BEND4

Summary

BEND4 (BEN domain containing 4, HGNC:23815) is a protein-coding gene on chromosome 4p13, encoding BEN domain-containing protein 4 (Q6ZU67).

Predicted to enable DNA binding activity.

Source: NCBI Gene 389206 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_207406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23815
Approved symbol	BEND4
Name	BEN domain containing 4
Location	4p13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35632, FLJ43965
Ensembl gene	ENSG00000188848
Ensembl biotype	protein_coding
OMIM	621197
Entrez	389206

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000502486, ENST00000504360

RefSeq mRNA: 2 — MANE Select: NM_207406 NM_001159547, NM_207406

CCDS: CCDS47048

Canonical transcript exons

ENST00000502486 — 6 exons

Exon	Start	End
ENSE00001366131	42151657	42152376
ENSE00001381242	42120054	42120294
ENSE00001384924	42143428	42143994
ENSE00001386236	42125583	42125674
ENSE00002070216	42110853	42117735
ENSE00003848772	42152532	42152655

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 91.97.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7017 / max 86.0602, expressed in 363 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51961	0.7330	253
51962	0.3049	134
51960	0.2182	112
203159	0.1641	99
51964	0.1587	75
51959	0.0835	47
51958	0.0291	6
51963	0.0102	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.81	gold quality
ventricular zone	UBERON:0003053	79.73	gold quality
ganglionic eminence	UBERON:0004023	75.83	gold quality
adult organism	UBERON:0007023	73.68	gold quality
testis	UBERON:0000473	70.48	gold quality
substantia nigra pars reticulata	UBERON:0001966	69.20	gold quality
ileal mucosa	UBERON:0000331	68.72	gold quality
right testis	UBERON:0004534	67.59	gold quality
substantia nigra pars compacta	UBERON:0001965	66.17	silver quality
left testis	UBERON:0004533	65.80	gold quality
lymph node	UBERON:0000029	64.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	64.60	silver quality
middle temporal gyrus	UBERON:0002771	63.98	silver quality
cortical plate	UBERON:0005343	63.02	gold quality
endothelial cell	CL:0000115	62.66	silver quality
vermiform appendix	UBERON:0001154	62.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	60.96	silver quality
prefrontal cortex	UBERON:0000451	59.22	gold quality
prostate gland	UBERON:0002367	58.59	gold quality
spleen	UBERON:0002106	58.41	gold quality
bone marrow cell	CL:0002092	57.76	gold quality
caecum	UBERON:0001153	57.60	gold quality
substantia nigra	UBERON:0002038	56.88	gold quality
superior frontal gyrus	UBERON:0002661	56.13	gold quality
entorhinal cortex	UBERON:0002728	55.81	silver quality
midbrain	UBERON:0001891	55.15	gold quality
colonic epithelium	UBERON:0000397	55.13	gold quality
neocortex	UBERON:0001950	55.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	55.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

350 targeting BEND4, 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-3613-3P	100.00	76.36	7965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4803	99.98	71.99	3117

Literature-anchored findings (GeneRIF, showing 2)

• BEND4 hypermethylation is associated with lung cancer. (PMID:28722770)
• Genetic Variants May Play Role in Opioid Dependence. (PMID:32453508)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	BEND4	ENSDARG00000113607
mus_musculus	Bend4	ENSMUSG00000092060
rattus_norvegicus	Bend4	ENSRNOG00000053303

Protein

Protein identifiers

BEN domain-containing protein 4 — Q6ZU67 (reviewed: Q6ZU67)

Alternative names: Coiled-coil domain-containing protein 4

All UniProt accessions (2): A0A0C4DGA9, Q6ZU67

UniProt curated annotations — full annotation on UniProt →

Isoforms (5)

UniProt ID	Names	Canonical?
Q6ZU67-1	1	yes
Q6ZU67-2	2
Q6ZU67-3	3
Q6ZU67-4	4
Q6ZU67-5	5

