BCL2L10

Summary

BCL2L10 (BCL2 like 10, HGNC:993) is a protein-coding gene on chromosome 15q21.2, encoding Bcl-2-like protein 10 (Q9HD36). Promotes cell survival by suppressing apoptosis induced by BAX but not BAK.

The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains conserved BH4, BH1 and BH2 domains. This protein can interact with other members of BCL-2 protein family including BCL2, BCL2L1/BCL-X(L), and BAX. Overexpression of this gene has been shown to suppress cell apoptosis possibly through the prevention of cytochrome C release from the mitochondria, and thus activating caspase-3 activation. The mouse counterpart of this protein is found to interact with Apaf1 and forms a protein complex with Caspase 9, which suggests the involvement of this protein in APAF1 and CASPASE 9 related apoptotic pathway.

Source: NCBI Gene 10017 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total — 1 likely-pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_020396

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:993
Approved symbol	BCL2L10
Name	BCL2 like 10
Location	15q21.2
Locus type	gene with protein product
Status	Approved
Aliases	Diva, Boo, BCL-B
Ensembl gene	ENSG00000137875
Ensembl biotype	protein_coding
OMIM	606910
Entrez	10017

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000260442, ENST00000561198

RefSeq mRNA: 2 — MANE Select: NM_020396 NM_001306168, NM_020396

CCDS: CCDS10148, CCDS76756

Canonical transcript exons

ENST00000260442 — 2 exons

Exon	Start	End
ENSE00000688898	52112238	52112775
ENSE00001015560	52109263	52109973

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 77.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1179 / max 22.4116, expressed in 38 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149976	0.0883	27
149975	0.0296	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	77.68	gold quality
liver	UBERON:0002107	73.54	gold quality
skin of abdomen	UBERON:0001416	73.47	gold quality
zone of skin	UBERON:0000014	72.48	gold quality
skin of leg	UBERON:0001511	71.89	gold quality
right adrenal gland	UBERON:0001233	70.72	gold quality
right adrenal gland cortex	UBERON:0035827	70.46	gold quality
left adrenal gland	UBERON:0001234	69.25	gold quality
esophagus mucosa	UBERON:0002469	69.12	gold quality
adult mammalian kidney	UBERON:0000082	68.29	gold quality
left adrenal gland cortex	UBERON:0035825	67.86	gold quality
nucleus accumbens	UBERON:0001882	67.20	gold quality
duodenum	UBERON:0002114	66.18	gold quality
vagina	UBERON:0000996	65.99	gold quality
adrenal gland	UBERON:0002369	65.52	gold quality
mucosa of transverse colon	UBERON:0004991	64.77	gold quality
lower esophagus mucosa	UBERON:0035834	64.25	gold quality
ectocervix	UBERON:0012249	64.22	gold quality
kidney	UBERON:0002113	62.90	gold quality
putamen	UBERON:0001874	62.84	gold quality
endometrium	UBERON:0001295	62.82	gold quality
caudate nucleus	UBERON:0001873	62.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	60.71	gold quality
islet of Langerhans	UBERON:0000006	60.67	gold quality
small intestine	UBERON:0002108	60.32	gold quality
gall bladder	UBERON:0002110	59.96	gold quality
cortex of kidney	UBERON:0001225	59.58	gold quality
cortical plate	UBERON:0005343	59.08	gold quality
uterine cervix	UBERON:0000002	58.54	gold quality
rectum	UBERON:0001052	58.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	1502.98
E-ANND-3	no	1.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting BCL2L10, 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-302C-5P	99.97	72.56	3642
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4447	99.85	67.81	2900
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-6844	99.82	70.69	2423
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-450A-2-3P	97.91	67.56	1459

Literature-anchored findings (GeneRIF, showing 28)

