BNIPL

Summary

BNIPL (BCL2 interacting protein like, HGNC:16976) is a protein-coding gene on chromosome 1q21.3, encoding Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein (Q7Z465). May be a bridge molecule between BCL2 and ARHGAP1/CDC42 in promoting cell death.

The protein encoded by this gene interacts with several other proteins, such as BCL2, ARHGAP1, MIF and GFER. It may function as a bridge molecule between BCL2 and ARHGAP1/CDC42 in promoting cell death. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 149428 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 52 total — 1 pathogenic
• MANE Select transcript: NM_138278

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16976
Approved symbol	BNIPL
Name	BCL2 interacting protein like
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	BNIPl-1, BNIPL-2, PP753, BNIP-S, BNIP-Salpha, BNIP-Sbeta
Ensembl gene	ENSG00000163141
Ensembl biotype	protein_coding
OMIM	611275
Entrez	149428

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000295294, ENST00000361277, ENST00000368931, ENST00000392802, ENST00000485855, ENST00000491386, ENST00000650563, ENST00000912274

RefSeq mRNA: 2 — MANE Select: NM_138278 NM_001159642, NM_138278

CCDS: CCDS53362, CCDS978

Canonical transcript exons

ENST00000368931 — 10 exons

Exon	Start	End
ENSE00001071985	151043332	151043434
ENSE00001150425	151042956	151043138
ENSE00001185627	151043596	151043727
ENSE00001778113	151037567	151037662
ENSE00001818563	151036586	151036766
ENSE00003482538	151045797	151045883
ENSE00003497694	151038796	151039026
ENSE00003533085	151046067	151046165
ENSE00003655467	151038504	151038568
ENSE00003835903	151046651	151047720

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 98.96.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3600 / max 202.1951, expressed in 252 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5177	1.2625	244
5176	0.0975	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.96	gold quality
upper arm skin	UBERON:0004263	98.55	gold quality
skin of abdomen	UBERON:0001416	97.93	gold quality
amniotic fluid	UBERON:0000173	97.81	gold quality
skin of leg	UBERON:0001511	97.53	gold quality
zone of skin	UBERON:0000014	97.02	gold quality
esophagus mucosa	UBERON:0002469	96.81	gold quality
upper leg skin	UBERON:0004262	96.39	gold quality
esophagus squamous epithelium	UBERON:0006920	95.39	gold quality
skin of hip	UBERON:0001554	94.35	gold quality
gingival epithelium	UBERON:0001949	93.81	gold quality
gingiva	UBERON:0001828	93.53	gold quality
oral cavity	UBERON:0000167	91.74	gold quality
pharyngeal mucosa	UBERON:0000355	91.49	gold quality
buccal mucosa cell	CL:0002336	91.22	gold quality
penis	UBERON:0000989	90.49	gold quality
mammalian vulva	UBERON:0000997	90.26	gold quality
vagina	UBERON:0000996	90.00	gold quality
nipple	UBERON:0002030	85.62	gold quality
mouth mucosa	UBERON:0003729	84.26	gold quality
palpebral conjunctiva	UBERON:0001812	83.96	gold quality
minor salivary gland	UBERON:0001830	82.77	gold quality
right lobe of thyroid gland	UBERON:0001119	80.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.41	gold quality
oviduct epithelium	UBERON:0004804	79.71	gold quality
saliva-secreting gland	UBERON:0001044	78.76	gold quality
left lobe of thyroid gland	UBERON:0001120	78.35	gold quality
body of tongue	UBERON:0011876	77.97	gold quality
prostate gland	UBERON:0002367	77.83	gold quality
thyroid gland	UBERON:0002046	77.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.74

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 7)

• These results indicate the presence of two BNIP-S splicing variants as cellular regulators and that the BCH domain of BNIP-Salpha confers a novel apoptotic function. The significance of this is discussed (PMID:11741952)
• interaction with cell proliferation-related proteins, MIF and GFER (PMID:12681488)
• BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis. (PMID:12901880)
• Data suggest that Bcl-2/adenovirus E1B 19 ku interacting protein 2-like (BNIPL-2) may regulate apoptosis through changes in the expression of genes associated with cell apoptosis, growth inhibition and cell proliferation. (PMID:15112343)
• p16INK4, IL-12, TRAIL & lymphotoxin beta gene involved in growth suppression or cell apoptosis were up-regulated & PTEN was down-regulated by BNIPL-1;suggests that it might inhibit cell growth though cell cycle arrest &/or apoptotic cell death pathway(s) (PMID:16143817)
• The present study not only suggested that BNIPL2 may be a potential biomarker of CRC but also indicated that BNIPL2 regulates CRC cancer proliferation via CD44, which could be a diagnostic and clinical treatment target. (PMID:31485655)
• BNIPL is a promising biomarker of laryngeal cancer: novel insights from bioinformatics analysis and experimental validation. (PMID:38302910)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bnipl	ENSDARG00000060435
mus_musculus	Bnipl	ENSMUSG00000028115
rattus_norvegicus	Bnipl	ENSRNOG00000021116
drosophila_melanogaster	CG11593	FBGN0035488

Paralogs (3): PRUNE2 (ENSG00000106772), BNIP2 (ENSG00000140299), ATCAY (ENSG00000167654)

Protein

Protein identifiers

Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein — Q7Z465 (reviewed: Q7Z465)

All UniProt accessions (3): A2A492, Q7Z465, F8W685

UniProt curated annotations — full annotation on UniProt →

Function. May be a bridge molecule between BCL2 and ARHGAP1/CDC42 in promoting cell death.