RefSeq proteins (2): NP_001153019, NP_997289* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018379	BEN_domain	Domain
IPR038950	BEND4	Family

Pfam: PF10523

UniProt features (18 total): splice variant 7, compositionally biased region 5, region of interest 3, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZU67-F1	60.57	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 210 (showing top): GAANYNYGACNY_UNKNOWN, USF_C, CAGCTG_AP4_Q5, PAX2_01, PAX8_B, CEBP_Q2, NKX62_Q2, MYCMAX_01, OCT1_03, WTGAAAT_UNKNOWN, TCF11_01, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, OCT1_06, MYB_Q3, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (0):

GO Molecular Function (1): DNA binding (GO:0003677)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1

Protein interactions and networks

STRING

538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BEND4	SLC30A9	Q6PML9	628
BEND4	BEND2	Q8NDZ0	530
BEND4	ZNF583	Q96ND8	484
BEND4	TMEM33	P57088	482
BEND4	LRRC66	Q68CR7	457
BEND4	SHISA3	A0PJX4	448
BEND4	OR6S1	Q8NH40	445
BEND4	CNIH3	Q8TBE1	432
BEND4	PDCL2	Q8N4E4	424
BEND4	ELP6	Q0PNE2	415
BEND4	ZCCHC7	Q8N3Z6	414
BEND4	KCNG2	Q9UJ96	410
BEND4	RSU1	Q15404	404
BEND4	TMEM156	Q8N614	374
BEND4	SFMBT2	Q5VUG0	373

IntAct

3 interactions, top by confidence:

A	B	Type	Score
JUN	NKRF	psi-mi:“MI:0914”(association)	0.460
M1	TUBB	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): BEND4 (Affinity Capture-MS), BEND4 (Affinity Capture-MS), BEND4 (Proximity Label-MS), BEND4 (Proximity Label-MS), BEND4 (Proximity Label-MS)

ESM2 similar proteins: A0JNG6, A2AKB4, A7YWL5, B0BN13, O35181, O43734, O70142, O70240, O88286, O88566, P0DPB3, P0DPB4, P56975, P70298, P86174, P97303, Q00IB7, Q1LY51, Q2M3C6, Q2T9L4, Q3TY60, Q498S6, Q4V7B1, Q568Z1, Q5HZN9, Q5JTD0, Q5SYB0, Q5U5E5, Q5VT97, Q69ZB8, Q6PG95, Q6UXB0, Q6ZU67, Q76N89, Q80YE4, Q86XD5, Q8BWU3, Q8BZB3, Q8CD60, Q8N365

Diamond homologs: P86174, Q6ZU67

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1034 predictions. Top by Δscore:

Variant	Effect	Δscore
4:42117561:T:TA	donor_gain	1.0000
4:42120157:AAG:A	donor_gain	1.0000
4:42120157:AAGCT:A	donor_gain	1.0000
4:42125578:CCTA:C	donor_loss	1.0000
4:42125579:CTA:C	donor_loss	1.0000
4:42125580:TACCT:T	donor_loss	1.0000
4:42125582:C:A	donor_loss	1.0000
4:42125582:CCT:C	donor_gain	1.0000
4:42125670:GGGCA:G	acceptor_gain	1.0000
4:42125671:GGCA:G	acceptor_gain	1.0000
4:42125672:GCA:G	acceptor_gain	1.0000
4:42125672:GCAC:G	acceptor_loss	1.0000
4:42125673:CA:C	acceptor_gain	1.0000
4:42125673:CAC:C	acceptor_gain	1.0000
4:42125675:C:CC	acceptor_gain	1.0000
4:42125679:G:C	acceptor_gain	1.0000
4:42143991:CTCT:C	acceptor_gain	1.0000
4:42143993:CT:C	acceptor_gain	1.0000
4:42117534:T:TA	donor_gain	0.9900
4:42117558:T:TA	donor_gain	0.9900
4:42120157:A:AC	donor_gain	0.9900
4:42120158:A:C	donor_gain	0.9900
4:42120181:T:C	donor_gain	0.9900
4:42125563:CCTTT:C	donor_gain	0.9900
4:42125579:CT:C	donor_gain	0.9900
4:42125580:TA:T	donor_gain	0.9900
4:42125581:A:AC	donor_gain	0.9900
4:42125582:C:CC	donor_gain	0.9900
4:42125672:GCACT:G	acceptor_gain	0.9900
4:42125674:ACT:A	acceptor_gain	0.9900

