ZBTB49

Summary

ZBTB49 (zinc finger and BTB domain containing 49, HGNC:19883) is a protein-coding gene on chromosome 4p16.3, encoding Zinc finger and BTB domain-containing protein 49 (Q6ZSB9). Transcription factor.

Enables DNA-binding transcription factor binding activity; sequence-specific DNA binding activity; and transcription coactivator binding activity. Involved in negative regulation of cell population proliferation; positive regulation of transcription by RNA polymerase II; and regulation of cell cycle. Located in cytosol; microtubule cytoskeleton; and nucleoplasm.

Source: NCBI Gene 166793 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_145291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19883
Approved symbol	ZBTB49
Name	zinc finger and BTB domain containing 49
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38559
Ensembl gene	ENSG00000168826
Ensembl biotype	protein_coding
OMIM	616238
Entrez	166793

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 nonsense_mediated_decay

ENST00000337872, ENST00000502918, ENST00000503703, ENST00000504302, ENST00000511458, ENST00000515012, ENST00000880133, ENST00000880134, ENST00000924925, ENST00000942737

RefSeq mRNA: 2 — MANE Select: NM_145291 NM_001330625, NM_145291

CCDS: CCDS3375

Canonical transcript exons

ENST00000337872 — 8 exons

Exon	Start	End
ENSE00001161956	4306138	4306184
ENSE00001816271	4290251	4290352
ENSE00003473135	4301989	4303091
ENSE00003526559	4313041	4313114
ENSE00003529657	4320640	4321783
ENSE00003556023	4315809	4315970
ENSE00003558276	4315636	4315718
ENSE00003630125	4299927	4300097

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 94.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8863 / max 74.3740, expressed in 1669 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46731	4.8863	1669

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.91	gold quality
secondary oocyte	CL:0000655	93.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.31	gold quality
ventricular zone	UBERON:0003053	80.28	gold quality
granulocyte	CL:0000094	80.09	gold quality
tibialis anterior	UBERON:0001385	78.77	silver quality
cortical plate	UBERON:0005343	78.67	gold quality
pituitary gland	UBERON:0000007	77.76	gold quality
ganglionic eminence	UBERON:0004023	76.96	gold quality
adenohypophysis	UBERON:0002196	76.66	gold quality
gastrocnemius	UBERON:0001388	75.82	gold quality
muscle of leg	UBERON:0001383	75.53	gold quality
right ovary	UBERON:0002118	75.21	gold quality
blood	UBERON:0000178	74.96	gold quality
popliteal artery	UBERON:0002250	74.77	gold quality
tibial artery	UBERON:0007610	74.77	gold quality
leukocyte	CL:0000738	74.73	gold quality
monocyte	CL:0000576	74.42	gold quality
tendon of biceps brachii	UBERON:0008188	74.25	gold quality
smooth muscle tissue	UBERON:0001135	74.20	gold quality
calcaneal tendon	UBERON:0003701	74.09	gold quality
tendon	UBERON:0000043	74.00	gold quality
stromal cell of endometrium	CL:0002255	73.93	gold quality
spleen	UBERON:0002106	73.83	gold quality
left ovary	UBERON:0002119	73.69	gold quality
vermiform appendix	UBERON:0001154	73.58	gold quality
aorta	UBERON:0000947	73.44	gold quality
ectocervix	UBERON:0012249	73.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	73.13	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	151.05
E-MTAB-6379	no	173.15
E-ANND-3	no	2.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting ZBTB49, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-4794	96.47	65.53	1063
HSA-MIR-6760-3P	96.35	68.31	1001
HSA-MIR-664A-5P	95.84	64.93	949

Literature-anchored findings (GeneRIF, showing 2)

• Two major ZNF509 isoforms are induced by p53 and act as downstream executioners of cell-cycle arrest by inducing expression of p21 and RB. (PMID:25245946)
• ZNF509S1 modulation of p53 activity. (PMID:28757384)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb49	ENSDARG00000102111
mus_musculus	Zbtb49	ENSMUSG00000029127
rattus_norvegicus	Zbtb49	ENSRNOG00000005633

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 49 — Q6ZSB9 (reviewed: Q6ZSB9)

Alternative names: Zinc finger protein 509

All UniProt accessions (6): Q6ZSB9, D6RB16, D6RC96, D6RJ00, H0Y8P2, H0YAD4

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. Inhibits cell proliferation by activating either CDKN1A/p21 transcription or RB1 transcription. Binds CDKN1A promoter and activates its transcription; this activity is further potentiated in the presence of EP300 (synergistic) and ZBTB17/Miz-1 (additive). Activates RB1 transcription most probably by antagonizing ZBTB17 repression of RB1. Does not bind directly RB1 promoter.

Subunit / interactions. Isoform 1 interacts with EP300 and KAT5/Tip60. The interaction with EP300 is direct and leads to synergistic induction of CDKN1A. On the CDKN1A promoter, forms a complex with ZBTB17/Miz-1; this interaction leads to additive CDKN1A transactivation. Isoform 3 also interacts with ZBTB17; this interaction may block ZBTB17 repressor activity.