• Thus, these results indicate the existence of a previously undiscovered mechanism by which NM23-H2 involves in the regulation of Diva-mediated apoptosis. (PMID:17532299)
• distinctions in the behaviors of Bcl-B and Mcl-1 relative to the other anti-apoptotic Bcl-2 family members, where Bcl-B and Mcl-1 display reciprocal abilities to bind and neutralize Bax and Bak. (PMID:18178565)
• Tumor-specific alterations in Bcl-B expression may define subsets of nonepithelial and epithelial neoplasms with distinct clinical behaviors. (PMID:18483366)
• Interaction of endogenous proteins of BCL2L10 and HIP1R in 293T cells was determined by immunoprecipitation, and their direct association was confirmed by the Far-Western analysis. (PMID:19255499)
• BCL2L10 Is a novel and prime candidate related to oocyte maturation, fertility, and embryo developmental competence (PMID:19551325)
• BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer. (PMID:20428828)
• study evaluates 3D structure of Bcl-2L10 protein using homology modeling and aims to understand plausible functional and binding interactions between Bcl-2L10 with BH3 domain of BAX using protein - protein docking (PMID:20919753)
• The apoptotic gene BCL2L10 is a frequent target for aberrant promoter methylation in patients with acute leukemia, de novo and therapy-related. (PMID:21077739)
• Loss of BCL2L10 protein expression predicts poor clinical outcome in gastric carcinoma. (PMID:21166696)
• The pro-apoptotic effect of BCL2L10 and growth promotion by BCL2L10 siRNA in gastric cancer cells suggest that it may be a tumour suppressor. (PMID:21171085)
• BCL2L10 methylation is associated with myelodysplastic syndromes. (PMID:21760590)
• Ubqln stabilizes BCLb protein, while also promoting monoubiquitination on multiple lysine residues and relocation to the cytosol. (PMID:22233804)
• Bcl-B interacts with the BH3 domain of BECN1 and Bcl-B overexpression reduces autophagy triggered by a variety of pro-autophagic stimuli. (PMID:22498477)
• expression is predictive of azacitidine-resistance in myelodysplastic syndrome patients (PMID:22577154)
• Bcl-B in complex with the BH3 motif of Bim protected cells from Bax-dependent apoptotic pathways. (PMID:23235460)
• Data suggest that BCL2L10 is localized predominantly to mitochondria in high-quality preimplantation embryos/blastocysts; in contrast, abnormal embryos/blastocysts exhibit extra-mitochondrial localization (cytoplasm/cell nucleus) of BCL2L10. (PMID:23293224)
• polyubiquitination and proteasomal turnover dictate the expression level and anti-apoptotic capacity of Bcl-B (PMID:23563182)
• Identification of a variant in the BCL2L10 gene as a protective factor for the development of therapy-related myeloid neoplasms and de novo myelodysplastic syndrome. (PMID:24047476)
• we describe the identification of a structural genetic variant segregating with affective psychosis in a family with multiple members suffering from bipolar I disorder. Using whole-genome sequencing, we delineated the translocation breakpoints as corresponding intragenic events disrupting BCL2L10 and PNLDC1. These data warrant further consideration for BCL2L10 and PNLDC1 as novel candidates for affective psychosis. (PMID:27260655)
• Results found that BCL2L10 was down-regulated in human hepatocellular carcinoma (HCC) tissues; its overexpression suppresses cell growth and migration of HCC cell lines. These results suggested that BCL2L10 functions as a tumor-suppressor in HCC. (PMID:27770580)
• These results suggest that by inhibiting Bcl2l10 activity and promoting contact between endoplasmic reticulum and mitochondria, IRBIT facilitates massive Ca(2+) transfer to mitochondria and promotes apoptosis. (PMID:27995898)
• BCLB expression was a starvation stress sensor inducing apoptosis and autophagy simultaneously in HCC cells through the adenosine monophosphate-activated protein kinase AMPK-mTOR signaling cascade. (PMID:28259820)
• marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice. (PMID:28514758)
• BCL2L10 (Nrh protein) is localized to the endoplasmic reticulum and is a poor prognostic marker linked with chemotherapy resistance in breast cancer. (PMID:29330143)
• Bcl2l10 mediates the proliferation, invasion and migration of ovarian cancer cells. (PMID:31894274)
• Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1. (PMID:33649794)
• Nrh L11R single nucleotide polymorphism, a new prediction biomarker in breast cancer, impacts endoplasmic reticulum-dependent Ca[2+] traffic and response to neoadjuvant chemotherapy. (PMID:37391438)
• Bcl-B: an “unknown” protein of the Bcl-2 family. (PMID:37899453)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcl2l10	ENSDARG00000026766
rattus_norvegicus	Bcl2l10	ENSRNOG00000009308
caenorhabditis_elegans		WBGENE00000423

