BNIP3L

Summary

BNIP3L (BCL2 interacting protein 3 like, HGNC:1085) is a protein-coding gene on chromosome 8p21.2, encoding BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (O60238). Induces apoptosis.

This gene encodes a protein that belongs to the pro-apoptotic subfamily within the Bcl-2 family of proteins. The encoded protein binds to Bcl-2 and possesses the BH3 domain. The protein directly targets mitochondria and causes apoptotic changes, including loss of membrane potential and the release of cytochrome c.

Source: NCBI Gene 665 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_004331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1085
Approved symbol	BNIP3L
Name	BCL2 interacting protein 3 like
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	Nix, BNIP3a
Ensembl gene	ENSG00000104765
Ensembl biotype	protein_coding
OMIM	605368
Entrez	665

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000380629, ENST00000518611, ENST00000520077, ENST00000520409, ENST00000521254, ENST00000523515, ENST00000523949, ENST00000877444, ENST00000877445

RefSeq mRNA: 2 — MANE Select: NM_004331 NM_001330491, NM_004331

CCDS: CCDS6050, CCDS83267

Canonical transcript exons

ENST00000380629 — 6 exons

Exon	Start	End
ENSE00001120127	26395230	26395302
ENSE00001879265	26410364	26413127
ENSE00002121374	26383054	26383230
ENSE00003543952	26391243	26391426
ENSE00003621010	26408227	26408376
ENSE00003689825	26408000	26408103

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 212.3966 / max 28011.2609, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88040	132.3298	1828
88044	79.3129	276
88042	0.7249	351
88041	0.0289	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.42	gold quality
mammary duct	UBERON:0001765	98.79	gold quality
ventricular zone	UBERON:0003053	98.73	gold quality
nipple	UBERON:0002030	98.67	gold quality
pericardium	UBERON:0002407	98.65	gold quality
lateral globus pallidus	UBERON:0002476	98.64	gold quality
corpus epididymis	UBERON:0004359	98.63	gold quality
bone marrow	UBERON:0002371	98.62	gold quality
inferior vagus X ganglion	UBERON:0005363	98.57	gold quality
caput epididymis	UBERON:0004358	98.55	gold quality
monocyte	CL:0000576	98.52	gold quality
corpus callosum	UBERON:0002336	98.52	gold quality
cartilage tissue	UBERON:0002418	98.49	gold quality
parietal pleura	UBERON:0002400	98.48	gold quality
pons	UBERON:0000988	98.47	gold quality
seminal vesicle	UBERON:0000998	98.46	gold quality
postcentral gyrus	UBERON:0002581	98.44	gold quality
cortical plate	UBERON:0005343	98.41	gold quality
mononuclear cell	CL:0000842	98.36	gold quality
blood	UBERON:0000178	98.33	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.33	gold quality
parietal lobe	UBERON:0001872	98.32	gold quality
vena cava	UBERON:0004087	98.31	gold quality
amniotic fluid	UBERON:0000173	98.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.27	gold quality
cauda epididymis	UBERON:0004360	98.27	gold quality
lower lobe of lung	UBERON:0008949	98.26	gold quality
subthalamic nucleus	UBERON:0001906	98.25	gold quality
globus pallidus	UBERON:0001875	98.23	gold quality
pleura	UBERON:0000977	98.22	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	552.12
E-MTAB-8142	yes	41.42
E-GEOD-134144	yes	30.93
E-MTAB-9221	yes	28.67
E-HCAD-13	yes	13.65
E-HCAD-9	yes	10.35
E-MTAB-9467	yes	4.81
E-CURD-98	no	1170.11
E-MTAB-6075	no	811.57
E-GEOD-125970	no	3.47
E-HCAD-10	no	2.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, HIF1A, TP53

miRNA regulators (miRDB)

154 targeting BNIP3L, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192

Literature-anchored findings (GeneRIF, showing 40)

