ZBED4

Summary

ZBED4 (zinc finger BED-type containing 4, HGNC:20721) is a protein-coding gene on chromosome 22q13.33, encoding Zinc finger BED domain-containing protein 4 (O75132). Transcriptional regulator that binds to poly-guanine tracts in gene promoters and activates transcription.

Enables identical protein binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleoplasm.

Source: NCBI Gene 9889 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 2 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_014838

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20721
Approved symbol	ZBED4
Name	zinc finger BED-type containing 4
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0637
Ensembl gene	ENSG00000100426
Ensembl biotype	protein_coding
OMIM	612552
Entrez	9889

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000216268, ENST00000850559, ENST00000850560, ENST00000891849, ENST00000921492, ENST00000921493, ENST00000921494, ENST00000942855

RefSeq mRNA: 1 — MANE Select: NM_014838 NM_014838

CCDS: CCDS33677

Canonical transcript exons

ENST00000216268 — 2 exons

Exon	Start	End
ENSE00000657465	49883334	49890080
ENSE00001032543	49853844	49853989

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 86.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7525 / max 73.3363, expressed in 1715 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192928	3.9185	1585
192929	1.7974	1060
192927	0.0366	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	86.57	gold quality
cortical plate	UBERON:0005343	86.46	gold quality
embryo	UBERON:0000922	83.33	gold quality
ventricular zone	UBERON:0003053	83.28	gold quality
secondary oocyte	CL:0000655	81.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.92	gold quality
monocyte	CL:0000576	79.26	gold quality
mononuclear cell	CL:0000842	79.17	gold quality
leukocyte	CL:0000738	79.15	gold quality
stromal cell of endometrium	CL:0002255	79.02	gold quality
mucosa of transverse colon	UBERON:0004991	77.11	gold quality
lower esophagus mucosa	UBERON:0035834	76.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.69	gold quality
esophagus mucosa	UBERON:0002469	75.44	gold quality
gastrocnemius	UBERON:0001388	75.34	gold quality
granulocyte	CL:0000094	74.94	gold quality
islet of Langerhans	UBERON:0000006	74.92	gold quality
muscle of leg	UBERON:0001383	74.87	gold quality
rectum	UBERON:0001052	74.64	gold quality
transverse colon	UBERON:0001157	73.77	gold quality
oocyte	CL:0000023	73.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.45	gold quality
cerebellar hemisphere	UBERON:0002245	73.34	gold quality
cerebellar cortex	UBERON:0002129	73.32	gold quality
esophagus	UBERON:0001043	73.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.21	gold quality
pancreas	UBERON:0001264	72.56	gold quality
bone marrow cell	CL:0002092	72.52	silver quality
cerebellum	UBERON:0002037	72.44	gold quality
body of pancreas	UBERON:0001150	72.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.43

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2328.1	ZBED4	BED zinc finger factors

JASPAR matrix evidence (PMIDs): PMID:22693546

miRNA regulators (miRDB)

93 targeting ZBED4, 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-3662	99.99	73.82	5684
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700

Literature-anchored findings (GeneRIF, showing 3)

• ZBED4 cellular/subcellular localization and domains suggest a regulatory role for this protein, which may exert its effects in cones and Muller cells through multiple ways of action. (PMID:19369242)
• ZBED4, a novel protein that in human retina is localized to cone photoreceptors and glial Muller cells. (PMID:20238005)
• There was no association between SNPs in the BRD1 and ZBED4 genes and schizophrenia in the Chinese population. (PMID:29794561)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbed4	ENSDARG00000024306
mus_musculus	Zbed4	ENSMUSG00000034333
rattus_norvegicus	Zbed4	ENSRNOG00000004588

Paralogs (2): ZBED1 (ENSG00000214717), ZBED6 (ENSG00000257315)

Protein

Protein identifiers

Zinc finger BED domain-containing protein 4 — O75132 (reviewed: O75132)

All UniProt accessions (1): O75132

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator that binds to poly-guanine tracts in gene promoters and activates transcription. Able to bind single- and double-stranded DNA and RNA.

Subunit / interactions. Homodimer; via C-terminus. Interacts with MYH9. Interacts with SAFB/SAFB1.

Subcellular location. Nucleus. Cytoplasm. Photoreceptor inner segment.

Tissue specificity. Expressed in testis, heart, lung, and weakly expressed in brain, liver, muscle, placenta and small intestine. Expressed in the retina, found in the cone photoreceptors, Mueller cells, cone pedicles and in the innermost retinal layer.

