ZBTB7C

Summary

ZBTB7C (zinc finger and BTB domain containing 7C, HGNC:31700) is a protein-coding gene on chromosome 18q21.1, encoding Zinc finger and BTB domain-containing protein 7C (A1YPR0). May be a tumor suppressor gene.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of cell population proliferation. Predicted to be located in nucleus.

Source: NCBI Gene 201501 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_001318841

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31700
Approved symbol	ZBTB7C
Name	zinc finger and BTB domain containing 7C
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ZNF857C
Ensembl gene	ENSG00000184828
Ensembl biotype	protein_coding
OMIM	616591
Entrez	201501

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 38 protein_coding

ENST00000535628, ENST00000585404, ENST00000586047, ENST00000586438, ENST00000586525, ENST00000586743, ENST00000587107, ENST00000588028, ENST00000588053, ENST00000588149, ENST00000588566, ENST00000588970, ENST00000588982, ENST00000589077, ENST00000589170, ENST00000589194, ENST00000589619, ENST00000590178, ENST00000590374, ENST00000590437, ENST00000590800, ENST00000590855, ENST00000591279, ENST00000591405, ENST00000591526, ENST00000592387, ENST00000592656, ENST00000593159, ENST00000868923, ENST00000868924, ENST00000868925, ENST00000868926, ENST00000868927, ENST00000868928, ENST00000868929, ENST00000868930, ENST00000971936, ENST00000971937

RefSeq mRNA: 9 — MANE Select: NM_001318841 NM_001039360, NM_001318841, NM_001371284, NM_001371285, NM_001371286, NM_001371287, NM_001371288, NM_001371290, NM_001371291

CCDS: CCDS32830

Canonical transcript exons

ENST00000590800 — 5 exons

Exon	Start	End
ENSE00001307737	48039900	48041123
ENSE00002744375	48185934	48185995
ENSE00002793715	48338174	48338398
ENSE00002874498	48409226	48409383
ENSE00003844340	48026672	48029911

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 90.15.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1842 / max 131.8059, expressed in 472 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171857	0.8969	202
171864	0.8940	327
171856	0.1195	60
171862	0.0968	46
171858	0.0510	28
171861	0.0449	19
171859	0.0416	21
171860	0.0331	12
171863	0.0064	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mammalian vulva	UBERON:0000997	90.15	gold quality
esophagus mucosa	UBERON:0002469	90.02	gold quality
bronchial epithelial cell	CL:0002328	89.73	gold quality
gingiva	UBERON:0001828	89.71	gold quality
lower esophagus mucosa	UBERON:0035834	89.65	gold quality
gingival epithelium	UBERON:0001949	89.48	gold quality
esophagus squamous epithelium	UBERON:0006920	88.85	gold quality
nipple	UBERON:0002030	88.48	gold quality
colonic mucosa	UBERON:0000317	88.01	gold quality
pharyngeal mucosa	UBERON:0000355	87.52	gold quality
oral cavity	UBERON:0000167	87.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.09	gold quality
mucosa of transverse colon	UBERON:0004991	86.33	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.33	silver quality
skin of leg	UBERON:0001511	85.71	gold quality
sural nerve	UBERON:0015488	85.62	gold quality
upper leg skin	UBERON:0004262	85.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.99	gold quality
corpus epididymis	UBERON:0004359	84.85	gold quality
skin of abdomen	UBERON:0001416	84.65	gold quality
zone of skin	UBERON:0000014	84.37	gold quality
calcaneal tendon	UBERON:0003701	84.35	gold quality
vagina	UBERON:0000996	84.00	gold quality
right lobe of thyroid gland	UBERON:0001119	83.96	gold quality
left lobe of thyroid gland	UBERON:0001120	83.81	gold quality
thyroid gland	UBERON:0002046	83.70	gold quality
penis	UBERON:0000989	83.69	gold quality
adrenal tissue	UBERON:0018303	83.07	gold quality
right adrenal gland cortex	UBERON:0035827	82.90	gold quality
rectum	UBERON:0001052	82.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	25.90
E-ANND-3	yes	9.50

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CDKN1A	Unknown
FASN
NOTCH1

JASPAR motifs

Motif	Name	Family
MA0695.1	ZBTB7C	More than 3 adjacent zinc fingers
MA0695.2	ZBTB7C	More than 3 adjacent zinc fingers
MA0695.3	ZBTB7C	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:19443739

miRNA regulators (miRDB)

