BEND6

Summary

BEND6 (BEN domain containing 6, HGNC:20871) is a protein-coding gene on chromosome 6p12.1, encoding BEN domain-containing protein 6 (Q5SZJ8). Acts as a corepressor of recombining binding protein suppressor hairless (RBPJ) and inhibits Notch signaling in neural stem cells, thereby opposing their self-renewal and promoting neurogenesis.

Enables transcription corepressor activity. Predicted to be involved in negative regulation of Notch signaling pathway and positive regulation of neuron differentiation. Predicted to be active in nucleus.

Source: NCBI Gene 221336 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_152731

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20871
Approved symbol	BEND6
Name	BEN domain containing 6
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30162, bA203B9.1
Ensembl gene	ENSG00000151917
Ensembl biotype	protein_coding
OMIM	621217
Entrez	221336

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370745, ENST00000370746, ENST00000370748, ENST00000484701, ENST00000885664, ENST00000885665, ENST00000926046, ENST00000926047

RefSeq mRNA: 2 — MANE Select: NM_152731 NM_001318539, NM_152731

CCDS: CCDS43476, CCDS83102

Canonical transcript exons

ENST00000370746 — 7 exons

Exon	Start	End
ENSE00001811604	56955107	56955460
ENSE00001894787	57026082	57027346
ENSE00002142353	56981711	56981930
ENSE00002168008	56992378	56992555
ENSE00003511517	57018421	57018557
ENSE00003536227	57015133	57015353
ENSE00003635937	57017207	57017399

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 97.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2021 / max 94.7777, expressed in 945 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68315	2.2783	762
68317	0.2948	129
68312	0.2583	156
68313	0.2088	111
68314	0.0851	20
68316	0.0368	13
204033	0.0299	10
204032	0.0100	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.88	gold quality
primary visual cortex	UBERON:0002436	94.80	gold quality
cerebellar vermis	UBERON:0004720	94.57	gold quality
cerebellar cortex	UBERON:0002129	93.98	gold quality
cerebellar hemisphere	UBERON:0002245	93.92	gold quality
pons	UBERON:0000988	93.70	gold quality
cerebellum	UBERON:0002037	93.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.95	gold quality
occipital lobe	UBERON:0002021	92.88	gold quality
prefrontal cortex	UBERON:0000451	91.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.02	gold quality
anterior cingulate cortex	UBERON:0009835	90.17	gold quality
frontal cortex	UBERON:0001870	89.91	gold quality
neocortex	UBERON:0001950	89.78	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.67	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.28	gold quality
right frontal lobe	UBERON:0002810	89.25	gold quality
cerebral cortex	UBERON:0000956	88.94	gold quality
cortical plate	UBERON:0005343	88.01	gold quality
middle temporal gyrus	UBERON:0002771	87.50	gold quality
postcentral gyrus	UBERON:0002581	87.49	gold quality
parietal lobe	UBERON:0001872	87.40	gold quality
superior frontal gyrus	UBERON:0002661	87.39	gold quality
amygdala	UBERON:0001876	86.99	gold quality
hypothalamus	UBERON:0001898	86.82	gold quality
caudate nucleus	UBERON:0001873	86.39	gold quality
nucleus accumbens	UBERON:0001882	86.37	gold quality
Ammon’s horn	UBERON:0001954	86.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.47
E-GEOD-124858	no	135.47
E-CURD-10	no	90.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting BEND6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-466	99.67	70.85	2863

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bend6	ENSMUSG00000042182
rattus_norvegicus	Bend6	ENSRNOG00000052376

Protein

Protein identifiers

BEN domain-containing protein 6 — Q5SZJ8 (reviewed: Q5SZJ8)

All UniProt accessions (2): Q5SZJ8, Q5SZK0

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a corepressor of recombining binding protein suppressor hairless (RBPJ) and inhibits Notch signaling in neural stem cells, thereby opposing their self-renewal and promoting neurogenesis.

Subunit / interactions. Interacts (via BEN domain) with RBPJ.