RefSeq proteins (1): NP_055653* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003656	Znf_BED	Domain
IPR008906	HATC_C_dom	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR052035	ZnF_BED_domain_contain	Family

Pfam: PF02892, PF05699

UniProt features (32 total): binding site 16, zinc finger region 4, region of interest 4, compositionally biased region 2, cross-link 2, chain 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75132-F1	67.86	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (16): 136; 139; 160; 165; 306; 309; 330; 335; 477; 480; 500; 505 …

Post-translational modifications (3): 624, 43, 489

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, MODULE_45, AAGCCAT_MIR135A_MIR135B, MODULE_16, NIKOLSKY_BREAST_CANCER_22Q13_AMPLICON, GTGCCTT_MIR506, MODULE_118, MODULE_205, AAACCAC_MIR140, GENTILE_UV_RESPONSE_CLUSTER_D2, GENTILE_UV_HIGH_DOSE_DN, MODULE_88, DOUGLAS_BMI1_TARGETS_UP, TGCCTTA_MIR124A, HEIDENBLAD_AMPLICON_12P11_12_DN

GO Biological Process (1): positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (11): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), RNA binding (GO:0003723), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein dimerization activity (GO:0046983), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), photoreceptor inner segment (GO:0001917), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
nucleic acid binding	2
protein binding	2
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
transcription cis-regulatory region binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBED4	ZBED10P	Q96FA7	567
ZBED4	ZBED2	Q9BTP6	560
ZBED4	BRD1	O95696	469
ZBED4	TBC1D22A	Q8WUA7	419
ZBED4	ZBED3	Q96IU2	418
ZBED4	CBY2	Q8NA61	414
ZBED4	SCAND3	Q6R2W3	402
ZBED4	TMPRSS11D	O60235	395
ZBED4	AMMECR1	Q9Y4X0	389
ZBED4	PDZRN4	Q6ZMN7	382
ZBED4	ZBED5	Q49AG3	373
ZBED4	C2orf49	Q9BVC5	373
ZBED4	FAHD2B	Q6P2I3	370
ZBED4	ZBED8	Q8IZ13	366
ZBED4	EEF1AKMT1	Q8WVE0	366

IntAct

30 interactions, top by confidence:

A	B	Type	Score
ZBED4	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	ZBED4	psi-mi:“MI:0915”(physical association)	0.560
CBX1	KPNA3	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZBED4	DHX9	psi-mi:“MI:0915”(physical association)	0.400
ZBED4	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
MLF1	ZBED4	psi-mi:“MI:0915”(physical association)	0.400
Hacd3	ZBED4	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	ZBED4	psi-mi:“MI:0915”(physical association)	0.400
NUDCD3	ZBED4	psi-mi:“MI:0915”(physical association)	0.400
HSP90AA1	ZBED4	psi-mi:“MI:0915”(physical association)	0.400
ZBED4	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
ZBED4	ZBED4	psi-mi:“MI:0915”(physical association)	0.370
ZBED4		psi-mi:“MI:0915”(physical association)	0.370
NOTCH1	CNOT1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
ABT1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
FAXC	METTL15	psi-mi:“MI:0914”(association)	0.350
PTX3	POLRMT	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
E2F3	MYO1C	psi-mi:“MI:0914”(association)	0.350
DISC1	ZBED4	psi-mi:“MI:0915”(physical association)	0.000
rlmN	ZBED4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): ZBED4 (Two-hybrid), ZBED4 (Two-hybrid), ZBED4 (Affinity Capture-RNA), ZBED4 (Affinity Capture-MS), ZBED4 (Affinity Capture-RNA), ZBED4 (Affinity Capture-MS), DHX9 (Proximity Label-MS), ZBED4 (Positive Genetic), ZBED4 (Affinity Capture-MS), ZBED4 (Affinity Capture-MS), ZBED4 (Proximity Label-MS), ZBED4 (Affinity Capture-MS), ZBED4 (Affinity Capture-MS), ZBED4 (Affinity Capture-MS), ZBED4 (Affinity Capture-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: O75132, Q0JMB2, Q80WQ9, Q19787, Q96IU2, Q9BTP6, Q9D0L1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1328447	GRCh37/hg19 22q13.31-13.33(chr22:47554026-51186813)x1	Pathogenic

SpliceAI

662 predictions. Top by Δscore:

Variant	Effect	Δscore
22:49853988:AGG:A	donor_loss	1.0000
22:49853990:G:GA	donor_loss	1.0000
22:49853991:T:G	donor_loss	1.0000
22:49880667:G:GG	donor_gain	1.0000
22:49853987:GAG:G	donor_gain	0.9900
22:49853990:G:GG	donor_gain	0.9900
22:49854810:G:GT	donor_gain	0.9900
22:49876702:A:G	donor_gain	0.9900
22:49880563:GC:G	acceptor_gain	0.9900
22:49880663:GACT:G	donor_gain	0.9900
22:49854810:G:T	donor_gain	0.9800
22:49854418:G:GT	donor_gain	0.9700
22:49880658:G:GT	donor_gain	0.9700
22:49874482:TTC:T	donor_gain	0.9600
22:49880677:C:G	donor_gain	0.9600
22:49853988:AG:A	donor_gain	0.9500
22:49853989:GG:G	donor_gain	0.9500
22:49880562:A:AG	acceptor_gain	0.9500
22:49880563:G:GG	acceptor_gain	0.9500
22:49883328:TTATA:T	acceptor_loss	0.9500
22:49883329:TATA:T	acceptor_loss	0.9500
22:49883331:TAGGT:T	acceptor_loss	0.9500
22:49883332:A:T	acceptor_loss	0.9500
22:49883333:G:GA	acceptor_loss	0.9500
22:49880664:ACTG:A	donor_loss	0.9300
22:49880665:CTG:C	donor_loss	0.9300
22:49880666:TGT:T	donor_loss	0.9300
22:49880667:G:GT	donor_loss	0.9300
22:49880668:T:G	donor_loss	0.9300
22:49880669:G:GC	donor_loss	0.9300

AlphaMissense

7754 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:49884068:T:C	C136R	1.000
22:49884070:C:G	C136W	1.000
22:49884578:T:C	C306R	1.000
22:49884580:C:G	C306W	1.000
22:49885352:T:A	W564R	1.000
22:49885352:T:C	W564R	1.000
22:49885397:T:C	C579R	1.000
22:49885428:G:A	G589E	1.000
22:49885471:T:A	H603Q	1.000
22:49885471:T:G	H603Q	1.000
22:49884023:T:A	W121R	0.999
22:49884023:T:C	W121R	0.999
22:49884025:G:C	W121C	0.999
22:49884025:G:T	W121C	0.999
22:49884032:T:C	F124L	0.999
22:49884033:T:C	F124S	0.999
22:49884034:T:A	F124L	0.999
22:49884034:T:G	F124L	0.999
22:49884068:T:A	C136S	0.999
22:49884069:G:A	C136Y	0.999
22:49884069:G:C	C136S	0.999
22:49884089:T:C	F143L	0.999
22:49884090:T:C	F143S	0.999
22:49884091:C:A	F143L	0.999
22:49884091:C:G	F143L	0.999
22:49884119:A:C	S153R	0.999
22:49884121:T:A	S153R	0.999
22:49884121:T:G	S153R	0.999
22:49884132:T:C	L157P	0.999
22:49884533:T:A	W291R	0.999

dbSNP variants (sampled 300 via entrez): RS1000111270 (22:49861578 C>T), RS1000129127 (22:49872619 T>A), RS1000149486 (22:49879006 G>T), RS1000163812 (22:49861390 C>T), RS1000171927 (22:49858402 G>A), RS1000333191 (22:49863338 T>G), RS1000452059 (22:49851603 ATG>A), RS1000502121 (22:49862327 T>G), RS1000605752 (22:49859233 T>A,C), RS1000652841 (22:49857331 G>C), RS1000724015 (22:49856255 G>A,C,T), RS1000747364 (22:49864864 T>A), RS1000774008 (22:49853117 C>A,T), RS1000812167 (22:49863550 C>T), RS1000957645 (22:49888929 G>C)

Disease associations

OMIM: gene MIM:612552 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002481_12	Acne (severe)	4.000000e-06
GCST006979_836	Heel bone mineral density	8.000000e-15
GCST009391_1050	Metabolite levels	3.000000e-06
GCST90002395_626	Mean platelet volume	9.000000e-25

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0010358	lysophosphatidylcholine 16:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725051 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases mutagenesis	3
sodium arsenite	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	increases methylation, increases expression	2
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697602	Binding	Inhibition of ZBED4 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7Z6	SEES3-1V human ZBED4, clone1	Embryonic stem cell	Male
CVCL_A7Z7	SEES3-1V human ZBED4, clone2	Embryonic stem cell	Male
CVCL_A7Z8	SEES3-1V human ZBED4, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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