• NIX binds to TSAP6 in tumor cells and has a role in apoptosis (PMID:12606722)
• The proapoptotic factor Nix is a highly regulated effector of growth during terminal erythroid maturation. (PMID:12663450)
• Bnip3L, capable of attenuating tumorigenicity, mediates p53-dependent apoptosis under hypoxia. (PMID:15607964)
• pro-apoptotic proteins BNip3 and Nix are expressed in the human placenta (PMID:16219518)
• NIX is required for the selective elimination of mitochondria, however, because mitochondrial clearance, in the absence of NIX, is arrested at the stage of mitochondrial incorporation into autophagosomes and autophagosome maturation. (PMID:18048346)
• 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)
• Homozygous deletions in a number of biologically important genes were found in prostate cancer cell lines, including PPP2R2A and BNIP3L identified in this study. (PMID:18670647)
• Results suggest that hypoxia-induced autophagy via BNIP3 and BNIP3L is clearly a survival mechanism that promotes tumor progression. (PMID:19273585)
• Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation (PMID:20010802)
• mitochondrial ROS and NIX are essential factors for Mieap-induced accumulation of lysosome-like organelles within mitochondria (PMID:21264228)
• The physical interaction of Mieap, BNIP3 and NIX at the mitochondrial outer membrane may play a critical role in the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. (PMID:22292033)
• Nix protein positively regulates NF-kappaB activation in gliomas (PMID:22984526)
• regulates mitophagy during hypoxia, whereas NIX is required for mitophagy during development of the erythroid lineage. (PMID:25753537)
• Data suggest that targeting BNIP3L protein in wild-type p53 tumor suppressor colon cancer cells is an anticancer strategy activating iron depletion signaling and the mitophagy-related cell death pathway. (PMID:26517689)
• The authors find that KDM3A promotes anoikis through transcriptional activation of BNIP3 and BNIP3L, which encode pro-apoptotic proteins. (PMID:27472901)
• p75(NTR) and NIX may play critical roles in intracerebral hemorrhage-induced neuronal apoptosis in vitro and in vivo. (PMID:27726026)
• The results demonstrate that Nix can serve as an alternative mediator of mitophagy to maintain mitochondrial turnover, identifying Nix as a promising target for neuroprotective treatment in PINK1/Parkin-related Parkinson’s disease. (PMID:28281653)
• Here the authors present evidence for phosphorylation-driven regulation of the Nix:LC3B interaction. Isothermal titration calorimetry and NMR indicate a ~100 fold enhanced affinity of the serine 34/35-phosphorylated Nix LC3-interacting region (LIR) to LC3B and formation of a very rigid complex compared to the non-phosphorylated sequence. (PMID:28442745)
• NIX-mediated mitophagy is suppressed in proteinuric conditions and is responsible for proteinuria- induced cell apoptosis, which is consistent with previous evidence that excess albumin uptake inhibits autophagy in renal tubules and contributes to progressive tubular injury. (PMID:30207166)
• chronic obstructive pulmonary disease (COPD)patients had lower muscle mitochondrial content, higher BNIP3L and lower FUNDC1 protein, and higher Parkin protein and gene-expression. BNIP3L and Parkin protein levels inversely correlated with mtDNA/gDNA ratio and FEV1% predicted. (PMID:30302028)
