ZNF300

Summary

ZNF300 (zinc finger protein 300, HGNC:13091) is a protein-coding gene on chromosome 5q33.1, encoding Zinc finger protein 300 (Q96RE9). Has a transcriptional repressor activity.

The protein encoded by this gene is a C2H2-type zinc finger DNA binding protein and likely transcriptional regulator. The function of this protein is not yet known. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 91975 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_052860

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13091
Approved symbol	ZNF300
Name	zinc finger protein 300
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145908
Ensembl biotype	protein_coding
OMIM	612429
Entrez	91975

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000274599, ENST00000427179, ENST00000446148

RefSeq mRNA: 3 — MANE Select: NM_052860 NM_001172831, NM_001172832, NM_052860

CCDS: CCDS4311

Canonical transcript exons

ENST00000274599 — 6 exons

Exon	Start	End
ENSE00001085705	150903864	150903977
ENSE00001517808	150898062	150898184
ENSE00003459515	150898428	150898554
ENSE00003479205	150903141	150903182
ENSE00003917875	150894399	150896973
ENSE00003918400	150904704	150904980

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 93.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.9163 / max 98.0059, expressed in 1266 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64274	1.9837	795
64272	1.4217	731
64271	1.1395	620
64273	0.3714	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	93.40	gold quality
ganglionic eminence	UBERON:0004023	93.35	gold quality
embryo	UBERON:0000922	93.34	gold quality
ventricular zone	UBERON:0003053	87.77	gold quality
calcaneal tendon	UBERON:0003701	83.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.78	gold quality
pancreatic ductal cell	CL:0002079	80.74	silver quality
left ovary	UBERON:0002119	80.68	gold quality
right ovary	UBERON:0002118	79.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.90	gold quality
ovary	UBERON:0000992	77.48	gold quality
metanephros	UBERON:0000081	76.98	gold quality
left lobe of thyroid gland	UBERON:0001120	76.71	gold quality
body of pancreas	UBERON:0001150	76.54	gold quality
stromal cell of endometrium	CL:0002255	76.52	gold quality
body of uterus	UBERON:0009853	76.52	gold quality
metanephros cortex	UBERON:0010533	76.52	gold quality
right lobe of thyroid gland	UBERON:0001119	76.10	gold quality
thyroid gland	UBERON:0002046	76.00	gold quality
epithelial cell of pancreas	CL:0000083	75.92	silver quality
endometrium	UBERON:0001295	75.59	gold quality
tibial nerve	UBERON:0001323	75.59	gold quality
smooth muscle tissue	UBERON:0001135	75.29	gold quality
ectocervix	UBERON:0012249	74.62	gold quality
descending thoracic aorta	UBERON:0002345	74.41	gold quality
ileal mucosa	UBERON:0000331	74.36	silver quality
esophagus mucosa	UBERON:0002469	74.32	gold quality
lower esophagus mucosa	UBERON:0035834	74.02	gold quality
body of stomach	UBERON:0001161	73.92	gold quality
thoracic aorta	UBERON:0001515	73.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.35

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
ALDOA
CDKN1A	Repression
CDKN1B	Repression
CXCL8	Activation
IL2RB	Activation
IL6	Activation
MYC	Activation
SPI1

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

43 targeting ZNF300, 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-4425	100.00	67.59	1049
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-5590-5P	98.81	68.78	969

Literature-anchored findings (GeneRIF, showing 10)

• ZNF-300 and novel splice variant ZNF300-B are both expressed highly in human testis. (PMID:17541838)
• Results show that the ZNF300 gene encodes a 68-kDa nuclear protein that binds DNA in a sequence-specific manner. (PMID:18350257)
• ZNF300 was activated by PU.1 and suggested that the regulation may be involved in the progression of leukemia development and hematopoietic differentiation. (PMID:20471086)
• Data show that co-expression of ZNF300 and Egr1 lead to enhanced IL-2Rbeta promoter activity, and suggest that ZNF300 is another regulator of the human IL-2Rbeta promoter. (PMID:20585888)
• A novel function for ZNF300 in tumour development was identified that may uniquely link inflammation and NF-kappa B to tumourigenesis in humans but not in mice. (PMID:21777376)
• Our findings further support ZNF300P1 as frequently methylated in ovarian cancer and reveal a novel function for ZNF300P1 lincRNA expression (PMID:24393131)
• These results suggested that ZNF300 plays an important role in hepatic lipid metabolism via PPARalpha promoting fatty acid oxidation and this effect might be blocked by DNMT3a-mediated methylation of ZNF300. (PMID:30568000)
• ZNF300 promotes chemoresistance and aggressive behaviour in non-small-cell lung cancer. (PMID:33078469)
• Cisplatin resistance and malignant behaviors of lung cancer cells are promoted by circ_0002360 via targeting miR-6751-3p to regulate the expression of ZNF300. (PMID:35166026)
• ZNF300 promotes proliferation and migration of hepatocellular carcinoma by upregulating c-MYC gene expression. (PMID:39018766)