Paralogs (8): BAK1 (ENSG00000030110), BAX (ENSG00000087088), BCL2L2 (ENSG00000129473), BCL2A1 (ENSG00000140379), MCL1 (ENSG00000143384), BCL2L1 (ENSG00000171552), BCL2 (ENSG00000171791), BOK (ENSG00000176720)

Protein

Protein identifiers

Bcl-2-like protein 10 — Q9HD36 (reviewed: Q9HD36)

Alternative names: Anti-apoptotic protein Boo, Anti-apoptotic protein NrH, Apoptosis regulator Bcl-B

All UniProt accessions (2): Q9HD36, H0YMD5

UniProt curated annotations — full annotation on UniProt →

Function. Promotes cell survival by suppressing apoptosis induced by BAX but not BAK. Increases binding of AHCYL1/IRBIT to ITPR1. Reduces ITPR1-mediated calcium release from the endoplasmic reticulum cooperatively with AHCYL1/IRBIT under normal cellular conditions. Under apoptotic stress conditions, dissociates from ITPR1 and is displaced from mitochondria-associated endoplasmic reticulum membranes, leading to increased Ca(2+) transfer to mitochondria which promotes apoptosis. Required for the correct formation of the microtubule organizing center during oocyte cell division, potentially via regulation of protein abundance and localization of other microtubule organizing center components such as AURKA and TPX2.

Subunit / interactions. Interacts with BAX. Interacts with BCL2 and BCL2L1/BCLX. Interacts with APAF1. Interacts with ITPR1, ITPR2 and ITPR3; the interaction with ITPR1 is increased in the presence of AHCLY1. Interacts with AHCYL1. Interacts with HIP1R (via ENTH and I/LWEQ domains). Interacts with CASP9. Interacts with BCL2L11/BIM. Interacts with BIK. Interacts with UBQLN4. Interacts with NME2/NM23-H2. Interacts with PMAIP1/NOXA. Interacts with TPX2. Interacts with UBQLN1; in the cytoplasm. Interacts (via BH1 domain) with BECN1.

Subcellular location. Mitochondrion. Nucleus membrane. Endoplasmic reticulum. Cytoplasm. Cytoskeleton. Spindle.

Tissue specificity. Widely expressed in adult tissues. Preferentially expressed in lung, liver and kidney.

Post-translational modifications. Monoubiquitinated by UBQLN1; results in stabilization of BCL2L10 protein abundance and in relocalization from mitochondria to cytoplasm.

Similarity. Belongs to the Bcl-2 family.

RefSeq proteins (2): NP_001293097, NP_065129* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002475	Bcl2-like	Family
IPR020717	Bcl2_BH1_motif_CS	Conserved_site
IPR020726	Bcl2_BH2_motif_CS	Conserved_site
IPR026298	Bcl-2_fam	Family
IPR036834	Bcl-2-like_sf	Homologous_superfamily
IPR046371	Bcl-2_BH1-3	Domain

Pfam: PF00452

UniProt features (29 total): helix 9, mutagenesis site 8, cross-link 3, sequence conflict 2, short sequence motif 2, chain 1, transmembrane region 1, region of interest 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4B4S	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HD36-F1	84.64	0.52

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 (3): 119, 120, 128

Mutagenesis-validated functional residues (8):