• These data suggest that Nix-dependent mitophagy promotes airway epithelial cell and mitochondria injury induced by cigarette smoke, and may be involved in the pathogenesis of chronic obstructive pulmonary disease and other cigarette smoke-associated diseases (PMID:30618073)
• Mieap-induced accumulation of lysosomes within mitochondria (MALM) regulates gastric cancer cell invasion under hypoxia by suppressing reactive oxygen species accumulation. (PMID:30808977)
• NIX-mediated mitophagy is a new oncogenic KRAS effector pathway that suppresses functional mitochondrial content to stimulate cell proliferation and augment redox homeostasis. This pathway promotes the progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) and represents a new dependency in pancreatic cancer. (PMID:31263025)
• NIX was overexpressed in the pseudopalisading cells that envelop the hypoxic-necrotic regions, and mitochondrial NIX expression was robust in patient-derived glioblastoma tumor tissues and glioblastoma stem cells. NIX was required for hypoxia and oxidative stress-induced mitophagy through NFE2L2/NRF2 transactivation.NIX expression was associated with poor outcome for patients with glioblastoma. (PMID:31488423)
• present the results of analysis of BNIP3 and BNIP3L/Nix proteins in cells harboring a combination of the 11778G>A and the 3460G>A Leber’s Hereditary Optic Neuropathy mutations (PMID:31584786)
• Dimerization of mitophagy receptor BNIP3L/NIX is essential for recruitment of autophagic machinery. (PMID:32286918)
• Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene. (PMID:32393399)
• BNIP3L is a candidate prognostic marker. (PMID:32620611)
• Hypoxia regulates the degradation of non-nuclear organelles during lens differentiation through activation of HIF1a. (PMID:32628953)
• BNIP3L/Nix-induced mitochondrial fission, mitophagy, and impaired myocyte glucose uptake are abrogated by PRKA/PKA phosphorylation. (PMID:33044904)
• [Knockdown of ALAS2 Affects Erythroid Differentiation by Down-regulating Mitophagy Receptor BNIP3L]. (PMID:33067979)
• NIX-mediated mitophagy regulate metabolic reprogramming in phagocytic cells during mycobacterial infection. (PMID:33421909)
• NIX initiates mitochondrial fragmentation via DRP1 to drive epidermal differentiation. (PMID:33535046)
• Expression and Clinical Significance of BCL2 Interacting Protein 3 Like in Multiple Myeloma. (PMID:34189969)
• A brief overview of BNIP3L/NIX receptor-mediated mitophagy. (PMID:34597467)
• BNIP3 and Nix: Atypical regulators of cell fate. (PMID:35863652)
• Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis. (PMID:36766737)
• The outer mitochondrial membrane protein TMEM11 demarcates spatially restricted BNIP3/BNIP3L-mediated mitophagy. (PMID:36795401)
• FBXL4 ubiquitin ligase deficiency promotes mitophagy by elevating NIX levels. (PMID:37102372)
• Uncovering interactions of mitochondrial proteins BNIP3 and BNIP3L with necroptosis-associated kinase RIPK3: Insights into kinase activation. (PMID:37419035)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	bnip3la	ENSDARG00000025468
danio_rerio	bnip3lb	ENSDARG00000028067
mus_musculus	Bnip3l	ENSMUSG00000022051
rattus_norvegicus	Bnip3l	ENSRNOG00000009820
drosophila_melanogaster	BNIP3	FBGN0037007
caenorhabditis_elegans		WBGENE00015776