Subcellular location. Cytoplasm. Nucleus Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in normal epidermis and in other epithelial tissues, including in colon and lung. Tends to be down-regulated in colon, lung and skin cancer tissues.

Induction. Induced by the DNA-damaging agent etoposide. This induction is mediated by TP53 at the transcriptional level.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6ZSB9-1	1, ZNF509L	yes
Q6ZSB9-2	2
Q6ZSB9-3	3, ZNF509S1
Q6ZSB9-4	4, ZNF509S2
Q6ZSB9-5	5, ZNF509S3

RefSeq proteins (2): NP_001317554, NP_660334* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050457	ZnFinger_BTB_dom_contain	Family

Pfam: PF00096, PF00651, PF13912

UniProt features (24 total): zinc finger region 7, splice variant 6, sequence variant 4, sequence conflict 3, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZSB9-F1	57.70	0.01

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): CMYB_01, USF_C, MYCMAX_01, GOBP_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_CELL_CYCLE, chr4p16, GOMF_TRANSCRIPTION_COREGULATOR_BINDING, GOMF_TRANSCRIPTION_COACTIVATOR_BINDING, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_BINDING

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cytokine production (GO:0001817), regulation of immune system process (GO:0002682), negative regulation of cell population proliferation (GO:0008285), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of cell cycle (GO:0051726), pyrimidine nucleotide biosynthetic process (GO:0006221), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), transcription coactivator binding (GO:0001223), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
negative regulation of DNA-templated transcription	1
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
immune system process	1
regulation of biological process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
positive regulation of DNA-templated transcription	1
cell cycle	1
regulation of cellular process	1
pyrimidine nucleotide metabolic process	1
nucleotide biosynthetic process	1
pyrimidine-containing compound biosynthetic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
transcription coregulator binding	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
DNA binding	1
transcription factor binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cytoskeleton	1

Protein interactions and networks

STRING

440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB49	TMEM128	Q5BJH2	573
ZBTB49	MSC	O60682	456
ZBTB49	LYAR	Q9NX58	438
ZBTB49	STX18	Q9P2W9	406
ZBTB49	OTOP1	Q7RTM1	358
ZBTB49	NSG1	P42857	349
ZBTB49	THAP1	Q9NVV9	338
ZBTB49	ZNF862	O60290	327
ZBTB49	RALGAPA2	Q2PPJ7	306
ZBTB49	STK32B	Q9NY57	302
ZBTB49	MEAF6	Q9HAF1	283
ZBTB49	STRADB	Q9C0K7	279
ZBTB49	CHORDC1	Q9UHD1	277
ZBTB49	ZBTB41	Q5SVQ8	276
ZBTB49	EVC	P57679	271
ZBTB49	TAC4	Q86UU9	271

IntAct

57 interactions, top by confidence:

A	B	Type	Score
CEP70	ZBTB49	psi-mi:“MI:0915”(physical association)	0.740
ZBTB49	GOPC	psi-mi:“MI:0915”(physical association)	0.740
ZBTB49	CEP70	psi-mi:“MI:0915”(physical association)	0.740
GOPC	ZBTB49	psi-mi:“MI:0915”(physical association)	0.740
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730
ZBTB49	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	ZBTB49	psi-mi:“MI:0915”(physical association)	0.720
ZBTB49	GOPC	psi-mi:“MI:0915”(physical association)	0.560
VAC14	ZBTB49	psi-mi:“MI:0915”(physical association)	0.560
TRAF3	ZBTB49	psi-mi:“MI:0915”(physical association)	0.560
ZBTB49	PICK1	psi-mi:“MI:0915”(physical association)	0.560
ZBTB49	ZBTB2	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	ZBTB49	psi-mi:“MI:0915”(physical association)	0.560
ZBTB49	CIB1	psi-mi:“MI:0915”(physical association)	0.560
ZBTB49	ATP1A3	psi-mi:“MI:0915”(physical association)	0.560
ZBTB49	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
VHL	ZBTB49	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (42): ZBTB49 (Two-hybrid), ZBTB49 (Two-hybrid), ZBTB49 (Two-hybrid), ZBTB8A (Two-hybrid), KAT5 (Affinity Capture-Western), EP300 (Affinity Capture-Western), EP300 (Reconstituted Complex), ZBTB49 (Reconstituted Complex), ZBTB17 (FRET), ZBTB17 (Co-localization), ZBTB17 (Affinity Capture-Western), ZBTB49 (Affinity Capture-Western), HINFP (Affinity Capture-Western), ZBTB49 (Affinity Capture-Western), HINFP (Co-localization)

ESM2 similar proteins: A0A1D5NS60, A0JN76, A1YFX5, A2T7G6, A6NJL1, D2HQI1, F1MJR8, O14901, P0CG00, P10754, P22227, P98182, Q0IJ29, Q1L8W0, Q3SWU4, Q5DW34, Q5EAC5, Q5EXX3, Q5RHB5, Q5SXI5, Q5T619, Q66H04, Q6NRM8, Q6NV66, Q6ZSB9, Q7M6U3, Q7TS63, Q7TSH3, Q7ZWZ4, Q801P1, Q86VK4, Q8BKX7, Q8BXX2, Q8NAM6, Q8NAP3, Q8NCP5, Q8R0A2, Q91VW9, Q96IT1, Q96N77

