ZBED6

Summary

ZBED6 (zinc finger BED-type containing 6, HGNC:33273) is a protein-coding gene on chromosome 1q32.1, encoding Zinc finger BED domain-containing protein 6 (P86452). Transcriptional repressor which binds to the consensus sequence 5’-GCTCGC-3’, transcription regulation may be tissue-specific.

The protein encoded by this transposon-derived intronless gene is a transcriptional repressor that binds to the consensus sequence 5’-GCTCGC-3’. The encoded protein has been shown to repress IGF2 transcription. This gene is located within the first intron of the ZC3H11A gene.

Source: NCBI Gene 100381270 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 226 total
• MANE Select transcript: NM_001395895

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33273
Approved symbol	ZBED6
Name	zinc finger BED-type containing 6
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000257315
Ensembl biotype	protein_coding
OMIM	613512
Entrez	100381270

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000550078

RefSeq mRNA: 2 — MANE Select: NM_001395895 NM_001174108, NM_001395895

CCDS: CCDS55673

Canonical transcript exons

ENST00000550078 — 17 exons

Exon	Start	End
ENSE00002384654	203795623	203803016
ENSE00003802242	203833791	203833853
ENSE00003802832	203850515	203850681
ENSE00003803638	203840306	203840374
ENSE00003805095	203816926	203817124
ENSE00003805284	203837966	203838064
ENSE00003807514	203830123	203830203
ENSE00003807730	203847184	203847687
ENSE00003807838	203828299	203828422
ENSE00003807874	203829780	203829896
ENSE00003808266	203848331	203848407
ENSE00003808679	203829451	203829654
ENSE00003809003	203818570	203818689
ENSE00003809395	203849711	203850026
ENSE00003810630	203852141	203854124
ENSE00003810670	203831661	203831771
ENSE00003810860	203851057	203851124

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 87.60.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	87.60	gold quality
bone marrow cell	CL:0002092	87.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.80	gold quality
colonic epithelium	UBERON:0000397	83.90	gold quality
tonsil	UBERON:0002372	80.18	gold quality
islet of Langerhans	UBERON:0000006	79.73	gold quality
stromal cell of endometrium	CL:0002255	79.00	gold quality
calcaneal tendon	UBERON:0003701	78.92	gold quality
bone marrow	UBERON:0002371	77.36	gold quality
duodenum	UBERON:0002114	75.42	gold quality
smooth muscle tissue	UBERON:0001135	73.16	gold quality
sural nerve	UBERON:0015488	73.08	gold quality
gall bladder	UBERON:0002110	72.96	gold quality
gastrocnemius	UBERON:0001388	71.99	gold quality
lymph node	UBERON:0000029	71.44	gold quality
pancreas	UBERON:0001264	71.34	gold quality
urinary bladder	UBERON:0001255	71.24	gold quality
rectum	UBERON:0001052	71.22	gold quality
adrenal gland	UBERON:0002369	71.17	gold quality
vermiform appendix	UBERON:0001154	70.89	gold quality
placenta	UBERON:0001987	70.69	gold quality
skeletal muscle tissue	UBERON:0001134	70.45	gold quality
liver	UBERON:0002107	69.58	gold quality
body of uterus	UBERON:0009853	69.54	gold quality
muscle of leg	UBERON:0001383	69.49	gold quality
left adrenal gland	UBERON:0001234	69.48	gold quality
left adrenal gland cortex	UBERON:0035825	69.05	gold quality
muscle tissue	UBERON:0002385	69.02	gold quality
descending thoracic aorta	UBERON:0002345	68.94	gold quality
fallopian tube	UBERON:0003889	68.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.77

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
IGF2	Unknown
INS
ZC3H11A

Upstream regulators (CollecTRI, top): FOXC2

Literature-anchored findings (GeneRIF, showing 4)

• Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation. (PMID:20016685)
• Mouse MGR (Zbed6) is a repressor of Igf2. (PMID:20134481)
• results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes (PMID:26056301)
• Loss of ZBED6 Protects Against Sepsis-Induced Muscle Atrophy by Upregulating DOCK3-Mediated RAC1/PI3K/AKT Signaling Pathway in Pigs. (PMID:37551034)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zbed6	ENSMUSG00000094410
rattus_norvegicus	Zbed6	ENSRNOG00000053210
drosophila_melanogaster	CG13775	FBGN0031874
caenorhabditis_elegans		WBGENE00010704
caenorhabditis_elegans		WBGENE00015247
caenorhabditis_elegans		WBGENE00015662

Paralogs (2): ZBED4 (ENSG00000100426), ZBED1 (ENSG00000214717)

Protein

Protein identifiers

Zinc finger BED domain-containing protein 6 — P86452 (reviewed: P86452)