Paralogs (1): BNIP3 (ENSG00000176171)

Protein

Protein identifiers

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like — O60238 (reviewed: O60238)

Alternative names: Adenovirus E1B19K-binding protein B5, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3A, NIP3-like protein X

All UniProt accessions (4): E5RFE9, O60238, H0YBC7, Q6IBV1

UniProt curated annotations — full annotation on UniProt →

Function. Induces apoptosis. Interacts with viral and cellular anti-apoptosis proteins. Can overcome the suppressors BCL-2 and BCL-XL, although high levels of BCL-XL expression will inhibit apoptosis. Inhibits apoptosis induced by BNIP3. 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. May function as a tumor suppressor.

Subunit / interactions. Self-associates. Interacts with BNIP3 and STEAP3. Interacts (via BH3 domain) with SPATA18 (via coiled-coil domains). Interacts with PPTC7; this interaction promotes BNIP3L degradation. (Microbial infection) Interacts with human adenovirus-2 E1B 19 kDa protein. (Microbial infection) Interacts with Kaposi’s sarcoma-associated herpesvirus protein VIRF-1.

Subcellular location. Nucleus envelope. Endoplasmic reticulum. Mitochondrion outer membrane. Membrane.

Post-translational modifications. Undergoes progressive proteolysis to an 11 kDa C-terminal fragment, which is blocked by the proteasome inhibitor lactacystin.

Similarity. Belongs to the NIP3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60238-1	1	yes
O60238-2	2

RefSeq proteins (2): NP_001317420, NP_004322* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010548	BNIP3	Family

Pfam: PF06553

UniProt features (15 total): modified residue 5, compositionally biased region 3, sequence conflict 2, chain 1, transmembrane region 1, splice variant 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60238-F1	60.73	0.08

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): 120, 166, 62, 117, 118

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633008	TP53 Regulates Transcription of Cell Death Genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 354 (showing top): AGGAAGC_MIR5163P, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_REGULATION_OF_AUTOPHAGY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, HARRIS_HYPOXIA, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, KYNG_DNA_DAMAGE_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, IIZUKA_LIVER_CANCER_PROGRESSION_L1_G1_UP, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN

GO Biological Process (14): negative regulation of mitochondrial membrane potential (GO:0010917), positive regulation of macroautophagy (GO:0016239), mitochondrial protein catabolic process (GO:0035694), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), regulation of programmed cell death (GO:0043067), negative regulation of programmed cell death (GO:0043069), defense response to virus (GO:0051607), cellular response to hypoxia (GO:0071456), mitochondrial outer membrane permeabilization (GO:0097345), regulation of mitophagy (GO:1901524), obsolete regulation of protein targeting to mitochondrion (GO:1903214), apoptotic process (GO:0006915), positive regulation of mitochondrial membrane permeability (GO:0035794)

GO Molecular Function (4): lamin binding (GO:0005521), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nuclear envelope (GO:0005635), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), nuclear speck (GO:0016607), mitochondrial envelope (GO:0005740), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
programmed cell death	3
intracellular membrane-bounded organelle	3
regulation of macroautophagy	2
apoptotic process	2
regulation of apoptotic process	2
apoptotic signaling pathway	2
protein binding	2
endomembrane system	2
organelle envelope	2
cytoplasm	2
negative regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
positive regulation of autophagy	1
macroautophagy	1
mitochondrion organization	1
protein catabolic process	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
regulation of cellular process	1
regulation of programmed cell death	1
negative regulation of cellular process	1
defense response	1
response to virus	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
positive regulation of mitochondrial membrane permeability involved in apoptotic process	1
mitophagy	1
regulation of autophagy of mitochondrion	1
execution phase of apoptosis	1
regulation of mitochondrial membrane permeability	1
positive regulation of membrane permeability	1
identical protein binding	1
protein dimerization activity	1
binding	1
nucleus	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BNIP3L	GABARAP	O95166	995
BNIP3L	F5GZY7	F5GZY7	994
BNIP3L	BCL2	P10415	992
BNIP3L	GABARAPL2	P60520	990
BNIP3L	RHEB	Q15382	967
BNIP3L	FUNDC1	Q8IVP5	967
BNIP3L	MAP1A	P78559	940
BNIP3L	BCL2L1	Q07817	930
BNIP3L	MAP1LC3B	Q9GZQ8	900
BNIP3L	BECN1	Q14457	871
BNIP3L	PINK1	Q9BXM7	856
BNIP3L	CD300C	Q08708	849
BNIP3L	NBR1	Q14596	829
BNIP3L	PKMYT1	Q99640	823
BNIP3L	BCL2L13	Q9BXK5	817

IntAct

151 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
BNIP3L	BNIP3L	psi-mi:“MI:0915”(physical association)	0.860

BioGRID (126): BNIP3L (Two-hybrid), BNIP3L (Two-hybrid), TMEM11 (Two-hybrid), SMCO4 (Two-hybrid), CLEC7A (Two-hybrid), FATE1 (Two-hybrid), LDLRAD1 (Two-hybrid), BNIP3 (Affinity Capture-MS), DOK5 (Two-hybrid), BNIP3L (Affinity Capture-MS), EWSR1 (Two-hybrid), BNIP3L (Two-hybrid), BNIP3L (Two-hybrid), TMEM11 (Two-hybrid), BNIP3L (Reconstituted Complex)

