ZBED2

Summary

ZBED2 (zinc finger BED-type containing 2, HGNC:20710) is a protein-coding gene on chromosome 3q13.13, encoding Zinc finger BED domain-containing protein 2 (Q9BTP6). Transcriptional regulator which has intrinsic repressor activity and which competes with the transcriptional activator IRF1 for binding to the 5’-[CA]GAA[AC]C[CT]-3’ consensus sequence in gene promoters.

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of keratinocyte differentiation. Predicted to be located in chromatin.

Source: NCBI Gene 79413 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_024508

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20710
Approved symbol	ZBED2
Name	zinc finger BED-type containing 2
Location	3q13.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC10796
Ensembl gene	ENSG00000177494
Ensembl biotype	protein_coding
OMIM	615246
Entrez	79413

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000317012, ENST00000862617

RefSeq mRNA: 1 — MANE Select: NM_024508 NM_024508

CCDS: CCDS2960

Canonical transcript exons

ENST00000317012 — 2 exons

Exon	Start	End
ENSE00001236941	111592900	111595066
ENSE00001498103	111595300	111595346

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 94.55.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6572 / max 453.3914, expressed in 203 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43718	3.1348	192
43719	0.5224	121

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	94.55	gold quality
amniotic fluid	UBERON:0000173	93.68	gold quality
left lobe of thyroid gland	UBERON:0001120	91.24	gold quality
thyroid gland	UBERON:0002046	91.18	gold quality
thymus	UBERON:0002370	90.42	gold quality
right lobe of thyroid gland	UBERON:0001119	89.49	gold quality
lower esophagus mucosa	UBERON:0035834	86.50	gold quality
oral cavity	UBERON:0000167	85.56	gold quality
gingiva	UBERON:0001828	84.75	gold quality
gingival epithelium	UBERON:0001949	84.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.08	gold quality
mammalian vulva	UBERON:0000997	83.04	gold quality
right uterine tube	UBERON:0001302	82.96	gold quality
squamous epithelium	UBERON:0006914	82.48	gold quality
esophagus squamous epithelium	UBERON:0006920	82.11	gold quality
epithelium of esophagus	UBERON:0001976	81.66	gold quality
oviduct epithelium	UBERON:0004804	80.20	gold quality
cervix squamous epithelium	UBERON:0006922	79.71	silver quality
cervix epithelium	UBERON:0004801	79.24	gold quality
esophagus mucosa	UBERON:0002469	77.94	gold quality
fallopian tube	UBERON:0003889	75.43	gold quality
penis	UBERON:0000989	72.90	gold quality
body of tongue	UBERON:0011876	72.37	gold quality
tongue	UBERON:0001723	71.99	gold quality
upper lobe of left lung	UBERON:0008952	71.57	gold quality
buccal mucosa cell	CL:0002336	71.43	gold quality
upper lobe of lung	UBERON:0008948	71.11	gold quality
tonsil	UBERON:0002372	70.15	gold quality
superior surface of tongue	UBERON:0007371	70.05	gold quality
germinal epithelium of ovary	UBERON:0001304	69.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	1065.60
E-ANND-3	no	2.01

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1971.1	ZBED2	BED zinc finger factors
MA1971.2	ZBED2	BED zinc finger factors

JASPAR matrix evidence (PMIDs): PMID:32385160

miRNA regulators (miRDB)

26 targeting ZBED2, 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-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-5571-3P	97.80	66.07	640
HSA-MIR-3920	97.75	69.02	1168
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-4712-5P	97.24	67.79	775
HSA-MIR-770-5P	97.24	68.10	758
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-7976	95.75	65.67	1186

Literature-anchored findings (GeneRIF, showing 1)

• ZBED2 is an antagonist of interferon regulatory factor 1 and modifies cell identity in pancreatic cancer. (PMID:32385160)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Zinc finger BED domain-containing protein 2 — Q9BTP6 (reviewed: Q9BTP6)

All UniProt accessions (1): Q9BTP6

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator which has intrinsic repressor activity and which competes with the transcriptional activator IRF1 for binding to the 5’-[CA]GAA[AC]C[CT]-3’ consensus sequence in gene promoters. May thereby play a role in keratinocyte differentiation.

