC7A (Two-hybrid), FATE1 (Two-hybrid), LDLRAD1 (Two-hybrid), BNIP3 (Affinity Capture-Western), BNIP3 (Two-hybrid), OPA1 (Reconstituted Complex), BNIP3 (Affinity Capture-MS), BNIP3 (Affinity Capture-MS), TMEM11 (Two-hybrid), BNIP3L (Two-hybrid), BNIP3 (Two-hybrid)

ESM2 similar proteins: A0AUQ6, A2BE76, O14645, O18973, O35427, O35473, O55003, O88447, O88597, P50503, Q05B58, Q12983, Q13901, Q14457, Q14AM7, Q14CZ0, Q28HY5, Q32KN2, Q32PE4, Q4A1L3, Q4A1L4, Q4A1L5, Q4R3K5, Q4R8N2, Q4RLT3, Q52LA3, Q5JSJ4, Q5NVP8, Q5R878, Q5RBU4, Q5TKA1, Q5ZHS3, Q5ZJQ3, Q68FJ8, Q6DKA1, Q6GMH0, Q6GP52, Q6PAX8, Q6X4M3, Q7TSU0

Diamond homologs: A8XPY4, O55003, Q09969, Q12983, O60238, Q32KN2, Q3T013, Q9Z2F7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
BNIP3	down-regulates	RHEB	binding
“HIF-1 complex”	“up-regulates quantity by expression”	BNIP3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442270	GRCh37/hg19 10q26.3(chr10:130693843-134772865)x1	Likely pathogenic

SpliceAI

978 predictions. Top by Δscore:

Variant	Effect	Δscore
10:131973120:T:C	acceptor_gain	1.0000
10:131973120:T:TC	acceptor_gain	1.0000
10:131973124:C:CT	acceptor_gain	1.0000
10:131973125:G:T	acceptor_gain	1.0000
10:131973126:A:AC	acceptor_gain	1.0000
10:131973128:G:GC	acceptor_gain	1.0000
10:131973132:A:AC	acceptor_gain	1.0000
10:131973132:A:C	acceptor_gain	1.0000
10:131973137:A:AC	acceptor_gain	1.0000
10:131973137:A:C	acceptor_gain	1.0000
10:131973788:CCTA:C	donor_loss	1.0000
10:131973790:TA:T	donor_loss	1.0000
10:131973791:AC:A	donor_loss	1.0000
10:131973792:C:A	donor_loss	1.0000
10:131973944:C:CC	acceptor_gain	1.0000
10:131981759:AC:A	donor_gain	1.0000
10:131981760:CC:C	donor_gain	1.0000
10:131981772:T:A	donor_gain	1.0000
10:131981775:T:TA	donor_gain	1.0000
10:131969468:A:T	acceptor_gain	0.9900
10:131970784:CTCC:C	acceptor_gain	0.9900
10:131970862:A:AC	donor_gain	0.9900
10:131970863:C:CC	donor_gain	0.9900
10:131970890:TG:T	donor_gain	0.9900
10:131970971:C:CC	acceptor_gain	0.9900
10:131973028:GCTTA:G	donor_loss	0.9900
10:131973029:CTTA:C	donor_loss	0.9900
10:131973030:TTAC:T	donor_loss	0.9900
10:131973031:TAC:T	donor_loss	0.9900
10:131973032:ACCT:A	donor_loss	0.9900

AlphaMissense

1691 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:131970638:C:T	G245E	0.998
10:131970639:C:G	G245R	0.998
10:131970639:C:T	G245R	0.998
10:131970644:C:T	G243E	0.997
10:131973938:A:G	W83R	0.997
10:131973938:A:T	W83R	0.997
10:131970659:T:C	H238R	0.996
10:131970893:C:A	W185C	0.996
10:131970893:C:G	W185C	0.996
10:131970895:A:G	W185R	0.996
10:131970895:A:T	W185R	0.996
10:131973837:C:A	Q116H	0.996
10:131973837:C:G	Q116H	0.996
10:131973850:A:G	L112P	0.996
10:131973850:A:T	L112Q	0.996
10:131973936:C:A	W83C	0.996
10:131973936:C:G	W83C	0.996
10:131970660:G:C	H238D	0.994
10:131973842:C:G	A115P	0.994
10:131968558:C:T	G249E	0.993
10:131970650:G:T	A241D	0.993
10:131970671:A:G	L234P	0.993
10:131970677:G:T	P232Q	0.993
10:131970645:C:G	G243R	0.992
10:131970645:C:T	G243R	0.992
10:131973847:A:G	L113P	0.992
10:131968561:A:T	I248N	0.991
10:131970658:A:C	H238Q	0.991
10:131970658:A:T	H238Q	0.991
10:131970677:G:C	P232R	0.990