ESM2 similar proteins: A0JP43, A1YEW9, A2D4U8, A2D5N1, A2D671, A2T6K9, A8T6P4, B8AE37, F6QRE9, G3V9A7, O60238, P48785, P79149, Q0IIJ3, Q0P6D6, Q15170, Q15361, Q15390, Q2KIJ9, Q3T013, Q3ULM0, Q3ZBJ9, Q4V7L5, Q5H9J7, Q5NVG8, Q5PPP3, Q5PR69, Q5RFN3, Q5W0A0, Q66HD8, Q67XL4, Q6K678, Q86X53, Q8BP27, Q8BPM6, Q8C627, Q8N4S0, Q8R5H6, Q91W45, Q921P9

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“HIF-1 complex”	“up-regulates quantity by expression”	BNIP3L	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of apoptotic process	6	7.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

932 predictions. Top by Δscore:

Variant	Effect	Δscore
8:26383227:AACAG:A	donor_loss	1.0000
8:26383228:ACA:A	donor_gain	1.0000
8:26383230:AG:A	donor_loss	1.0000
8:26383231:G:GG	donor_gain	1.0000
8:26383231:GTGA:G	donor_loss	1.0000
8:26391241:A:AC	acceptor_loss	1.0000
8:26391242:G:A	acceptor_loss	1.0000
8:26391422:GACAG:G	donor_gain	1.0000
8:26391424:CAG:C	donor_gain	1.0000
8:26391425:AG:A	donor_gain	1.0000
8:26391426:GG:G	donor_gain	1.0000
8:26391427:G:GA	donor_loss	1.0000
8:26391427:G:GG	donor_gain	1.0000
8:26391428:T:G	donor_loss	1.0000
8:26395224:TTCTA:T	acceptor_loss	1.0000
8:26395225:TCTAG:T	acceptor_loss	1.0000
8:26395226:CTAG:C	acceptor_loss	1.0000
8:26395227:TAG:T	acceptor_loss	1.0000
8:26395228:A:AG	acceptor_gain	1.0000
8:26395228:AGCCC:A	acceptor_loss	1.0000
8:26395229:G:GA	acceptor_gain	1.0000
8:26395229:GC:G	acceptor_gain	1.0000
8:26395229:GCC:G	acceptor_gain	1.0000
8:26395229:GCCC:G	acceptor_gain	1.0000
8:26407998:A:AG	acceptor_gain	1.0000
8:26407999:G:GA	acceptor_gain	1.0000
8:26407999:GTC:G	acceptor_gain	1.0000
8:26407999:GTCA:G	acceptor_gain	1.0000
8:26408104:G:GG	donor_gain	1.0000
8:26383191:GAAAA:G	donor_gain	0.9900

AlphaMissense

1467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:26391366:T:A	L75H	1.000
8:26391366:T:C	L75P	1.000
8:26391374:G:C	A78P	1.000
8:26408337:C:A	P191Q	1.000
8:26408370:G:A	G202E	1.000
8:26408375:G:C	G204R	1.000
8:26408376:G:A	G204D	1.000
8:26391248:T:A	W36R	0.999
8:26391248:T:C	W36R	0.999
8:26391250:G:C	W36C	0.999
8:26391250:G:T	W36C	0.999
8:26391363:T:C	I74T	0.999
8:26391363:T:G	I74S	0.999
8:26391366:T:G	L75R	0.999
8:26391379:A:C	Q79H	0.999
8:26391379:A:T	Q79H	0.999
8:26408072:T:A	W144R	0.999
8:26408072:T:C	W144R	0.999
8:26408074:G:C	W144C	0.999
8:26408074:G:T	W144C	0.999
8:26408083:A:C	R147S	0.999
8:26408083:A:T	R147S	0.999
8:26408337:C:G	P191R	0.999
8:26408343:T:C	L193P	0.999
8:26408354:C:G	H197D	0.999
8:26408355:A:G	H197R	0.999
8:26408358:T:A	V198D	0.999
8:26408364:C:A	A200D	0.999
8:26408369:G:A	G202R	0.999
8:26408369:G:C	G202R	0.999