Subcellular location. Nucleus.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5SZJ8-1	1	yes
Q5SZJ8-2	2
Q5SZJ8-3	3
Q5SZJ8-4	4

RefSeq proteins (2): NP_001305468, NP_689944* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018379	BEN_domain	Domain
IPR037496	BEND6-like	Family

Pfam: PF10523

UniProt features (20 total): splice variant 6, helix 5, compositionally biased region 3, region of interest 2, chain 1, domain 1, strand 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7YUL	X-RAY DIFFRACTION	1.82
7YUN	X-RAY DIFFRACTION	2.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SZJ8-F1	72.39	0.46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 135 (showing top): HNF3ALPHA_Q6, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_NEGATIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, chr6p12, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, RIGGI_EWING_SARCOMA_PROGENITOR_DN, WTGAAAT_UNKNOWN, HFH4_01, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, TGANTCA_AP1_C, GOBP_REGULATION_OF_NOTCH_SIGNALING_PATHWAY

GO Biological Process (6): nervous system development (GO:0007399), positive regulation of neuron differentiation (GO:0045666), negative regulation of Notch signaling pathway (GO:0045746), regulation of gene expression (GO:0010468), negative regulation of macromolecule biosynthetic process (GO:0010558), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (3): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of macromolecule biosynthetic process	2
system development	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
negative regulation of signal transduction	1
gene expression	1
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
negative regulation of macromolecule metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
nucleic acid binding	1
binding	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BEND6	BEND5	Q7L4P6	685
BEND6	BEND7	Q8N7W2	649
BEND6	RBPJ	Q06330	506
BEND6	BANP	Q8N9N5	445
BEND6	BEND2	Q8NDZ0	433
BEND6	NACC2	Q96BF6	431
BEND6	LRRC58	Q96CX6	416
BEND6	NACC1	Q96RE7	398
BEND6	HMGN5	P82970	395
BEND6	SH2D5	Q6ZV89	392
BEND6	ZNF414	Q96IQ9	367
BEND6	APBB1	O00213	364
BEND6	CASKIN2	Q8WXE0	361
BEND6	METTL27	Q8N6F8	355
BEND6	BEND3	Q5T5X7	353

IntAct

5 interactions, top by confidence:

A	B	Type	Score
BEND6	LTO1	psi-mi:“MI:0915”(physical association)	0.400
BEND6		psi-mi:“MI:0915”(physical association)	0.370
OR13G1	VPS26C	psi-mi:“MI:0914”(association)	0.350
MED29	SSNA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): BEND6 (Negative Genetic), BEND6 (Affinity Capture-MS), ORAOV1 (Affinity Capture-MS), BEND6 (Affinity Capture-MS), TFAM (Cross-Linking-MS (XL-MS)), BEND6 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A4IGQ8, B0BLU1, B5XCB8, O75113, O75132, P14629, Q0IIM1, Q0V8G8, Q17RS7, Q1JPT7, Q1RMM0, Q28GK6, Q28J92, Q3T0G1, Q4R3Q6, Q4R7M0, Q4V7W2, Q5FWF4, Q5NVM3, Q5QJC4, Q5RCE4, Q5SZJ8, Q5U208, Q5U560, Q5ZHN5, Q6A037, Q6DDT6, Q6DIN8, Q6INS5, Q6IR68, Q6NZP1, Q6PFX2, Q6TGZ4, Q7Z6K1, Q7ZYM8, Q80XJ2, Q86VD1, Q8BMI4, Q8BZ05, Q8C4P0

Diamond homologs: Q5SZJ8, Q6PFX2

SIGNOR signaling

0 interactions.