All UniProt accessions (1): P86452

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor which binds to the consensus sequence 5’-GCTCGC-3’, transcription regulation may be tissue-specific. Regulates the expression of target genes such as: IGF2, PGAP6/TMEM8, ENHO, and PIANP. Acts as a transcriptional repressor of growth factor IGF2, thereby negatively regulating postnatal growth of muscles and internal organs, especially in females. Negatively regulates myoblast differentiation and myoblast mitochondrial activity via its regulation of IGF2 transcription. Negatively regulates the cell cycle of myoblasts, potentially via transcriptional regulation of the E2F family of transcription factors such as: E2F1 and E2F2. Positively regulates the cell cycle and survival of pancreatic beta cells. Binds to the CDH2 gene and may directly repress CDH2 transcription. Probably by controlling CDH2 expression, regulates pancreatic beta cell adhesion, and formation of cell-to-cell junctions between pancreatic beta cells and neural crest stem cells. May also play a role in embryonic beta cell differentiation. May play a role in insulin sensitivity and glucose clearance.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Tissue specificity. Expressed in pancreatic islet cells (at protein level).

Miscellaneous. Encoded by an exapted DNA transposon located in an intron of the ZC3H11A gene.

RefSeq proteins (2): NP_001167579, NP_001382824* (*=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
IPR052865	Zinc_finger_BED	Family

Pfam: PF02892, PF05699

UniProt features (18 total): binding site 8, region of interest 4, zinc finger region 2, compositionally biased region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P86452-F1	66.98	0.25

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 (8): 154; 175; 180; 285; 288; 309; 314; 151

Post-translational modifications (1): 381

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_BLASTOCYST_DEVELOPMENT, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), blastocyst hatching (GO:0001835), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), negative regulation of muscle cell differentiation (GO:0051148), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178)

GO Molecular Function (7): transcription cis-regulatory region binding (GO:0000976), 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), protein dimerization activity (GO:0046983), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), centriolar satellite (GO:0034451)

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
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
nuclear lumen	2
negative regulation of DNA-templated transcription	1
blastocyst development	1
hatching	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
muscle cell differentiation	1
negative regulation of cell differentiation	1
regulation of muscle cell differentiation	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion	1
regulation of cellular localization	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA 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
protein binding	1
nucleic acid binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
centrosome	1

Protein interactions and networks

STRING

406 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBED6	ZC3H11A	O75152	980
ZBED6	IGF2	P01344	842
ZBED6	ZBED3	Q96IU2	545
ZBED6	ZBED5	Q49AG3	447
ZBED6	ZNF628	Q5EBL2	424
ZBED6	KIAA0408	Q6ZU52	418
ZBED6	CCDC24	Q8N4L8	380
ZBED6	ZBED2	Q9BTP6	375
ZBED6	ANKRD7	Q92527	355
ZBED6	THAP9	Q9H5L6	355
ZBED6	ZBED8	Q8IZ13	350
ZBED6	LGR5	O75473	336
ZBED6	SMIM14	Q96QK8	330
ZBED6	ZNF84	P51523	329
ZBED6	ZBTB38	Q8NAP3	329

IntAct

6 interactions, top by confidence:

A	B	Type	Score
Cep135		psi-mi:“MI:0914”(association)	0.350
Snw1	AKR7A2	psi-mi:“MI:0914”(association)	0.350
SMC6	IFT88	psi-mi:“MI:0914”(association)	0.350
Tsc1	PYGB	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): ZBED6 (Affinity Capture-MS), ZBED6 (Affinity Capture-MS), ZBED6 (Affinity Capture-MS), ZBED6 (Affinity Capture-MS), ZBED6 (Affinity Capture-RNA), ZBED6 (Affinity Capture-MS), ZBED6 (Positive Genetic), ZBED6 (Proximity Label-MS), ZBED6 (Proximity Label-MS), ZBED6 (Positive Genetic), ZBED6 (Affinity Capture-RNA), ZBED6 (Affinity Capture-MS), ZBED6 (Affinity Capture-MS), ZBED6 (Proximity Label-MS), ZBED6 (Proximity Label-MS)

ESM2 similar proteins: A3KMX0, A4IFA3, A4IGY9, A4Z943, A4Z944, B8QB46, D2EAC2, E1C2V1, O43422, O60290, P10911, P35125, P86452, Q13075, Q2NKX8, Q3UPF5, Q49AG3, Q5FWF4, Q5SVZ6, Q5T890, Q5TKR9, Q6DJS0, Q6EKJ0, Q6R2W3, Q6YI93, Q7Z2W4, Q80WE4, Q86UP8, Q86VD1, Q8BZ21, Q8N8K9, Q8QMP8, Q8TDB6, Q8WML3, Q92794, Q96JM7, Q96JS3, Q99388, Q99NI3, Q9CUX1