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631), ZNF3 (ENSG00000166526)

Protein

Protein identifiers

Zinc finger protein 300 — Q96RE9 (reviewed: Q96RE9)

All UniProt accessions (2): Q96RE9, F8WE31

UniProt curated annotations — full annotation on UniProt →

Function. Has a transcriptional repressor activity.

Subunit / interactions. Interacts (via the KRAB domain) with TRIM28 (via the RBCC domain).

Subcellular location. Nucleus.

Tissue specificity. Expressed mostly in heart, skeletal muscle and brain. Isoform 1 and isoform 2 are highly expressed in testis.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q96RE9-1	1	yes
Q96RE9-2	2, Zinc finger protein 300-B, ZNF300B
Q96RE9-3	3
Q96RE9-4	4

RefSeq proteins (3): NP_001166302, NP_001166303, NP_443092* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF01352

UniProt features (21 total): zinc finger region 12, splice variant 3, sequence conflict 2, chain 1, domain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RE9-F1	68.40	0.47

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 39 (showing top): GOCC_NUCLEOLUS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, FOXE1_TARGET_GENES, SKIL_TARGET_GENES, ZNF512_TARGET_GENES, ZNF8_TARGET_GENES, MIR548P, MIR6124, MIR4755_5P, MIR5006_3P, MIR520E_5P

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
nuclear lumen	2
intracellular membraneless organelle	2
regulation of DNA-templated transcription	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
nucleoplasm	1

Protein interactions and networks

STRING

494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF300	IRGM	A1A4Y4	826
ZNF300	SLC26A1	Q9H2B4	435
ZNF300	IKBKB	O14920	428
ZNF300	PRRT4	C9JH25	399
ZNF300	GRHPR	Q9UBQ7	360
ZNF300	SMIM3	Q9BZL3	353
ZNF300	PUS7L	Q9H0K6	348
ZNF300	NKX2-4	Q9H2Z4	348
ZNF300	SHISA7	A6NL88	325
ZNF300	PP2D1	A8MPX8	321
ZNF300	ETV3	P41162	298
ZNF300	PHACTR2	O75167	298
ZNF300	ETV7	Q9Y603	295
ZNF300	GAPDHS	O14556	285
ZNF300	SPDEF	O95238	283

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SLC9A8	ZNF432	psi-mi:“MI:0914”(association)	0.530
C9orf72	CHD2	psi-mi:“MI:0914”(association)	0.350
SLC9A8	AP1G1	psi-mi:“MI:0914”(association)	0.350
E2F3	MYO1C	psi-mi:“MI:0914”(association)	0.350
	ZNF300	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): ZNF300 (Synthetic Growth Defect), ALX1 (Two-hybrid), ZNF300 (Affinity Capture-RNA), ZNF300 (Affinity Capture-MS), ZNF300 (Affinity Capture-MS), ZNF300 (Synthetic Lethality), ZNF300 (Affinity Capture-MS), ZNF300 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WUV0, A0JNB1, A2VDP4, B2RUI1, P0CG31, P10072, P17025, P17036, P17097, P18733, P51814, Q08ER8, Q09FC8, Q0VGE8, Q14590, Q15937, Q16600, Q2M3X9, Q4V8A8, Q5CZA5, Q5R8G9, Q5RBX0, Q5VIY5, Q68DI1, Q6J6I6, Q6NX49, Q6P1L6, Q6PG37, Q6ZMS4, Q6ZMW2, Q80YP6, Q86UD4, Q86Y25, Q8IZ26, Q8N184, Q8NB42, Q8NEK5, Q8TAF7, Q8TF47, Q8WXB4

Diamond homologs: A0A1W2PQL4, A0JNB1, A0JPL0, A6NK53, A6QLU5, A6QPT6, A7MBI1, A8MT65, A8MUV8, A8MWA4, B2RXC5, B4DU55, B4DX44, E9PYI1, O14628, O75346, P0CH99, P0CI00, P17014, P17030, P17032, P17098, P51786, P85977, Q02386, Q06730, Q06732, Q0VAW7, Q12901, Q13360, Q14586, Q14588, Q14590, Q16587, Q2M3X9, Q2VY69, Q32M78, Q3ZCX4, Q49AA0, Q4R6J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