116 targeting ZBTB7C, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 7)

• Adm and APM-1 protect endothelium-dependent vascular relaxation in sepsis. (PMID:17932560)
• our findings define KR-POK as a transcriptional repressor with a pro-oncogenic role that relies upon binding to p53 and inhibition of its transactivation function. (PMID:22253232)
• ZBTB7C genetic variations were significant for susceptibility to ischemic injury in cerebral ischemia. (PMID:26542693)
• Repression of Kr-POK inhibited tumor growth. (PMID:28571744)
• Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data. (PMID:32193444)
• The prognostic and immunological effects of ZBTB7C across cancers: friend or foe? (PMID:33946045)
• ZBTB7C m6A modification incurred by METTL3 aberration promotes osteosarcoma progression. (PMID:37121538)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb7c	ENSDARG00000100985
mus_musculus	Zbtb7c	ENSMUSG00000044646
rattus_norvegicus	Zbtb7c	ENSRNOG00000047924

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 7C — A1YPR0 (reviewed: A1YPR0)

Alternative names: Affected by papillomavirus DNA integration in ME180 cells protein 1, Zinc finger and BTB domain-containing protein 36, Zinc finger protein 857C

All UniProt accessions (6): A0A1B0GXF8, A1YPR0, B2RG49, B2RG53, B2RG63, B2RG76

UniProt curated annotations — full annotation on UniProt →

Function. May be a tumor suppressor gene.

Tissue specificity. Detected in normal cervical keratinocytes, and in some cervical carcinoma cell lines.

RefSeq proteins (9): NP_001034449, NP_001305770, NP_001358213, NP_001358214, NP_001358215, NP_001358216, NP_001358217, NP_001358219, NP_001358220 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050457	ZnFinger_BTB_dom_contain	Family

Pfam: PF00096, PF00651

UniProt features (9 total): zinc finger region 4, compositionally biased region 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1YPR0-F1	56.80	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_FAT_CELL_DIFFERENTIATION, CUI_TCF21_TARGETS_2_DN, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, chr18q21, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, PKCA_DN.V1_UP, ESC_J1_UP_EARLY.V1_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of cell population proliferation (GO:0008285), positive regulation of fat cell differentiation (GO:0045600), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
fat cell differentiation	1
positive regulation of cell differentiation	1
regulation of fat cell differentiation	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB7C	MALRD1	Q5VYJ5	461
ZBTB7C	CTIF	O43310	444
ZBTB7C	CLIP3	Q96DZ5	443
ZBTB7C	TP53	P04637	436
ZBTB7C	CHST8	Q9H2A9	427
ZBTB7C	CCDC60	Q8IWA6	413
ZBTB7C	PHKB	Q93100	412
ZBTB7C	ADCY7	P51828	410
ZBTB7C	PCF11	O94913	400
ZBTB7C	CIDEC	Q96AQ7	391
ZBTB7C	APLP1	P51693	387
ZBTB7C	THSD4	Q6ZMP0	383
ZBTB7C	SLCO6A1	Q86UG4	376
ZBTB7C	CSF2	P04141	375
ZBTB7C	CXCL8	P10145	375
ZBTB7C	RABEP2	Q9H5N1	375

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RETREG1	ZBTB7C	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ZBTB7C	ZBTB5	psi-mi:“MI:0914”(association)	0.350
CDC5L		psi-mi:“MI:0914”(association)	0.350

BioGRID (25): ZBTB7C (Affinity Capture-MS), JUN (Affinity Capture-Western), ZBTB7C (Affinity Capture-Western), JUN (Reconstituted Complex), ZBTB17 (Affinity Capture-Western), ZBTB7C (Reconstituted Complex), ZBTB17 (Reconstituted Complex), ZBTB7C (FRET), ZBTB7C (Affinity Capture-Western), PIAS1 (Affinity Capture-Western), ZBTB7C (Affinity Capture-Western), PIAS1 (Co-purification), ZBTB7C (Affinity Capture-MS), GATAD2B (Affinity Capture-MS), KLHL29 (Affinity Capture-MS)