dbSNP variants (sampled 300 via entrez): RS1000193384 (10:131971437 G>A), RS1000205488 (10:131977284 A>G), RS1000485806 (10:131981105 T>C), RS1000494090 (10:131967253 T>C), RS1000581616 (10:131981431 C>A), RS1000814461 (10:131975620 G>A), RS1000881064 (10:131981376 A>G), RS1001169213 (10:131983620 A>T), RS1001216292 (10:131980119 A>C), RS1001694018 (10:131977710 T>G), RS1001703730 (10:131983894 G>A), RS1001725397 (10:131977458 G>A), RS1002256258 (10:131982724 C>T), RS1002320922 (10:131969678 C>T), RS1002614692 (10:131982573 A>C)

Disease associations

OMIM: gene MIM:603293 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008595_147	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	4.000000e-08
GCST009391_523	Metabolite levels	7.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0010117	pyruvate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	affects binding, increases reaction, decreases reaction, increases expression, affects reaction (+2 more)	10
Valproic Acid	affects reaction, increases expression, increases reaction, affects cotreatment, affects expression (+3 more)	10
sodium arsenite	increases expression, decreases reaction, decreases expression, affects binding, increases stability (+2 more)	9
cobaltous chloride	increases expression, decreases reaction	5
Decitabine	affects expression, decreases methylation, increases expression	5
Paraquat	increases expression, increases reaction, decreases expression, affects response to substance, affects cotreatment (+1 more)	5
Cisplatin	affects cotreatment, increases expression, decreases expression, decreases response to substance, decreases reaction (+1 more)	4
Hydrogen Peroxide	decreases reaction, affects expression, affects cotreatment, affects reaction, decreases expression	4
Cyclosporine	decreases expression, decreases reaction, increases expression	4
Cadmium Chloride	decreases reaction, increases expression, decreases expression, affects reaction	4
Particulate Matter	increases abundance, affects cotreatment, affects expression, increases reaction, decreases expression	4
bisphenol A	affects expression, decreases expression, decreases methylation	3
Arsenic Trioxide	increases response to substance, affects cotreatment, decreases expression, decreases reaction, increases expression	3
Acetaminophen	decreases expression, increases expression, affects cotreatment	3
Cobalt	increases expression, affects binding, affects cotreatment	3
Melatonin	affects cotreatment, increases reaction, affects reaction, decreases reaction, increases expression	3
tungsten carbide	affects binding, increases expression, affects cotreatment	2
methylmercuric chloride	decreases expression	2
nickel chloride	increases expression, increases reaction	2
3-methyladenine	decreases reaction, increases expression, decreases expression	2
bafilomycin A1	increases expression, increases cleavage, increases reaction, affects reaction, decreases reaction	2
Zoledronic Acid	decreases expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Ethanol	decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Capsaicin	decreases expression, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Fluorouracil	affects response to substance, affects reaction, decreases expression	2
Formaldehyde	decreases reaction, increases expression, decreases expression	2
Methotrexate	affects response to substance, affects cotreatment, decreases expression	2

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1HA	HeLa S3 BNIP3/BNIP3L DKO clone 6	Cancer cell line	Female
CVCL_E1HB	HeLa S3 BNIP3/BNIP3L DKO clone 10	Cancer cell line	Female
CVCL_E6FB	HeLa S3 BNIP3L KO clone #17	Cancer cell line	Female
CVCL_SF43	HAP1 BNIP3 (-) 1	Cancer cell line	Male
CVCL_XM05	HAP1 BNIP3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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