AlphaMissense

3464 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:42117634:C:G	G497R	1.000
4:42117634:C:T	G497R	1.000
4:42117639:C:G	R495P	1.000
4:42117642:G:T	A494D	1.000
4:42117646:G:C	H493D	1.000
4:42117648:C:A	G492V	1.000
4:42117648:C:T	G492D	1.000
4:42117649:C:A	G492C	1.000
4:42117649:C:G	G492R	1.000
4:42117651:A:T	V491D	1.000
4:42117654:G:T	A490D	1.000
4:42117655:C:G	A490P	1.000
4:42117657:T:A	D489V	1.000
4:42117657:T:C	D489G	1.000
4:42117657:T:G	D489A	1.000
4:42117658:C:A	D489Y	1.000
4:42117658:C:G	D489H	1.000
4:42117659:G:C	S488R	1.000
4:42117659:G:T	S488R	1.000
4:42117660:C:A	S488I	1.000
4:42117661:T:G	S488R	1.000
4:42117662:G:C	F487L	1.000
4:42117662:G:T	F487L	1.000
4:42117663:A:C	F487C	1.000
4:42117663:A:G	F487S	1.000
4:42117664:A:G	F487L	1.000
4:42117666:A:T	V486E	1.000
4:42117668:T:A	K485N	1.000
4:42117668:T:G	K485N	1.000
4:42117669:T:A	K485I	1.000

dbSNP variants (sampled 300 via entrez): RS1000091765 (4:42129654 T>A,G), RS1000234016 (4:42118162 T>C), RS1000290012 (4:42149863 G>A,T), RS1000382220 (4:42120991 C>A,G,T), RS1000384129 (4:42134824 G>T), RS1000396899 (4:42112565 A>G), RS1000409705 (4:42127147 T>C), RS1000520266 (4:42144520 A>G), RS1000592183 (4:42134644 G>C,T), RS1000619087 (4:42134272 C>T), RS1000657463 (4:42133198 T>C), RS1000669986 (4:42122288 A>C), RS1000746306 (4:42128348 G>A), RS1000789694 (4:42128317 A>G), RS1000816991 (4:42128162 AAAAC>A,AAAACAAAC)

Disease associations

OMIM: gene MIM:621197 | disease phenotypes: MIM:608033

GenCC curated gene-disease

Mondo (1): familial acute necrotizing encephalopathy (MONDO:0011953)

Orphanet (1): Familial acute necrotizing encephalopathy (Orphanet:88619)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003425_6	Longevity	3.000000e-07
GCST005355_3	Helping behaviour (self reported)	5.000000e-07
GCST005355_5	Helping behaviour (self reported)	3.000000e-06
GCST007627_5	Impulsivity (attentional)	4.000000e-06
GCST008757_23	Alcohol consumption	3.000000e-11
GCST008811_16	Alcohol consumption (drinks per week)	1.000000e-09
GCST009852_1	Opioid exposure	7.000000e-08
GCST010002_5	Refractive error	4.000000e-09
GCST010456_1	Anthracycline-induced cardiotoxicity in early breast cancer	4.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006946	behavioural disinhibition measurement
EFO:0009937	Opioid use measurement
EFO:0005257	response to anthracycline-based chemotherapy
EFO:1001482	cardiotoxicity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	5
trichostatin A	increases expression, affects cotreatment, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Fulvestrant	increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Dihydrotestosterone	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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