ESM2 similar proteins: A0PJY2, A1YPR0, A2A935, B0K011, B0X9H6, B7ZRU9, O13089, O15090, O15156, O75626, O88939, O93567, O95365, P14404, P25932, P41183, P56260, Q03112, Q08DS3, Q0IHB8, Q1L8W0, Q2VWH6, Q32NK7, Q3T135, Q5XJQ7, Q60636, Q64321, Q6AY34, Q6DBW0, Q6F2E4, Q802Y8, Q8I7Z8, Q8K083, Q8N9L1, Q8NAP8, Q8TBJ5, Q8VCZ7, Q8VDL9, Q98T94, Q99PV8

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1139 predictions. Top by Δscore:

Variant	Effect	Δscore
18:48029908:CTGC:C	acceptor_gain	1.0000
18:48029909:TGC:T	acceptor_gain	1.0000
18:48029910:GC:G	acceptor_gain	1.0000
18:48029911:CC:C	acceptor_gain	1.0000
18:48029912:C:CC	acceptor_gain	1.0000
18:48029917:A:AC	acceptor_gain	0.9900
18:48041119:GAGCC:G	acceptor_gain	0.9900
18:48041121:GCC:G	acceptor_gain	0.9900
18:48041122:CC:C	acceptor_gain	0.9900
18:48041122:CCC:C	acceptor_gain	0.9900
18:48041123:CC:C	acceptor_gain	0.9900
18:48041123:CCTGC:C	acceptor_loss	0.9900
18:48041124:C:CC	acceptor_gain	0.9900
18:48041124:CTG:C	acceptor_loss	0.9900
18:48041125:T:A	acceptor_loss	0.9900
18:48096670:A:AC	donor_gain	0.9900
18:48096671:C:CC	donor_gain	0.9900
18:48135812:T:TA	donor_gain	0.9900
18:48029915:C:CT	acceptor_gain	0.9800
18:48029917:A:C	acceptor_gain	0.9800
18:48041120:AGCC:A	acceptor_gain	0.9800
18:48041135:C:CT	acceptor_gain	0.9800
18:48113646:T:C	acceptor_gain	0.9800
18:48137002:CCCA:C	donor_loss	0.9800
18:48137003:CCA:C	donor_loss	0.9800
18:48137004:CAC:C	donor_loss	0.9800
18:48137006:C:CT	donor_loss	0.9800
18:48029916:A:T	acceptor_gain	0.9700
18:48041127:C:CT	acceptor_gain	0.9700
18:48072587:T:C	acceptor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011 (18:48328680 C>T), RS1000011950 (18:48241047 C>A), RS1000012436 (18:48370657 GA>G,GAA), RS1000027935 (18:48117598 G>C,T), RS1000040228 (18:48041967 C>A), RS1000044048 (18:48191519 G>A), RS1000057599 (18:48083023 G>C), RS1000071026 (18:48123251 A>T), RS1000086384 (18:48109589 A>G,T), RS1000092841 (18:48237425 G>A), RS1000098980 (18:48295100 C>G,T), RS1000112532 (18:48072280 C>A), RS1000113216 (18:48100083 G>A), RS1000121744 (18:48205907 C>T), RS1000128659 (18:48164829 A>C)

Disease associations

OMIM: gene MIM:616591 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004025_6	Systemic juvenile idiopathic arthritis	6.000000e-07
GCST004749_49	Lung cancer in ever smokers	8.000000e-06
GCST006979_272	Heel bone mineral density	3.000000e-09
GCST006979_273	Heel bone mineral density	1.000000e-13
GCST007843_27	Rheumatoid arthritis	7.000000e-09
GCST008062_73	Blood urea nitrogen levels	2.000000e-14
GCST008152_187	Weight	9.000000e-06
GCST008758_75	Pre-treatment viral load in HIV-1 infection	5.000000e-16
GCST008839_255	Height	2.000000e-08
GCST010989_281	Body size at age 10	2.000000e-21
GCST012145_10	Ferritin levels	6.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004338	body weight
EFO:0010125	viral load
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004459	ferritin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Valproic Acid	increases methylation, affects expression	2
Aflatoxin B1	increases methylation, decreases expression, decreases methylation	2
perfluorotetradecanoic acid	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
sodium arsenate	increases abundance, decreases expression	1
beta-lapachone	decreases expression	1
perfluorooctanoic acid	affects expression	1
aflatoxin B2	increases methylation	1
perfluorobutyric acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Arsenic	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethinyl Estradiol	decreases expression	1
Lead	affects expression	1
Smoke	decreases expression	1
Triclosan	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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