BEND2

Summary

BEND2 (BEN domain containing 2, HGNC:28509) is a protein-coding gene on chromosome Xp22.13, encoding BEN domain-containing protein 2 (Q8NDZ0).

This gene encodes a protein which has two BEN domains in the C-terminus. These domains are found in proteins which participate in protein and DNA interactions which occur during chromatin restructuring or transcription. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 139105 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 145 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_153346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28509
Approved symbol	BEND2
Name	BEN domain containing 2
Location	Xp22.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC33653
Ensembl gene	ENSG00000177324
Ensembl biotype	protein_coding
OMIM	301150
Entrez	139105

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000380030, ENST00000380033

RefSeq mRNA: 2 — MANE Select: NM_153346 NM_001184767, NM_153346

CCDS: CCDS14184, CCDS55375

Canonical transcript exons

ENST00000380033 — 14 exons

Exon	Start	End
ENSE00001275419	18180510	18180650
ENSE00001275427	18213774	18213911
ENSE00001275440	18171001	18171204
ENSE00001275447	18174030	18174258
ENSE00001275456	18175972	18176093
ENSE00001275464	18177569	18177769
ENSE00001275477	18191001	18191108
ENSE00001275482	18195296	18195442
ENSE00001275491	18201815	18201940
ENSE00001275496	18203501	18203915
ENSE00001275501	18212565	18212680
ENSE00001275532	18216521	18216733
ENSE00001483489	18162931	18165223
ENSE00001910301	18220726	18220886

Expression profiles

Bgee: expression breadth broad, 30 present calls, max score 86.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0201 / max 21.6521, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198587	0.0102	3
198586	0.0099	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	86.19	gold quality
leukocyte	CL:0000738	84.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.56	gold quality
blood	UBERON:0000178	64.40	gold quality
right testis	UBERON:0004534	63.41	gold quality
testis	UBERON:0000473	63.19	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.88	gold quality
left testis	UBERON:0004533	60.91	gold quality
granulocyte	CL:0000094	60.89	gold quality
lower lobe of lung	UBERON:0008949	59.86	silver quality
superficial temporal artery	UBERON:0001614	59.27	gold quality
trabecular bone tissue	UBERON:0002483	58.69	silver quality
epithelium of nasopharynx	UBERON:0001951	57.97	gold quality
bone marrow cell	CL:0002092	57.28	gold quality
bone marrow	UBERON:0002371	55.47	silver quality
amniotic fluid	UBERON:0000173	55.15	gold quality
myocardium	UBERON:0002349	55.09	gold quality
sperm	CL:0000019	54.84	gold quality
oocyte	CL:0000023	54.62	gold quality
esophagus squamous epithelium	UBERON:0006920	53.31	gold quality
cartilage tissue	UBERON:0002418	53.21	gold quality
Brodmann (1909) area 23	UBERON:0013554	53.05	gold quality
nasal cavity epithelium	UBERON:0005384	51.80	gold quality
middle temporal gyrus	UBERON:0002771	51.69	gold quality
gingival epithelium	UBERON:0001949	51.47	gold quality
caput epididymis	UBERON:0004358	51.29	gold quality
adult organism	UBERON:0007023	50.51	gold quality
corpus epididymis	UBERON:0004359	49.99	gold quality
cauda epididymis	UBERON:0004360	49.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.23
E-ENAD-27	no	15.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting BEND2, 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-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-5003-3P	99.85	69.29	2517
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-4799-5P	99.82	70.60	2663
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4690-5P	99.65	66.24	813

Literature-anchored findings (GeneRIF, showing 3)

• Spinal cord astroblastoma with an EWSR1-BEND2 fusion classified as a high-grade neuroepithelial tumour with MN1 alteration. (PMID:31863478)
• EWSR1-BEND2 fusion defines an epigenetically distinct subtype of astroblastoma. (PMID:34825267)
• Early ependymal tumor with MN1-BEND2 fusion: a mostly cerebral tumor of female children with a good prognosis that is distinct from classical astroblastoma. (PMID:36604386)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	selenon	ENSDARG00000033616
danio_rerio	zgc:113423	ENSDARG00000058978
mus_musculus	Bend2	ENSMUSG00000108981
rattus_norvegicus	AABR07037896.1	ENSRNOG00000058952

Paralogs (2): SELENON (ENSG00000162430), HOATZ (ENSG00000183644)

Protein

Protein identifiers

BEN domain-containing protein 2 — Q8NDZ0 (reviewed: Q8NDZ0)