Diamond homologs: D2EAC2, P86452

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	179
Likely benign	18
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3006 predictions. Top by Δscore:

Variant	Effect	Δscore
1:203795749:G:GT	donor_gain	1.0000
1:203801627:GT:G	donor_gain	1.0000
1:203816921:TTTA:T	acceptor_loss	1.0000
1:203816922:TTA:T	acceptor_loss	1.0000
1:203816923:TA:T	acceptor_loss	1.0000
1:203816924:A:AG	acceptor_gain	1.0000
1:203816924:A:C	acceptor_loss	1.0000
1:203816925:G:GG	acceptor_gain	1.0000
1:203816925:G:GT	acceptor_loss	1.0000
1:203817019:G:GT	donor_gain	1.0000
1:203817084:G:GT	donor_gain	1.0000
1:203817125:G:GG	donor_gain	1.0000
1:203818566:ACAG:A	acceptor_gain	1.0000
1:203818567:CAG:C	acceptor_loss	1.0000
1:203818568:A:AG	acceptor_gain	1.0000
1:203818568:A:AT	acceptor_loss	1.0000
1:203818568:AG:A	acceptor_gain	1.0000
1:203818568:AGG:A	acceptor_gain	1.0000
1:203818568:AGGGT:A	acceptor_gain	1.0000
1:203818569:G:A	acceptor_gain	1.0000
1:203818569:G:GT	acceptor_gain	1.0000
1:203818569:GGG:G	acceptor_gain	1.0000
1:203818569:GGGT:G	acceptor_gain	1.0000
1:203818569:GGGTG:G	acceptor_gain	1.0000
1:203818685:TTGAT:T	donor_gain	1.0000
1:203818686:TGAT:T	donor_gain	1.0000
1:203818687:GAT:G	donor_gain	1.0000
1:203818687:GATG:G	donor_gain	1.0000
1:203818688:AT:A	donor_gain	1.0000
1:203818689:TGTA:T	donor_loss	1.0000

AlphaMissense

6523 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:203797920:C:T	S133F	1.000
1:203797926:T:A	V135E	1.000
1:203797928:T:A	W136R	1.000
1:203797928:T:C	W136R	1.000
1:203797930:G:C	W136C	1.000
1:203797930:G:T	W136C	1.000
1:203797937:T:C	F139L	1.000
1:203797938:T:C	F139S	1.000
1:203797939:T:A	F139L	1.000
1:203797939:T:G	F139L	1.000
1:203797965:G:C	R148P	1.000
1:203797968:C:A	A149D	1.000
1:203797973:T:A	C151S	1.000
1:203797973:T:C	C151R	1.000
1:203797974:G:A	C151Y	1.000
1:203797974:G:C	C151S	1.000
1:203797974:G:T	C151F	1.000
1:203797975:T:G	C151W	1.000
1:203797982:T:A	C154S	1.000
1:203797982:T:C	C154R	1.000
1:203797983:G:A	C154Y	1.000
1:203797983:G:C	C154S	1.000
1:203797984:T:G	C154W	1.000
1:203797995:T:A	V158D	1.000
1:203798001:G:C	R160T	1.000
1:203798001:G:T	R160M	1.000
1:203798002:G:C	R160S	1.000
1:203798002:G:T	R160S	1.000
1:203798003:G:C	G161R	1.000
1:203798003:G:T	G161C	1.000

dbSNP variants (sampled 300 via entrez): RS1000050843 (1:203840605 A>T), RS1000067608 (1:203834155 C>A,T), RS1000116443 (1:203852625 G>A), RS1000116729 (1:203818780 T>A), RS1000181035 (1:203811834 T>C), RS1000196772 (1:203805891 A>G), RS1000212804 (1:203846971 C>T), RS1000273857 (1:203852966 A>C,G), RS1000352734 (1:203846208 G>A), RS1000412682 (1:203846569 T>A,C), RS1000485729 (1:203813478 A>T), RS1000529494 (1:203810722 T>A), RS1000580159 (1:203813842 A>G), RS1000599083 (1:203807201 T>G), RS1000686170 (1:203847994 T>A)

Disease associations

OMIM: gene MIM:613512 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006661_122	Male-pattern baldness	1.000000e-15
GCST006661_4	Male-pattern baldness	8.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance, affects expression, affects cotreatment	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
geldanamycin	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenite	decreases expression	1
phenanthrene	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	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
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Rotenone	decreases expression	1
Dronabinol	increases glycosylation	1
Tobacco Smoke Pollution	affects expression	1
Urethane	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cyclosporine	increases expression	1
Okadaic Acid	decreases expression	1
Volatile Organic Compounds	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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