Position	Phenotype
118–133	abolishes ca(2+) binding.
119	abolishes ubiquitination. no effect on localization to the mitochondria. no effect on interaction with bcl2l11, bik, bbc
120	abolishes ubiquitination. no effect on localization to the mitochondria. no effect on interaction with bcl2l11, bik, bbc
128	abolishes ubiquitination. no effect on localization to the mitochondria. no effect on interaction with bcl2l11, bik, bbc
131	abolishes ca(2+) binding; when associated with n-133.
133	abolishes ca(2+) binding; when associated with r-131.
178–191	abolishes interaction with nme2.
95	reduces interaction with becn1 and bcl2l11.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_MALE_GAMETE_GENERATION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_RELEASE_OF_CYTOCHROME_C_FROM_MITOCHONDRIA, GOBP_SIGNAL_TRANSDUCTION_IN_ABSENCE_OF_LIGAND, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_DNA_DAMAGE_RESPONSE, GOCC_MITOCHONDRIAL_ENVELOPE, TGANTCA_AP1_C, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, KIM_RESPONSE_TO_TSA_AND_DECITABINE_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_SPINDLE

GO Biological Process (11): release of cytochrome c from mitochondria (GO:0001836), apoptotic process (GO:0006915), spermatogenesis (GO:0007283), female gamete generation (GO:0007292), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), microtubule organizing center organization (GO:0031023), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), regulation of apoptotic process (GO:0042981), transmembrane transport (GO:0055085)

GO Molecular Function (4): calcium ion binding (GO:0005509), channel activity (GO:0015267), caspase binding (GO:0089720), protein binding (GO:0005515)

GO Cellular Component (11): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), spindle (GO:0005819), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), nucleus (GO:0005634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	3
cytoplasm	3
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
apoptotic signaling pathway	2
regulation of apoptotic process	2
intracellular membraneless organelle	2
apoptotic mitochondrial changes	1
programmed cell death	1
execution phase of apoptosis	1
developmental process involved in reproduction	1
male gamete generation	1
gamete generation	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
microtubule cytoskeleton organization	1
microtubule-based process	1
cellular component organization	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
signal transduction in absence of ligand	1
extrinsic apoptotic signaling pathway	1
regulation of programmed cell death	1
transport	1
cellular process	1
metal ion binding	1
passive transmembrane transporter activity	1
protease binding	1
binding	1
mitochondrial membrane	1
organelle outer membrane	1
endomembrane system	1
microtubule cytoskeleton	1
nucleus	1
nuclear envelope	1
organelle membrane	1
organelle membrane contact site	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCL2L10	BCL2L11	O43521	888
BCL2L10	BCL2L2-PABPN1	Q92843	880
BCL2L10	BCL2L1	Q07817	872
BCL2L10	BCL2A1	Q16548	848
BCL2L10	BCL2	P10415	845
BCL2L10	MCL1	Q07820	805
BCL2L10	PMAIP1	Q13794	777
BCL2L10	BOK	Q9UMX3	750
BCL2L10	HRK	O00198	718
BCL2L10	CYCS	P00001	697
BCL2L10	BAK1	Q16611	675
BCL2L10	NR4A1	P22736	651
BCL2L10	UBQLN1	Q9UMX0	636
BCL2L10	BIK	Q13323	621
BCL2L10	BMF	Q96LC9	614

IntAct

50 interactions, top by confidence:

A	B	Type	Score
BCL2L11	BAX	psi-mi:“MI:0915”(physical association)	0.940
BCL2L10	BCL2L11	psi-mi:“MI:0407”(direct interaction)	0.830
BCL2L11	BCL2L10	psi-mi:“MI:0915”(physical association)	0.830
BCL2L10	BCL2L11	psi-mi:“MI:0914”(association)	0.830
BCL2L10	BIK	psi-mi:“MI:0915”(physical association)	0.700
BIK	BCL2L10	psi-mi:“MI:0915”(physical association)	0.700
ITPR1	BCL2L10	psi-mi:“MI:0915”(physical association)	0.660
ITPR1	BCL2L10	psi-mi:“MI:0407”(direct interaction)	0.660
AHCYL1	BCL2L10	psi-mi:“MI:0915”(physical association)	0.590
BCL2L10	AHCYL1	psi-mi:“MI:0915”(physical association)	0.590
BCL2L10	BAX	psi-mi:“MI:0915”(physical association)	0.560
BCL2L10	MGST2	psi-mi:“MI:0915”(physical association)	0.560
BMF	BCL2L10	psi-mi:“MI:0915”(physical association)	0.560
SAMD4B	BCL2L10	psi-mi:“MI:0915”(physical association)	0.560
MGST2	BCL2L10	psi-mi:“MI:0915”(physical association)	0.560
TMEM200A	BCL2L10	psi-mi:“MI:0915”(physical association)	0.560
ITPR1	AHCYL1	psi-mi:“MI:0914”(association)	0.500

BioGRID (26): NR4A1 (Affinity Capture-Western), BCL2L10 (Two-hybrid), BCL2L10 (Affinity Capture-Western), BECN1 (Affinity Capture-Western), BCL2L10 (Affinity Capture-Western), BECN1 (Reconstituted Complex), BCL2L10 (Two-hybrid), BCL2L10 (Two-hybrid), BCL2L10 (Two-hybrid), BCL2L11 (Two-hybrid), TMEM200A (Two-hybrid), SAMD4B (Two-hybrid), BCL2L10 (Affinity Capture-Western), BCL2 (Affinity Capture-Western), BAX (Affinity Capture-Western)

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: O02703, P70345, P97287, Q07812, Q07813, Q07820, Q1RMX3, Q45T69, Q63690, Q7YRZ9, Q8HYS5, Q90343, Q90ZN1, Q92843, Q99M66, Q9HD36, Q9Z1P3, Q9Z0F3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 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
C-type lectin receptors (CLRs)	5	119.0×	2e-08
CLEC7A (Dectin-1) signaling	5	71.4×	1e-07
Signaling by Receptor Tyrosine Kinases	5	25.8×	3e-06
Innate Immune System	5	12.8×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of apoptotic process	6	28.4×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	32
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2665011	GRCh38/hg38 15q21.2(chr15:52095744-52533191)	Likely pathogenic

SpliceAI

335 predictions. Top by Δscore:

Variant	Effect	Δscore
15:52111988:AAG:A	donor_gain	0.9800
15:52112335:T:TA	donor_gain	0.9800
15:52109973:CCTA:C	acceptor_loss	0.9000
15:52109974:C:A	acceptor_loss	0.9000
15:52109975:TA:T	acceptor_loss	0.9000
15:52109976:A:C	acceptor_loss	0.9000
15:52112236:A:AC	donor_gain	0.9000
15:52112237:C:CC	donor_gain	0.9000
15:52109990:GAAAA:G	acceptor_loss	0.8900
15:52112237:CCCAG:C	donor_gain	0.8900
15:52109969:CCATC:C	acceptor_gain	0.8700
15:52109970:CATCC:C	acceptor_gain	0.8700
15:52112236:AC:A	donor_gain	0.8700
15:52112237:CC:C	donor_gain	0.8700
15:52112245:C:CA	donor_gain	0.8700
15:52109988:GAGAA:G	acceptor_loss	0.8600
15:52109989:AGAAA:A	acceptor_loss	0.8600
15:52109991:AAAAG:A	acceptor_loss	0.8600
15:52112232:GCTC:G	donor_loss	0.8600
15:52112233:CTCAC:C	donor_loss	0.8600
15:52112234:TCAC:T	donor_loss	0.8600
15:52112235:CA:C	donor_loss	0.8600
15:52112236:ACCC:A	donor_loss	0.8600
15:52112237:C:A	donor_loss	0.8600
15:52112372:TCC:T	donor_gain	0.8600
15:52112080:TC:T	donor_gain	0.8500
15:52112230:GTGC:G	donor_loss	0.8500
15:52112231:TGC:T	donor_loss	0.8500
15:52109986:GAGA:G	acceptor_loss	0.8400
15:52112080:T:TA	donor_gain	0.8300