680 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150898056:A:AC	donor_gain	1.0000
5:150898057:C:CC	donor_gain	1.0000
5:150898059:T:TA	donor_gain	1.0000
5:150898115:C:CA	donor_gain	1.0000
5:150898181:TACC:T	acceptor_gain	1.0000
5:150898183:CC:C	acceptor_gain	1.0000
5:150898184:CCTAT:C	acceptor_gain	1.0000
5:150898185:C:CA	acceptor_loss	1.0000
5:150898185:C:CC	acceptor_gain	1.0000
5:150903183:C:CC	acceptor_gain	1.0000
5:150904794:C:A	donor_gain	1.0000
5:150904810:T:A	donor_gain	1.0000
5:150904817:T:TA	donor_gain	1.0000
5:150896970:CTGT:C	acceptor_gain	0.9900
5:150898072:ATCTG:A	donor_gain	0.9900
5:150898076:G:A	donor_gain	0.9900
5:150898088:T:C	donor_gain	0.9900
5:150898182:ACC:A	acceptor_gain	0.9900
5:150898183:CCC:C	acceptor_gain	0.9900
5:150898185:C:T	acceptor_gain	0.9900
5:150898188:T:C	acceptor_gain	0.9900
5:150898188:T:TC	acceptor_gain	0.9900
5:150898422:CCTTA:C	donor_loss	0.9900
5:150898423:CTTAC:C	donor_loss	0.9900
5:150898424:TTA:T	donor_loss	0.9900
5:150898425:TA:T	donor_loss	0.9900
5:150898426:A:AC	donor_gain	0.9900
5:150898426:ACCC:A	donor_loss	0.9900
5:150898427:C:CC	donor_gain	0.9900
5:150903136:CTCA:C	donor_loss	0.9900

AlphaMissense

4013 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150895985:G:C	F418L	0.999
5:150895985:G:T	F418L	0.999
5:150895987:A:G	F418L	0.999
5:150896153:G:C	F362L	0.999
5:150896153:G:T	F362L	0.999
5:150896155:A:G	F362L	0.999
5:150895649:G:C	F530L	0.998
5:150895649:G:T	F530L	0.998
5:150895651:A:G	F530L	0.998
5:150895733:G:C	F502L	0.998
5:150895733:G:T	F502L	0.998
5:150895735:A:G	F502L	0.998
5:150895968:A:G	L424P	0.998
5:150896069:A:C	F390L	0.998
5:150896069:A:T	F390L	0.998
5:150896071:A:G	F390L	0.998
5:150895716:A:G	L508P	0.997
5:150895901:G:C	F446L	0.997
5:150895901:G:T	F446L	0.997
5:150895903:A:G	F446L	0.997
5:150896052:A:G	L396P	0.997
5:150896136:A:G	L368P	0.997
5:150896237:G:C	F334L	0.997
5:150896237:G:T	F334L	0.997
5:150896239:A:G	F334L	0.997
5:150895481:G:C	F586L	0.996
5:150895481:G:T	F586L	0.996
5:150895483:A:G	F586L	0.996
5:150895565:A:C	F558L	0.996
5:150895565:A:T	F558L	0.996

dbSNP variants (sampled 300 via entrez): RS1000009084 (5:150900856 C>T), RS1000595499 (5:150893954 T>G), RS1000985387 (5:150900677 G>A), RS1001319263 (5:150899249 C>G), RS1001336795 (5:150902783 G>A), RS1001605671 (5:150899543 T>C), RS1001677733 (5:150899221 C>T), RS1002189620 (5:150906290 C>G), RS1002515755 (5:150902897 T>C), RS1002869510 (5:150904229 A>T), RS1002978195 (5:150897586 T>C), RS1003281439 (5:150897817 A>G), RS1003311736 (5:150896111 A>T), RS1003338911 (5:150897475 G>A), RS1003446314 (5:150904776 T>C)

Disease associations

OMIM: gene MIM:612429 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19
GCST005758_8	Dimensional psychopathology (Arousal)	5.000000e-07
GCST005855_1	Cholangiocarcinoma in primary sclerosing cholangitis	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009099	arousal domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
arsenite	decreases expression, increases methylation	1
methylparaben	decreases expression	1
potassium chromate(VI)	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects expression, affects methylation	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Vanadates	increases expression	1
Cyclosporine	affects expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XW30	HEK293 eGFP-ZNF300	Transformed cell line	Female

Clinical trials (associated diseases)

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