Subunit / interactions. Homodimer. Interacts with BCL2, ARHGAP1, MIF and GFER.

Tissue specificity. Isoform 2 is expressed in placenta and lung.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z465-1	1, BNIPL-2	yes
Q7Z465-2	2, BNIPL-1, BNIP-Salpha
Q7Z465-3	3, BNIP-Sbeta

RefSeq proteins (2): NP_001153114, NP_612122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001251	CRAL-TRIO_dom	Domain
IPR022181	Bcl2-/adenovirus-E1B	Family
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily

Pfam: PF12496, PF13716

UniProt features (11 total): compositionally biased region 4, sequence variant 2, splice variant 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z465-F1	68.67	0.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): GOBP_GROWTH, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, IRF1_Q6, GOBP_REGULATION_OF_GROWTH, chr1q21, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_ES_LCP_WITH_H3K4ME3, GOBP_REGULATION_OF_GROWTH_RATE, ESC_J1_UP_EARLY.V1_UP, ESC_V6.5_UP_LATE.V1_DN, SUPT16H_TARGET_GENES, MIR7977, MIR520E_5P, MIR3616_3P, MIR711

GO Biological Process (3): apoptotic process (GO:0006915), negative regulation of cell population proliferation (GO:0008285), regulation of growth rate (GO:0040009)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of growth	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BNIPL	BCL2	P10415	800
BNIPL	ANXA5	P08758	762
BNIPL	CDC42	P21181	683
BNIPL	GFER	P55789	662
BNIPL	RHOA	P06749	653
BNIPL	ARHGAP1	Q07960	602
BNIPL	TP53BP2	Q13625	490
BNIPL	BCL2L1	Q07817	489
BNIPL	DCP1B	Q8IZD4	481
BNIPL	KLHL8	Q9P2G9	480
BNIPL	ARHGEF1	Q92888	479
BNIPL	BIK	Q13323	472
BNIPL	STX18	Q9P2W9	452
BNIPL	CRABP2	P29373	443
BNIPL	CTU2	Q2VPK5	437

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GFER	BNIPL	psi-mi:“MI:0915”(physical association)	0.370
BNIPL	MIF	psi-mi:“MI:0915”(physical association)	0.370
BNIPL	NME2	psi-mi:“MI:0915”(physical association)	0.370
PYCR1	BNIPL	psi-mi:“MI:0915”(physical association)	0.370
PXDN	BNIPL	psi-mi:“MI:0915”(physical association)	0.370
RECQL5	BNIPL	psi-mi:“MI:0915”(physical association)	0.370
SNAPIN	BNIPL	psi-mi:“MI:0915”(physical association)	0.370
FKBP8	BNIPL	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (24): BNIPL (Reconstituted Complex), BNIPL (Two-hybrid), ARHGAP1 (Two-hybrid), BNIP2 (Two-hybrid), BCL2L1 (Two-hybrid), BNIPL (Affinity Capture-Western), BCL2 (Affinity Capture-Western), GFER (Two-hybrid), MIF (Two-hybrid), MIF (Reconstituted Complex), GFER (Reconstituted Complex), MIF (Affinity Capture-Western), GFER (Affinity Capture-Western), ALDOC (Cross-Linking-MS (XL-MS)), ALDOA (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0AV02, A2A6C4, E9PY61, G3HQ82, O95382, P04920, P23347, P35523, P35524, P40682, P70606, Q07175, Q148L1, Q498W5, Q49LS1, Q49LS3, Q5GH66, Q5PQL3, Q5RD44, Q5T1A1, Q5VW38, Q5ZJY9, Q60943, Q640M6, Q64347, Q6P6V6, Q6UX68, Q76MJ5, Q78IQ7, Q7TNJ2, Q7Z465, Q8BGI5, Q8BSD4, Q8CIP5, Q8CJI3, Q8IUH8, Q8VI23, Q8WTR4, Q91V24, Q91WD0

Diamond homologs: O54940, P85298, Q07960, Q0IHU9, Q12982, Q1M168, Q52KR3, Q54TH9, Q55AR6, Q5BJR4, Q5FWK3, Q5R4Q8, Q7Z465, Q86WG3, Q8BHE3, Q8WUY3, Q99JU7, Q9CXP4, Q9GKT0, Q9VTU3, A4IF90, A6NI28, A7T167, B2RQE8, B2RTY4, B2RWW0, B9VTT2, D3ZFJ3, D3ZZN9, E7EZG2, E7F3F0, F1LQX4, O14014, O43182, O54834, O94988, P34288, P35688, P42331, P55194

