ZBTB39

Summary

ZBTB39 (zinc finger and BTB domain containing 39, HGNC:29014) is a protein-coding gene on chromosome 12q13.3, encoding Zinc finger and BTB domain-containing protein 39 (O15060). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Predicted to be located in nucleus. Predicted to be active in nucleoplasm.

Source: NCBI Gene 9880 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 108 total
• MANE Select transcript: NM_014830

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29014
Approved symbol	ZBTB39
Name	zinc finger and BTB domain containing 39
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0352, ZNF922
Ensembl gene	ENSG00000166860
Ensembl biotype	protein_coding
OMIM	619384
Entrez	9880

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000300101, ENST00000945714

RefSeq mRNA: 1 — MANE Select: NM_014830 NM_014830

CCDS: CCDS31839

Canonical transcript exons

ENST00000300101 — 2 exons

Exon	Start	End
ENSE00001107272	56998836	57004961
ENSE00001415803	57006405	57006546

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 90.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5861 / max 48.7986, expressed in 1627 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131612	4.2752	1523
131611	1.3109	753

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	90.55	gold quality
secondary oocyte	CL:0000655	90.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.09	gold quality
ventricular zone	UBERON:0003053	75.40	gold quality
stromal cell of endometrium	CL:0002255	73.98	gold quality
ganglionic eminence	UBERON:0004023	73.85	gold quality
granulocyte	CL:0000094	72.48	gold quality
pancreatic ductal cell	CL:0002079	72.40	silver quality
monocyte	CL:0000576	72.37	gold quality
leukocyte	CL:0000738	72.34	gold quality
mononuclear cell	CL:0000842	72.16	gold quality
cortical plate	UBERON:0005343	71.98	gold quality
sperm	CL:0000019	71.41	silver quality
islet of Langerhans	UBERON:0000006	71.33	gold quality
embryo	UBERON:0000922	70.68	gold quality
lymph node	UBERON:0000029	70.34	gold quality
spleen	UBERON:0002106	70.18	gold quality
male germ cell	CL:0000015	69.73	silver quality
lower esophagus	UBERON:0013473	69.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	69.31	gold quality
testis	UBERON:0000473	69.21	gold quality
right testis	UBERON:0004534	69.21	gold quality
pancreas	UBERON:0001264	68.91	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	68.79	gold quality
left uterine tube	UBERON:0001303	68.65	gold quality
right lobe of liver	UBERON:0001114	68.58	gold quality
smooth muscle tissue	UBERON:0001135	68.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	68.44	gold quality
body of stomach	UBERON:0001161	68.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

251 targeting ZBTB39, 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-9-5P	100.00	72.28	2361
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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb39	ENSDARG00000019265
mus_musculus	Zbtb39	ENSMUSG00000044617
rattus_norvegicus	Zbtb39	ENSRNOG00000004306
drosophila_melanogaster	CG12769	FBGN0033252
caenorhabditis_elegans		WBGENE00001223
caenorhabditis_elegans		WBGENE00017406
caenorhabditis_elegans		WBGENE00019960

Paralogs (7): ZNF423 (ENSG00000102935), ZNF211 (ENSG00000121417), ZNF462 (ENSG00000148143), ZNF597 (ENSG00000167981), ZNF445 (ENSG00000185219), ZNF786 (ENSG00000197362), ZNF521 (ENSG00000198795)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 39 — O15060 (reviewed: O15060)

All UniProt accessions (1): O15060

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_055645* (*=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
IPR047989	ZBTB39_BTB_POZ	Domain

Pfam: PF00096, PF00651

UniProt features (17 total): zinc finger region 8, region of interest 3, cross-link 2, chain 1, domain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15060-F1	51.90	0.00

Functional residue map

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

Post-translational modifications (2): 183, 439

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 137 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, CAGCAGG_MIR370, GOBP_CYTOKINE_PRODUCTION, ATTCTTT_MIR186, ATGCTGG_MIR338, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, CCAGGGG_MIR331, TGCCTTA_MIR124A, CAGCCTC_MIR4855P, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, CTGTTAC_MIR194, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, EPPERT_LSC_R, CACTGCC_MIR34A_MIR34C_MIR449

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cytokine production (GO:0001817), regulation of immune system process (GO:0002682)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleoplasm (GO:0005654), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
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
cis-regulatory region sequence-specific DNA 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
nucleic acid binding	1
binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