Subcellular location. Nucleus.

Tissue specificity. Expressed in keratinocytes.

Induction. Induced by TGF-beta.

RefSeq proteins (1): NP_078784* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003656	Znf_BED	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR043471	ZBED2/3	Family

Pfam: PF02892

UniProt features (18 total): strand 4, binding site 4, helix 3, region of interest 2, compositionally biased region 2, chain 1, zinc finger region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DJR	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTP6-F1	71.32	0.31

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 (4): 78; 81; 101; 106

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, FUNG_IL2_SIGNALING_2, GOBP_EPITHELIUM_DEVELOPMENT, LU_IL4_SIGNALING, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, JAEGER_METASTASIS_DN, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, ODONNELL_TARGETS_OF_MYC_AND_TFRC_UP, GOBP_POSITIVE_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_EPIDERMIS_DEVELOPMENT

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of keratinocyte differentiation (GO:0045618)

GO Molecular Function (7): 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 repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
keratinocyte differentiation	1
positive regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
positive regulation of multicellular organismal process	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
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBED2	ZBED4	O75132	560
ZBED2	ZBED10P	Q96FA7	549
ZBED2	C12orf71	A8MTZ7	417
ZBED2	ZBED1	O96006	417
ZBED2	ZBED5	Q49AG3	393
ZBED2	ZBED6	P86452	375
ZBED2	ENPP5	Q9UJA9	336
ZBED2	PKHD1L1	Q86WI1	328
ZBED2	PROSER2	Q86WR7	323
ZBED2	SLC26A7	Q8TE54	315
ZBED2	KLHL14	Q9P2G3	313
ZBED2	RBM47	A0AV96	312
ZBED2	DUOXA1	Q1HG43	307
ZBED2	KCNAB1	Q14722	302
ZBED2	MUC15	Q8N387	300

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ZBED2	POT1	psi-mi:“MI:0915”(physical association)	0.370
ZBED2	NXF1	psi-mi:“MI:0915”(physical association)	0.370
ZBED2	CFTR	psi-mi:“MI:0915”(physical association)	0.370
PLOD1	PLOD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): ZBED2 (Affinity Capture-RNA), ZBED2 (Affinity Capture-MS), ZBED2 (PCA), ZBED2 (Two-hybrid), ZBED2 (Two-hybrid)

ESM2 similar proteins: A0A1W2PP81, A0A1W2PPE2, A0A1W2PPH5, A0A1W2PPL8, A0A1W2PR64, A0A1W2PRV1, A0A3B3IU63, A4QVR2, A5DQL2, A9UMV8, F4HR03, O35216, P06898, P0C1H6, P0C5Y9, P0C5Z0, P0DW11, P0DW12, P0DW13, P0DW14, P0DW85, P35061, P48003, P49450, Q00728, Q3SZB8, Q3ZBX9, Q4IMD1, Q5M8Q2, Q5TKR9, Q64522, Q64598, Q7Z2G1, Q803H4, Q873G4, Q8BRB7, Q8BZ21, Q8CGP5, Q8IUE6, Q8R1M2

Diamond homologs: Q96IU2, Q9BTP6, Q9D0L1, O75132

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	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

87 predictions. Top by Δscore:

Variant	Effect	Δscore
3:111595298:A:AC	donor_gain	1.0000
3:111595299:C:CC	donor_gain	1.0000
3:111595299:CAA:C	donor_gain	1.0000
3:111595299:CAAG:C	donor_gain	1.0000
3:111595294:ACTT:A	donor_loss	0.9900
3:111595296:TTACA:T	donor_loss	0.9900
3:111595297:TA:T	donor_loss	0.9900
3:111595298:AC:A	donor_loss	0.9900
3:111595298:ACAAG:A	donor_gain	0.9900
3:111595299:CA:C	donor_gain	0.9900
3:111595299:CAAGC:C	donor_gain	0.9900
3:111595292:GTACT:G	donor_loss	0.9800
3:111595293:TACTT:T	donor_loss	0.9800
3:111595291:GGTAC:G	donor_loss	0.9300
3:111595334:T:A	donor_gain	0.9200
3:111595294:A:AC	donor_gain	0.7700
3:111595295:C:CC	donor_gain	0.7700
3:111595064:CACCT:C	acceptor_loss	0.7600
3:111595065:ACC:A	acceptor_loss	0.7600
3:111595066:CCT:C	acceptor_loss	0.7600
3:111595067:CTGC:C	acceptor_loss	0.7600
3:111595068:T:A	acceptor_loss	0.7600
3:111595069:G:C	acceptor_loss	0.7300
3:111595132:T:TG	acceptor_gain	0.7100
3:111595314:C:CA	acceptor_gain	0.7100
3:111595315:TG:T	acceptor_gain	0.6800
3:111595316:GG:G	acceptor_gain	0.6800
3:111595063:TCAC:T	acceptor_gain	0.6500
3:111595064:CAC:C	acceptor_gain	0.6500
3:111595064:CACC:C	acceptor_gain	0.6500

AlphaMissense

1446 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:111594019:G:C	F61L	0.998
3:111594019:G:T	F61L	0.998
3:111594021:A:G	F61L	0.998
3:111593899:A:C	H101Q	0.996
3:111593899:A:T	H101Q	0.996
3:111594020:A:G	F61S	0.995
3:111594028:C:A	W58C	0.995
3:111594028:C:G	W58C	0.995
3:111594030:A:G	W58R	0.995
3:111594030:A:T	W58R	0.995
3:111593897:A:G	L102P	0.992
3:111593901:G:C	H101D	0.992
3:111593970:A:G	C78R	0.992
3:111593975:G:T	A76D	0.992
3:111593940:C:G	G88R	0.991
3:111593900:T:C	H101R	0.990
3:111593901:G:T	H101N	0.989
3:111593905:C:A	W99C	0.988
3:111593905:C:G	W99C	0.988
3:111593907:A:G	W99R	0.988
3:111593907:A:T	W99R	0.988
3:111593909:A:T	L98Q	0.988
3:111594020:A:C	F61C	0.988
3:111593884:G:C	H106Q	0.987
3:111593884:G:T	H106Q	0.987
3:111593944:G:C	S86R	0.987
3:111593944:G:T	S86R	0.987
3:111593946:T:G	S86R	0.987
3:111593961:A:G	C81R	0.987
3:111593968:G:C	C78W	0.987

dbSNP variants (sampled 300 via entrez): RS1000296844 (3:111594516 G>A,T), RS1000910085 (3:111595207 G>A), RS1002851713 (3:111592873 T>C), RS1003314654 (3:111592605 A>G), RS1003629569 (3:111597184 T>C), RS1004356838 (3:111592470 C>A,T), RS1004917009 (3:111596830 C>A), RS1006198590 (3:111595618 T>A,G), RS1006825348 (3:111593439 C>A), RS1008168540 (3:111594831 T>C), RS1008376559 (3:111596512 C>A), RS1008453412 (3:111593937 G>A), RS1009038611 (3:111596834 A>T), RS1009633399 (3:111594791 A>G), RS1010388414 (3:111593499 A>G)

Disease associations

OMIM: gene MIM:615246 | 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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, decreases methylation	4
Estradiol	affects cotreatment, increases expression, decreases expression	3
Progesterone	affects cotreatment, decreases expression, increases expression	3
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
terbufos	increases methylation	1
butyraldehyde	increases expression	1
hydroquinone	increases expression	1
triacsin C	decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
monomethylarsonous acid	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Aldehydes	increases expression	1
Amphotericin B	decreases expression	1
Vehicle Emissions	decreases methylation	1
Benzo(a)pyrene	decreases methylation	1
Diethylnitrosamine	increases expression	1
Fonofos	increases methylation	1
Formaldehyde	increases expression	1
Parathion	increases methylation	1
Phenobarbital	decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases methylation	1

Clinical trials (associated diseases)

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