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
813322	GRCh37/hg19 1q21.3(chr1:150990288-151016203)	Pathogenic

SpliceAI

1232 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151037552:T:TA	acceptor_gain	1.0000
1:151037553:G:A	acceptor_gain	1.0000
1:151038499:TCTA:T	acceptor_loss	1.0000
1:151038500:CTA:C	acceptor_loss	1.0000
1:151038501:TAG:T	acceptor_loss	1.0000
1:151038502:A:AG	acceptor_gain	1.0000
1:151038503:G:GG	acceptor_gain	1.0000
1:151038503:GATT:G	acceptor_gain	1.0000
1:151038567:AGGTA:A	donor_loss	1.0000
1:151038568:GGTA:G	donor_loss	1.0000
1:151038569:GTAG:G	donor_loss	1.0000
1:151038570:T:G	donor_loss	1.0000
1:151039023:G:GT	donor_gain	1.0000
1:151039023:G:T	donor_gain	1.0000
1:151039024:A:T	donor_gain	1.0000
1:151046065:A:AG	acceptor_gain	1.0000
1:151046066:G:GA	acceptor_gain	1.0000
1:151046066:GTTCC:G	acceptor_gain	1.0000
1:151046162:GACA:G	donor_gain	1.0000
1:151046166:G:GG	donor_gain	1.0000
1:151037659:CTAG:C	donor_loss	0.9900
1:151037660:TAGG:T	donor_loss	0.9900
1:151037661:AGG:A	donor_loss	0.9900
1:151037662:GGTGA:G	donor_loss	0.9900
1:151037663:G:A	donor_loss	0.9900
1:151037664:T:A	donor_loss	0.9900
1:151038502:AGATT:A	acceptor_gain	0.9900
1:151038503:GA:G	acceptor_gain	0.9900
1:151038503:GAT:G	acceptor_gain	0.9900
1:151038503:GATTG:G	acceptor_gain	0.9900

AlphaMissense

2285 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151045829:T:A	V295D	0.984
1:151043646:T:A	V257D	0.983
1:151045805:A:T	K287I	0.983
1:151043386:C:A	P224H	0.981
1:151046074:T:C	F316L	0.976
1:151046076:C:A	F316L	0.976
1:151046076:C:G	F316L	0.976
1:151046084:A:T	K319I	0.974
1:151043693:T:A	W273R	0.971
1:151043693:T:C	W273R	0.971
1:151046075:T:C	F316S	0.968
1:151045826:T:A	V294D	0.966
1:151043385:C:A	P224T	0.959
1:151043386:C:G	P224R	0.959
1:151043695:G:C	W273C	0.959
1:151043695:G:T	W273C	0.959
1:151043385:C:T	P224S	0.957
1:151043064:T:C	F181S	0.956
1:151045811:T:C	L289P	0.954
1:151043063:T:C	F181L	0.953
1:151043065:C:A	F181L	0.953
1:151043065:C:G	F181L	0.953
1:151046159:T:A	V344D	0.953
1:151043383:T:C	L223P	0.951
1:151043613:T:C	L246P	0.951
1:151043652:T:C	L259S	0.950
1:151046085:A:C	K319N	0.949
1:151046085:A:T	K319N	0.949
1:151043428:T:C	L238S	0.948
1:151043636:T:G	Y254D	0.947

dbSNP variants (sampled 300 via entrez): RS1000158756 (1:151042241 T>C,G), RS1000185357 (1:151036047 C>T), RS1000528754 (1:151040441 A>T), RS1000588042 (1:151047699 G>A,C), RS1000992955 (1:151037244 T>C,G), RS1001111405 (1:151044048 G>A), RS1001206746 (1:151037471 A>G), RS1001215493 (1:151040815 A>C,G), RS1001357259 (1:151036621 C>A,T), RS1001445208 (1:151036998 T>A,C), RS1001643447 (1:151043030 G>A), RS1001885299 (1:151037782 C>G,T), RS1001893515 (1:151036380 G>A,C), RS1002214386 (1:151046467 G>A), RS1002492959 (1:151037715 G>A,T)

Disease associations

OMIM: gene MIM:611275 | disease phenotypes: MIM:617481

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (MONDO:0060490)

Orphanet (1): PRUNE1-related neurological syndrome (Orphanet:544469)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000649_7	Chronic kidney disease	1.000000e-12
GCST005951_38	Body mass index	4.000000e-09
GCST009379_19	Type 2 diabetes	9.000000e-09
GCST009379_20	Type 2 diabetes	9.000000e-09
GCST012322_10	Triglyceride levels x SSRI defined daily dose interaction in schizophrenia or bipolar disorder	4.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0005658	response to selective serotonin reuptake inhibitor

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
trichostatin A	affects cotreatment, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
mercuric bromide	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, increases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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