668 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB39	RNF166	Q96A37	646
ZBTB39	CSRNP2	Q9H175	543
ZBTB39	ZNF827	Q17R98	529
ZBTB39	SACK1F	Q8NEG4	507
ZBTB39	DTWD1	Q8N5C7	475
ZBTB39	CRBN	Q96SW2	468
ZBTB39	ESYT1	Q9BSJ8	459
ZBTB39	MATCAP2	Q8NCT3	458
ZBTB39	ANKRD52	Q8NB46	448
ZBTB39	RAB28	P51157	431
ZBTB39	NAV3	Q8IVL0	423
ZBTB39	TARBP2	Q15633	415
ZBTB39	WIZ	O95785	402
ZBTB39	TMEM200B	Q69YZ2	400
ZBTB39	IL20RA	Q9UHF4	376

IntAct

43 interactions, top by confidence:

A	B	Type	Score
ZBTB39	TSGA10	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	TCEANC	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	KDM1A	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	PSMD2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	GAS8	psi-mi:“MI:0915”(physical association)	0.560
PLK4	ZBTB39	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	AQP1	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	SUMO3	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	IL16	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	TRIM41	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	SUMO2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB39	FOXK2	psi-mi:“MI:0914”(association)	0.530
ZBTB39	FOXK1	psi-mi:“MI:0914”(association)	0.350
GRHL1	POLRMT	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
FAM86C1P	ZBTB39	psi-mi:“MI:0914”(association)	0.350
AOPEP	ZBTB39	psi-mi:“MI:0914”(association)	0.350
AIM2	DDX39A	psi-mi:“MI:0914”(association)	0.350
TSGA10	ZBTB39	psi-mi:“MI:0915”(physical association)	0.000
TCEANC	ZBTB39	psi-mi:“MI:0915”(physical association)	0.000
KDM1A	ZBTB39	psi-mi:“MI:0915”(physical association)	0.000
PSMD2	ZBTB39	psi-mi:“MI:0915”(physical association)	0.000
GAS8	ZBTB39	psi-mi:“MI:0915”(physical association)	0.000
PLK4	ZBTB39	psi-mi:“MI:0915”(physical association)	0.000
AQP1	ZBTB39	psi-mi:“MI:0915”(physical association)	0.000
SUMO2	ZBTB39	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): NARFL (Affinity Capture-MS), FOXK2 (Affinity Capture-MS), FOXK1 (Affinity Capture-MS), ZBTB39 (Affinity Capture-MS), ZBTB39 (Two-hybrid), ZBTB39 (Two-hybrid), ZBTB39 (Two-hybrid), ZBTB39 (Two-hybrid), ZBTB39 (Two-hybrid), IL16 (Two-hybrid), PSMD2 (Two-hybrid), TCEANC (Two-hybrid), SUMO3 (Two-hybrid), SUMO2 (Two-hybrid), AQP1 (Two-hybrid)

ESM2 similar proteins: A0A1D5NS60, A0JN76, A1L2U9, B1WAZ8, E9Q3T6, O15060, O15062, O35260, O93567, P41182, P41183, Q05516, Q0IH98, Q0IJ29, Q0P4X6, Q0V8G8, Q1L8W0, Q3B725, Q3B7N9, Q3SWU4, Q5EAC5, Q5EXX3, Q5R5N5, Q5SW75, Q5ZM39, Q6DDV0, Q6NRK3, Q6NRM8, Q6ZSB9, Q7TQG0, Q7TS63, Q7TSZ8, Q7ZWZ4, Q801P1, Q80X44, Q86VK4, Q8BKX7, Q8BXX2, Q8CII0, Q8NAP3

Diamond homologs: A0A2R8Q1W5, A0JN76, A1YPR0, A6QQY2, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, D3ZUU2, D4A2K4, E1B932, F1LZF0, O14867, O15060, O43167, O43829, O88282, O88939, O93567, O95198, O95365, O95625, P17789, P42282, P57790, P97302, P97303, Q04652, Q05516, Q08376, Q08DS0, Q13105, Q14145, Q1ECZ2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