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	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1651 predictions. Top by Δscore:

Variant	Effect	Δscore
6:56992377:GA:G	acceptor_gain	1.0000
6:56992377:GAGA:G	acceptor_gain	1.0000
6:57015131:A:AG	acceptor_gain	1.0000
6:57015132:G:GG	acceptor_gain	1.0000
6:57015132:GT:G	acceptor_gain	1.0000
6:57015350:ACAGG:A	donor_loss	1.0000
6:57015352:AGG:A	donor_loss	1.0000
6:57015354:GTC:G	donor_loss	1.0000
6:57017205:A:AG	acceptor_gain	1.0000
6:57017206:G:GG	acceptor_gain	1.0000
6:57017367:C:G	donor_gain	1.0000
6:57017381:G:GT	donor_gain	1.0000
6:56955456:GCCGG:G	donor_gain	0.9900
6:56992372:TTTTA:T	acceptor_loss	0.9900
6:56992373:TTTA:T	acceptor_loss	0.9900
6:56992374:TTA:T	acceptor_loss	0.9900
6:56992375:TA:T	acceptor_loss	0.9900
6:56992375:TAGAG:T	acceptor_gain	0.9900
6:56992376:A:AG	acceptor_gain	0.9900
6:56992376:AGAGA:A	acceptor_gain	0.9900
6:56992377:G:GG	acceptor_gain	0.9900
6:56992377:GAGAG:G	acceptor_gain	0.9900
6:56992551:TCAAG:T	donor_loss	0.9900
6:56992552:CAAG:C	donor_loss	0.9900
6:56992553:AAGG:A	donor_loss	0.9900
6:56992554:AGG:A	donor_loss	0.9900
6:56992556:GTA:G	donor_loss	0.9900
6:56992557:T:A	donor_loss	0.9900
6:57014526:G:GG	donor_gain	0.9900
6:57015128:TTTA:T	acceptor_loss	0.9900

AlphaMissense

1854 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:57017262:T:C	F192S	1.000
6:57017269:T:A	N194K	1.000
6:57017269:T:G	N194K	1.000
6:57017277:T:G	M197R	1.000
6:57017315:A:C	S210R	1.000
6:57017317:C:A	S210R	1.000
6:57017317:C:G	S210R	1.000
6:57017319:T:A	L211Q	1.000
6:57017324:G:A	G213R	1.000
6:57017324:G:C	G213R	1.000
6:57017324:G:T	G213W	1.000
6:57017325:G:A	G213E	1.000
6:57017325:G:T	G213V	1.000
6:57018467:G:C	R253S	1.000
6:57018467:G:T	R253S	1.000
6:57018485:G:C	K259N	1.000
6:57018485:G:T	K259N	1.000
6:57018487:T:C	L260P	1.000
6:57018491:C:A	N261K	1.000
6:57018491:C:G	N261K	1.000
6:57018494:C:A	N262K	1.000
6:57018494:C:G	N262K	1.000
6:57017237:T:C	C184R	0.999
6:57017257:G:C	Q190H	0.999
6:57017257:G:T	Q190H	0.999
6:57017271:A:T	D195V	0.999
6:57017274:T:C	L196S	0.999
6:57017277:T:A	M197K	0.999
6:57017277:T:C	M197T	0.999
6:57017288:T:G	Y201D	0.999

dbSNP variants (sampled 300 via entrez): RS1000039079 (6:56995746 A>G,T), RS1000069823 (6:56972379 G>A), RS1000126666 (6:57026151 C>A,T), RS1000169751 (6:57016963 A>G), RS1000258426 (6:57022130 T>C,G), RS1000289731 (6:57022383 A>G), RS1000321004 (6:56998618 A>G), RS1000326993 (6:56954856 T>C), RS1000352284 (6:56998206 G>A,C), RS1000361297 (6:56963996 A>G), RS1000375504 (6:56990500 G>A), RS1000399352 (6:56983552 C>T), RS1000428915 (6:56959034 A>G), RS1000430560 (6:56983210 G>A), RS1000453239 (6:56982196 C>T)

Disease associations

OMIM: gene MIM:621217 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002541_23	Menarche (age at onset)	8.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
mercuric bromide	affects cotreatment, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Cisplatin	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	affects expression	1
butyraldehyde	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
(+)-JQ1 compound	increases expression	1
Temozolomide	decreases expression	1
Vorinostat	increases expression	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
Oxygen	decreases expression	1

Clinical trials (associated diseases)

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