dbSNP variants (sampled 300 via entrez): RS1000014681 (8:26412582 A>T), RS1000074983 (8:26383626 G>A,T), RS1000174677 (8:26393021 T>C), RS1000190166 (8:26389358 T>C), RS1000368597 (8:26381651 T>C), RS1000393466 (8:26395703 T>A), RS1000456750 (8:26413534 A>G), RS1000469716 (8:26412941 A>C,G), RS1000827753 (8:26395817 G>A,T), RS1000877234 (8:26387184 G>A), RS1000890664 (8:26408787 G>A), RS1000898729 (8:26405477 T>C), RS1000929543 (8:26405738 T>C), RS1001059762 (8:26410820 G>T), RS1001226919 (8:26401677 T>A)

Disease associations

OMIM: gene MIM:605368 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST003075_132	Cognitive decline rate in late mild cognitive impairment	4.000000e-07
GCST003075_90	Cognitive decline rate in late mild cognitive impairment	3.000000e-07
GCST004611_31	High light scatter reticulocyte count	1.000000e-12
GCST004612_39	High light scatter reticulocyte percentage of red cells	1.000000e-11
GCST004621_121	Red cell distribution width	9.000000e-19
GCST004628_97	Immature fraction of reticulocytes	2.000000e-25
GCST004946_17	Schizophrenia	2.000000e-11
GCST007201_38	Schizophrenia	7.000000e-06
GCST007201_400	Schizophrenia	4.000000e-07
GCST007201_95	Schizophrenia	2.000000e-12
GCST008595_196	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	7.000000e-09
GCST010703_188	Brain morphology (MOSTest)	7.000000e-11
GCST90002385_162	High light scatter reticulocyte count	2.000000e-16
GCST90002386_473	High light scatter reticulocyte percentage of red cells	1.000000e-13
GCST90002387_393	Immature fraction of reticulocytes	1.000000e-44
GCST90002389_173	Lymphocyte percentage of white cells	1.000000e-09
GCST90002390_602	Mean corpuscular hemoglobin	4.000000e-15
GCST90002391_230	Mean corpuscular hemoglobin concentration	2.000000e-13
GCST90002392_574	Mean corpuscular volume	2.000000e-09
GCST90002403_625	Red blood cell count	3.000000e-10
GCST90002404_313	Red cell distribution width	9.000000e-68

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004346	neuroimaging measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, increases expression, affects reaction, increases cleavage, affects expression (+1 more)	7
Fluorouracil	affects response to substance, decreases expression, increases expression	5
cobaltous chloride	increases expression, decreases reaction	4
Oxygen	affects binding, increases reaction, increases expression	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment	4
bisphenol A	affects expression, affects methylation, increases expression	3
(+)-JQ1 compound	increases expression	3
Air Pollutants	increases abundance, decreases expression, affects cotreatment	3
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	3
Cisplatin	affects cotreatment, affects reaction, increases lipidation, increases expression	3
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Arsenic Trioxide	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Ethanol	decreases reaction, increases expression, affects cotreatment, decreases expression, increases abundance	2
Capsaicin	decreases expression, increases expression	2
Ozone	increases abundance, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Tunicamycin	affects expression, decreases expression	2
Cyclosporine	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
PF-06840003	decreases expression, decreases reaction	1
dicrotophos	decreases expression	1
tungsten carbide	affects cotreatment, increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9YP	Ubigene HeLa BNIP3L KO	Cancer cell line	Female
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

Clinical trials (associated diseases)

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