249 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57006404:CCCGG:C	donor_gain	1.0000
12:57006062:T:TA	donor_gain	0.9900
12:57006399:GCTT:G	donor_loss	0.9900
12:57006400:CTTA:C	donor_loss	0.9900
12:57006401:TTA:T	donor_loss	0.9900
12:57006402:TACC:T	donor_loss	0.9900
12:57006403:A:AC	donor_gain	0.9900
12:57006403:AC:A	donor_gain	0.9900
12:57006404:C:CC	donor_gain	0.9900
12:57006404:C:CG	donor_loss	0.9900
12:57006404:CC:C	donor_gain	0.9900
12:57002797:ATCCG:A	donor_gain	0.9800
12:57006101:C:A	donor_gain	0.9700
12:57004962:C:CC	acceptor_gain	0.9600
12:57004957:TTAAT:T	acceptor_gain	0.9500
12:57004958:TAAT:T	acceptor_gain	0.9500
12:57004961:TCTGT:T	acceptor_loss	0.9500
12:57004962:CT:C	acceptor_loss	0.9500
12:57006116:T:C	donor_gain	0.9400
12:57006152:C:CA	donor_gain	0.9400
12:57002798:T:C	donor_gain	0.9100
12:57006063:C:A	donor_gain	0.8900
12:57002711:CAA:C	donor_gain	0.8700
12:57006100:C:CA	donor_gain	0.8700
12:57002714:CACCT:C	donor_gain	0.8600
12:57002733:T:TA	donor_gain	0.8600
12:57004959:AAT:A	acceptor_gain	0.8600
12:57004960:AT:A	acceptor_gain	0.8600
12:57006404:CCCG:C	donor_gain	0.8600
12:57005912:C:CA	donor_gain	0.8500

AlphaMissense

4774 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57002965:G:C	H651Q	1.000
12:57002965:G:T	H651Q	1.000
12:57002967:G:C	H651D	1.000
12:57002992:A:C	F642L	1.000
12:57002992:A:T	F642L	1.000
12:57002993:A:G	F642S	1.000
12:57002994:A:G	F642L	1.000
12:57003004:G:C	C638W	1.000
12:57003005:C:T	C638Y	1.000
12:57003006:A:G	C638R	1.000
12:57003013:A:C	C635W	1.000
12:57003015:A:G	C635R	1.000
12:57003037:G:C	H627Q	1.000
12:57003037:G:T	H627Q	1.000
12:57003039:G:C	H627D	1.000
12:57003051:G:C	H623D	1.000
12:57003051:G:T	H623N	1.000
12:57003059:A:G	F620S	1.000
12:57003076:A:C	F614L	1.000
12:57003076:A:T	F614L	1.000
12:57003077:A:G	F614S	1.000
12:57003078:A:G	F614L	1.000
12:57003090:A:G	C610R	1.000
12:57002920:A:C	C666W	0.999
12:57002921:C:T	C666Y	0.999
12:57002922:A:G	C666R	0.999
12:57002929:G:C	C663W	0.999
12:57002931:A:G	C663R	0.999
12:57002953:G:C	H655Q	0.999
12:57002953:G:T	H655Q	0.999

dbSNP variants (sampled 300 via entrez): RS1001627229 (12:57008239 C>T), RS1002563611 (12:56999040 G>A), RS1002699514 (12:56998817 G>C), RS1002987967 (12:57007916 G>A), RS1003057667 (12:57008223 C>T), RS1003628490 (12:57001998 G>C,T), RS1004209507 (12:57003044 C>T), RS1004542997 (12:57004414 A>G,T), RS1004655928 (12:57004731 C>T), RS1004881552 (12:57002301 T>C), RS1005441593 (12:57008354 C>T), RS1005738501 (12:57002130 T>C,G), RS1006546570 (12:57008372 A>G), RS1006616133 (12:57004933 G>T), RS1006676516 (12:57004253 G>A,C)

Disease associations

OMIM: gene MIM:619384 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003831_2	Asthma	1.000000e-06
GCST007563_7	Allergic disease (asthma, hay fever or eczema)	1.000000e-09
GCST007564_27	Asthma or allergic disease (pleiotropy)	8.000000e-13
GCST008916_110	Asthma	1.000000e-27
GCST008916_18	Asthma	8.000000e-18
GCST008916_2	Asthma	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	3
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases abundance, increases expression, affects cotreatment	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pomalidomide	decreases expression, increases degradation	1
dorsomorphin	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Tretinoin	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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