All UniProt accessions (1): Q8NDZ0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NDZ0-1	1	yes
Q8NDZ0-2	2

RefSeq proteins (2): NP_001171696, NP_699177* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018379	BEN_domain	Domain

Pfam: PF10523

UniProt features (16 total): region of interest 4, compositionally biased region 3, domain 2, splice variant 2, sequence variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDZ0-F1	49.94	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): chrXp22, ZNF146_TARGET_GENES, ZNF8_TARGET_GENES, MIR340_5P, MIR656_3P, MIR3910, MIR5003_3P, MIR450A_1_3P, MIR7113_5P, MIR371A_5P, MIR513B_3P, MIR190B_3P, MIR4468, MIR5587_5P, MIR141_5P

GO Biological Process (0):

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BEND2	MN1	Q10571	687
BEND2	BANP	Q8N9N5	570
BEND2	BEND4	Q6ZU67	530
BEND2	BEND5	Q7L4P6	507
BEND2	CXXC5	Q7LFL8	448
BEND2	BEND6	Q5SZJ8	433
BEND2	MAGEB17	A8MXT2	429
BEND2	ZNF195	O14628	407
BEND2	ZNF850	A8MQ14	403
BEND2	NEK4	P51957	400
BEND2	ZNF394	Q53GI3	398
BEND2	RAI2	Q9Y5P3	398
BEND2	ZFTA	C9JLR9	397
BEND2	EWSR1	Q01844	394
BEND2	CMC2	Q9NRP2	371

IntAct

21 interactions, top by confidence:

A	B	Type	Score
BEND2	ANAPC11	psi-mi:“MI:0915”(physical association)	0.560
BEND2	ZMYM6	psi-mi:“MI:0915”(physical association)	0.560
ANAPC11	BEND2	psi-mi:“MI:0915”(physical association)	0.560
PRR20D	BEND2	psi-mi:“MI:0915”(physical association)	0.560
SF3A2	BEND2	psi-mi:“MI:0915”(physical association)	0.560
LHX2	BEND2	psi-mi:“MI:0915”(physical association)	0.560
ZMYM6	BEND2	psi-mi:“MI:0915”(physical association)	0.560
BEND2	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	BEND2	psi-mi:“MI:0915”(physical association)	0.370
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
BEND2	PRR20D	psi-mi:“MI:0915”(physical association)	0.000
BEND2	SF3A2	psi-mi:“MI:0915”(physical association)	0.000
BEND2	LHX2	psi-mi:“MI:0915”(physical association)	0.000
BEND2	ATXN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): BEND2 (Two-hybrid), BEND2 (Two-hybrid), BEND2 (Two-hybrid), BEND2 (Two-hybrid), PRR20B (Two-hybrid), PRR20A (Two-hybrid), PRR20D (Two-hybrid), PRR20C (Two-hybrid), PRR20E (Two-hybrid), BEND2 (Two-hybrid), APP (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GTS1, A0A1B0GWH4, A1A4L6, A1YGI6, A6NDR6, B8QB46, F1MJR8, F1QDF8, O35892, O35893, P09015, P15036, P15037, P23497, P52729, P59598, Q32NH9, Q3KRF1, Q3UM89, Q4G112, Q4V7E1, Q5M7N6, Q5ND04, Q5XIV2, Q5ZHX5, Q66IG8, Q6P1R3, Q6PCX9, Q6PJQ5, Q708W2, Q76I76, Q76I79, Q76N89, Q7M6U3, Q8AXQ4, Q8BVK9, Q8IUE0, Q8IUE1, Q8IWB6, Q8IXJ9

Diamond homologs: A0A096LPI5, A6NIU2, A6NJG6, F2Z398, P0DTE4, P51957, Q09FC8, Q5H9K5, Q5T7P6, Q68CZ1, Q6B4Z3, Q6UX73, Q86U02, Q8IV13, Q8N7M2, Q8N9N2, Q8NDZ0, Q8NEM8, Q8TDM0, Q92918, Q96J02, Q96MD7, Q9BUA6, Q9NXG0, O14607, O14628, O15054, O15550, O70546, P79457, Q5NCY0, Q8N769, A7MCS3, Q3UST5, Q3ZCU0, Q8IUI4, Q08DX0, Q8TEQ0, Q9D3S3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	73
Likely benign	17
Benign	5

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
584356	NC_000023.10:g.(?17393861)(18671684_?)del	Pathogenic
2685694	GRCh37/hg19 Xp22.13(chrX:18235875-18523090)x1	Likely pathogenic

SpliceAI

2683 predictions. Top by Δscore:

Variant	Effect	Δscore
X:18171016:T:C	donor_gain	1.0000
X:18171071:TTGG:T	donor_gain	1.0000
X:18171201:TAGC:T	acceptor_gain	1.0000
X:18171202:AGCCT:A	acceptor_loss	1.0000
X:18171204:CCTAG:C	acceptor_loss	1.0000
X:18171205:C:CA	acceptor_loss	1.0000
X:18171205:C:CC	acceptor_gain	1.0000
X:18171206:T:A	acceptor_loss	1.0000
X:18174023:AACT:A	donor_loss	1.0000
X:18174028:A:AC	donor_gain	1.0000
X:18174028:ACT:A	donor_gain	1.0000
X:18174028:ACTC:A	donor_gain	1.0000
X:18174029:C:CC	donor_gain	1.0000
X:18174029:CT:C	donor_gain	1.0000
X:18174029:CTC:C	donor_gain	1.0000
X:18174029:CTCC:C	donor_gain	1.0000
X:18174029:CTCCA:C	donor_gain	1.0000
X:18174031:C:CA	donor_gain	1.0000
X:18174262:T:TC	acceptor_gain	1.0000
X:18175970:A:AC	donor_gain	1.0000
X:18175971:C:CT	donor_gain	1.0000
X:18176090:TATT:T	acceptor_gain	1.0000
X:18177564:CATA:C	donor_loss	1.0000
X:18177565:ATACC:A	donor_loss	1.0000
X:18177566:TACC:T	donor_loss	1.0000
X:18177568:C:CT	donor_loss	1.0000
X:18177568:CCT:C	donor_gain	1.0000
X:18177766:TAGC:T	acceptor_gain	1.0000
X:18177767:AGC:A	acceptor_gain	1.0000
X:18177768:GC:G	acceptor_gain	1.0000

AlphaMissense

5281 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:18165168:C:A	W747C	0.998
X:18165168:C:G	W747C	0.998
X:18165170:A:G	W747R	0.996
X:18165170:A:T	W747R	0.996
X:18171092:G:C	F698L	0.995
X:18171092:G:T	F698L	0.995
X:18171094:A:G	F698L	0.995
X:18165217:A:G	L731P	0.993
X:18165169:C:G	W747S	0.992
X:18165219:G:C	F730L	0.991
X:18165219:G:T	F730L	0.991
X:18165221:A:G	F730L	0.991
X:18171108:A:G	L693P	0.991
X:18171117:G:T	A690D	0.990
X:18171006:A:G	L727P	0.989
X:18176038:C:A	W562C	0.988
X:18176038:C:G	W562C	0.988
X:18171182:T:A	R668S	0.987
X:18171182:T:G	R668S	0.987
X:18176087:A:G	L546P	0.987
X:18171030:A:T	L719H	0.986
X:18171003:C:G	R728P	0.985
X:18171096:A:G	L697P	0.985
X:18171093:A:G	F698S	0.984
X:18171118:C:G	A690P	0.984
X:18171195:C:T	G664E	0.984
X:18176040:A:G	W562R	0.984
X:18176040:A:T	W562R	0.984
X:18171009:G:T	A726D	0.983
X:18171057:C:A	G710V	0.983

dbSNP variants (sampled 300 via entrez): RS1000120610 (X:18211893 T>C,G), RS1000181111 (X:18202044 C>A), RS1000184859 (X:18186949 A>G), RS1000189734 (X:18164695 T>C), RS1000247783 (X:18174744 C>T), RS1000345371 (X:18214156 G>A), RS1000457704 (X:18207508 A>G), RS1000487340 (X:18207192 C>T), RS1000522482 (X:18190197 A>G), RS1000627341 (X:18217887 C>T), RS1000643124 (X:18217239 T>C), RS1000783994 (X:18216635 T>C), RS1000844960 (X:18168330 T>C), RS1000919560 (X:18205402 A>G), RS1000963918 (X:18189236 G>C)

Disease associations

OMIM: gene MIM:301150 | disease phenotypes: MIM:300672

GenCC curated gene-disease

Mondo (1): developmental and epileptic encephalopathy, 2 (MONDO:0010396)

Orphanet (3): Early infantile developmental and epileptic encephalopathy (Orphanet:1934), West syndrome (Orphanet:3451), CDKL5-deficiency disorder (Orphanet:505652)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564064	CDKL5 deficiency disorder (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
triphenyl phosphate	affects expression	1
Air Pollutants, Occupational	increases expression	1
Arsenic	affects methylation	1
Nickel	increases expression	1

Clinical trials (associated diseases)

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