AlphaMissense

1283 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:52112238:C:A	W163C	0.991
15:52112238:C:G	W163C	0.991
15:52109965:A:C	F166L	0.982
15:52109965:A:T	F166L	0.982
15:52109967:A:G	F166L	0.982
15:52112240:A:G	W163R	0.979
15:52112240:A:T	W163R	0.979
15:52112414:C:A	G105W	0.978
15:52109966:A:G	F166S	0.974
15:52112445:C:A	W94C	0.974
15:52112445:C:G	W94C	0.974
15:52112447:A:G	W94R	0.972
15:52112447:A:T	W94R	0.972
15:52112419:A:G	F103S	0.964
15:52112662:A:G	L22S	0.962
15:52112418:G:C	F103L	0.956
15:52112418:G:T	F103L	0.956
15:52112420:A:G	F103L	0.956
15:52112413:C:T	G105E	0.955
15:52112416:G:T	A104E	0.955
15:52112579:G:T	R50S	0.948
15:52112653:T:A	D25V	0.948
15:52112414:C:G	G105R	0.945
15:52112414:C:T	G105R	0.945
15:52112239:C:G	W163S	0.944
15:52112538:A:C	F63L	0.940
15:52112538:A:T	F63L	0.940
15:52112540:A:G	F63L	0.940
15:52112413:C:A	G105V	0.936
15:52112671:G:A	T19I	0.935

dbSNP variants (sampled 300 via entrez): RS1000100146 (15:52111654 G>T), RS1001396332 (15:52111185 C>A), RS1001516840 (15:52110483 G>C,T), RS1002493101 (15:52109705 C>T), RS1002525963 (15:52111679 G>A), RS1002786894 (15:52109947 G>A), RS1003445583 (15:52113820 A>G), RS1004736951 (15:52113233 T>C), RS1005088261 (15:52113070 C>A,G), RS1005345008 (15:52112862 G>C), RS1005684945 (15:52111983 G>C,T), RS1005748183 (15:52110049 G>C,T), RS1006151672 (15:52112193 G>A,T), RS1006386956 (15:52114487 A>G), RS1006723573 (15:52111094 T>C)

Disease associations

OMIM: gene MIM:606910 | 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 (2): CHEMBL5169272 (PROTEIN-PROTEIN INTERACTION), CHEMBL5988 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,718 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL408194	OBATOCLAX	3	2,914

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

Binding affinities (BindingDB)