Diamond homologs: A0A1B8YAB1, A1YPR0, B0WWP2, B1H285, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, C9JR72, D3Z8N4, E0CZ16, G3X9X1, O15062, O88939, O93567, O95365, P28575, P41182, P41183, Q08CL3, Q08DK3, Q13105, Q16RL8, Q2M0J9, Q3UQV5, Q52KB5, Q5EXX3, Q5R7B8, Q5RDY3, Q5TC79, Q5ZI33, Q5ZKD9, Q5ZM39, Q60821

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	96
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1647 predictions. Top by Δscore:

Variant	Effect	Δscore
4:4290351:GG:G	donor_gain	1.0000
4:4290352:GG:G	donor_gain	1.0000
4:4300035:G:GA	donor_gain	1.0000
4:4300095:TAGG:T	donor_loss	1.0000
4:4300096:AGG:A	donor_loss	1.0000
4:4300099:T:G	donor_loss	1.0000
4:4313039:A:AG	acceptor_gain	1.0000
4:4313039:A:C	acceptor_loss	1.0000
4:4313039:AG:A	acceptor_gain	1.0000
4:4313040:G:GG	acceptor_gain	1.0000
4:4313040:GG:G	acceptor_gain	1.0000
4:4313040:GGC:G	acceptor_gain	1.0000
4:4313040:GGCA:G	acceptor_gain	1.0000
4:4313112:GAG:G	donor_gain	1.0000
4:4313112:GAGGT:G	donor_loss	1.0000
4:4313113:AGGTC:A	donor_loss	1.0000
4:4313114:GG:G	donor_loss	1.0000
4:4313115:G:GA	donor_loss	1.0000
4:4313116:T:A	donor_loss	1.0000
4:4315725:C:G	donor_gain	1.0000
4:4290319:GA:G	donor_gain	0.9900
4:4290321:G:GG	donor_gain	0.9900
4:4299924:TAG:T	acceptor_loss	0.9900
4:4299925:A:AG	acceptor_gain	0.9900
4:4299925:A:G	acceptor_loss	0.9900
4:4299926:G:GG	acceptor_gain	0.9900
4:4300098:G:GG	donor_gain	0.9900
4:4300767:G:GT	donor_gain	0.9900
4:4301986:CAG:C	acceptor_loss	0.9900
4:4301987:A:AC	acceptor_loss	0.9900

AlphaMissense

5101 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:4306176:T:C	F432L	1.000
4:4306178:C:A	F432L	1.000
4:4306178:C:G	F432L	1.000
4:4313061:C:A	H441Q	1.000
4:4313061:C:G	H441Q	1.000
4:4315637:T:C	F460L	1.000
4:4315639:T:A	F460L	1.000
4:4315639:T:G	F460L	1.000
4:4315811:T:C	F488L	1.000
4:4315813:T:A	F488L	1.000
4:4315813:T:G	F488L	1.000
4:4315895:T:C	F516L	1.000
4:4315897:T:A	F516L	1.000
4:4315897:T:G	F516L	1.000
4:4320732:T:C	F572L	1.000
4:4320734:T:A	F572L	1.000
4:4320734:T:G	F572L	1.000
4:4303046:T:C	F404L	0.999
4:4303048:T:A	F404L	0.999
4:4303048:T:G	F404L	0.999
4:4303071:T:C	L412P	0.999
4:4303073:C:A	H413N	0.999
4:4303073:C:G	H413D	0.999
4:4303080:G:C	R415P	0.999
4:4303085:C:G	H417D	0.999
4:4303087:T:A	H417Q	0.999
4:4303087:T:G	H417Q	0.999
4:4306149:T:C	F423L	0.999
4:4306151:T:A	F423L	0.999
4:4306151:T:G	F423L	0.999

dbSNP variants (sampled 300 via entrez): RS1000133948 (4:4319132 A>G), RS1000159393 (4:4292113 C>G), RS1000223465 (4:4296894 G>A), RS1000312132 (4:4307904 C>G,T), RS1000466940 (4:4291941 C>T), RS1000497713 (4:4291134 G>T), RS1000502222 (4:4317945 A>G,T), RS1001085566 (4:4307358 G>C,T), RS1001111313 (4:4301041 G>A), RS1001142612 (4:4299803 G>T), RS1001368327 (4:4295912 A>G), RS1001391622 (4:4306120 T>A,C), RS1001444812 (4:4299576 G>A), RS1001552014 (4:4310877 A>G), RS1001613941 (4:4311287 A>G)

Disease associations

OMIM: gene MIM:616238 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005174_9	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	increases reaction, affects binding	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Sunitinib	increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HD00	HEK293 eGFP-ZBTB49	Transformed cell line	Female

Clinical trials (associated diseases)

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