81 measured of 81 human assays (81 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2,5-bis(chloranyl)-3-(4-methylpiperazin-1-yl)-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dione	EC50	160 nM
SMR000196363	EC50	320 nM
3-chloro-4-(3-methoxyphenoxy)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	EC50	610 nM
3-chloro-4-[(1,5-dimethyl-3-oxo-2-phenylpyrazolidin-4-yl)amino]-1-(4-methoxyphenyl)pyrrole-2,5-dione	EC50	620 nM
4-[[4-(2-methyl-3-imidazo[1,2-a]pyrimidinyl)-2-thiazolyl]amino]phenol;hydrobromide	EC50	670 nM
(2-methoxyphenyl)-[4-(2-methylimidazo[1,2-a]pyrimidin-3-yl)thiazol-2-yl]amine;hydrobromide	EC50	820 nM
MLS001001946	EC50	920 nM
(m-anisylideneamino)-([1,2,4]triazolo[3,4-a]phthalazin-6-yl)amine	EC50	980 nM
1-(3-chlorophenyl)-3-(2-pyridin-3-ylpyrimidin-4-yl)urea	EC50	1110 nM
6-(3,4-Dimethoxy-phenyl)-3-furan-2-yl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine	EC50	1210 nM
2-[[2-amino-1-(3-ethoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carbonyl]amino]-4,5,6,7-tetrahydrobenzothiophene-3-carboxylic acid methyl ester	EC50	1280 nM
N-[5-[(4-chloranylphenoxy)methyl]-1,3,4-thiadiazol-2-yl]furan-2-carboxamide	EC50	1460 nM
4-(4-carbethoxyanilino)quinazoline-2-carboxylic acid ethyl ester	EC50	1510 nM
(1,1-diketo-1,2-benzothiazol-3-yl)-methyl-[[(E)-3-phenylprop-2-enylidene]amino]amine	EC50	1940 nM
2-[[2-amino-1-(3-methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carbonyl]amino]-4,5,6,7-tetrahydrobenzothiophene-3-carboxylic acid methyl ester	EC50	1950 nM
MLS000083668	EC50	2250 nM
(1,1-diketo-1,2-benzothiazol-3-yl)-methyl-(4-pyridylmethyleneamino)amine	EC50	2440 nM
5-[[5-(5-chloranyl-2-nitro-phenyl)furan-2-yl]methylidene]-1,3-diazinane-2,4,6-trione	IC50	3330 nM
4-amino-6,7-dimethoxy-3-(2-phenylethyl)-2-quinazolinethione	EC50	3340 nM
MLS000715851	EC50	3530 nM
MLS000685782	EC50	3530 nM
MLS000030575	EC50	3570 nM
(2Z)-2-(5-fluoranyl-2-oxidanylidene-indol-3-yl)-2-(4-methyl-3H-1,3-thiazol-2-ylidene)ethanenitrile	EC50	4560 nM
MLS000390291	EC50	4670 nM
MLS000390238	EC50	5260 nM
2-[(3-pyridin-2-yl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)sulfanyl]-N-(1,3-thiazol-2-yl)acetamide	EC50	5540 nM
MLS000587395	EC50	5730 nM
6-(3,4-dimethoxyphenyl)-3-(2-pyridinyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine	EC50	6180 nM
4-chloro-3-nitro-benzoic acid [4-keto-6-[[(4-methylpyrimidin-2-yl)thio]methyl]pyran-3-yl] ester	EC50	6620 nM
1-[[2,3-bis(2-furyl)quinoxalin-6-yl]carbamoyl]isonipecotic acid ethyl ester	EC50	6650 nM
(1,1-diketo-1,2-benzothiazol-3-yl)-methyl-[(5-methyl-2-furyl)methyleneamino]amine	EC50	7380 nM
2,3-bis(2-furanyl)-N-(phenylmethyl)-6-quinoxalinecarboxamide	EC50	7440 nM
MLS000704595	EC50	7650 nM
MLS000553768	EC50	7810 nM
4-chloro-3-nitro-benzoic acid [6-[[(4,6-dimethylpyrimidin-2-yl)thio]methyl]-4-keto-pyran-3-yl] ester	EC50	8450 nM
2-[[5-(4-chlorophenyl)-4-phenyl-1,2,4-triazol-3-yl]sulfanyl]-N-[(5-methylfuran-2-yl)methylideneamino]acetamide	EC50	8450 nM
(4E)-2-methoxy-4-[([1,2,4]triazolo[3,4-a]phthalazin-6-ylhydrazo)methylidene]-1-cyclohexa-2,5-dienone	EC50	8470 nM
MLS000534769	EC50	8540 nM
4-(2-methyl-3-imidazo[1,2-a]pyrimidinyl)-N-phenyl-2-thiazolamine	EC50	8930 nM
MLS000336087	EC50	9150 nM
1-Cyclopropyl-3-(2,3-di-furan-2-yl-quinoxalin-6-yl)-urea	EC50	9260 nM
2-(3,4-dimethoxyphenyl)-N-[(4Z)-3-keto-4-(5-methyl-3H-1,3-benzoxazol-2-ylidene)cyclohexa-1,5-dien-1-yl]acetamide	EC50	10000 nM
4-(4-chlorophenyl)-3-(2-methoxyphenyl)-1H-imidazole-2-thione	EC50	11400 nM
(1E,2E)-3-phenylacrylaldehyde (1,1-dioxido-1,2-benzisothiazol-3-yl)(2-hydroxyethyl)hydrazone	EC50	11700 nM
2-[(1,1-diketo-1,2-benzothiazol-3-yl)-(4-pyridylmethyleneamino)amino]ethanol;hydrochloride	EC50	11800 nM
3-(2-methoxybenzyl)-5-[1-(4-methylbenzoyl)piperidin-4-yl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-ol	EC50	12200 nM
2-[(1,1-dioxo-1,2-benzothiazol-3-yl)-[(phenylmethylene)amino]amino]ethanol	EC50	12800 nM
2,3-bis(2-furyl)-N-homoveratryl-quinoxaline-6-carboxamide	EC50	13600 nM
(3-methyl-4-pyrrolidino-phenyl)amine;hydrochloride	EC50	13700 nM
2-[(1-prop-2-ynyl-3-indolyl)methylidene]indene-1,3-dione	EC50	13800 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.44	IC50	360	nM	EPIGALOCATECHIN GALLATE
6.18	IC50	660	nM	GAMBOGIC ACID
6.00	Ki	1000	nM	OBATOCLAX
5.74	IC50	1830	nM	CHEMBL5193844
5.51	IC50	3100	nM	CHEMBL5207007

PubChem BioAssay actives

5 with measured affinity, of 7 total; 5 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
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1858784: Inhibition of Bcl-B/Bid (unknown origin)	ic50	0.3600	uM
(Z)-4-[(1S,2S,8R,17S,19R)-12-hydroxy-8,21,21-trimethyl-5-(3-methylbut-2-enyl)-8-(4-methylpent-3-enyl)-14,18-dioxo-3,7,20-trioxahexacyclo[15.4.1.02,15.02,19.04,13.06,11]docosa-4(13),5,9,11,15-pentaen-19-yl]-2-methylbut-2-enoic acid	1938345: Displacement of fluorescein tagged BID BH3 peptide from GST-tagged recombinant Bcl-B (unknown origin) by fluorescence polarization-based competitive binding assay	ic50	0.6600	uM
(2Z)-2-[(5Z)-5-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-ylidene]indole	330738: Inhibition of BH3 peptide binding to human recombinant BCL-b by fluorescence polarization assay	ki	1.0000	uM
[(1S,2R,5S,6S,9R)-2-butyl-6-[(3-formamido-2-hydroxybenzoyl)amino]-5,9-dimethyl-3,7-dioxocyclononyl] 3-methylbutanoate	1858835: Inhibition of Bcl-B (unknown origin)/ human Bid by fluorescence polarization assay	ic50	1.8300	uM
[4-[(4,9-dioxo-3a,9a-dihydrobenzo[f][1,3]benzothiazol-2-yl)amino]phenyl] (2S)-2-(methoxycarbonylamino)-4-methylsulfanylbutanoate	1858793: Inhibition of Bcl-B/Bid (unknown origin) by fluorescence polarization assay	ic50	3.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bufotalin	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
VX-agent	increases expression	1
3,3’-diindolylmethane	increases expression	1
butyraldehyde	increases expression	1
bufalin	decreases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
3,4,5,4’-tetramethoxystilbene	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases reaction, decreases expression	1
brevetoxin 2	increases expression	1
Zoledronic Acid	affects expression	1
Air Pollutants	increases expression	1
Aldehydes	increases expression	1
Cisplatin	decreases expression, increases reaction	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Menthol	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Paraquat	decreases expression	1
Potassium Chloride	decreases response to substance, increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Dronabinol	decreases response to substance, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

8 unique, capped per target: 7 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5113854	Binding	Inhibition of Bcl-B/Bid (unknown origin)	Development of Mcl-1 inhibitors for cancer therapy. — Eur J Med Chem
CHEMBL1794518	Functional	PUBCHEM_BIOASSAY: Isothermal titration calorimetry (ITC) with Bcl-B and compounds active in primary screen. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1693]	PubChem BioAssay data set

Clinical trials (associated diseases)

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