ZNF580

Summary

ZNF580 (zinc finger protein 580, HGNC:29473) is a protein-coding gene on chromosome 19q13.42, encoding Zinc finger protein 580 (Q9UK33). Involved in the regulation of endothelial cell proliferation and migration.

Enables sequence-specific double-stranded DNA binding activity. Involved in several processes, including cellular response to hydrogen peroxide; positive regulation of cell migration; and positive regulation of interleukin-8 production. Located in nucleoplasm.

Source: NCBI Gene 51157 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_207115

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29473
Approved symbol	ZNF580
Name	zinc finger protein 580
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213015
Ensembl biotype	protein_coding
OMIM	617888
Entrez	51157

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000325333, ENST00000543039, ENST00000545125, ENST00000590190, ENST00000592461, ENST00000592881, ENST00000899986, ENST00000899987

RefSeq mRNA: 3 — MANE Select: NM_207115 NM_001163423, NM_016202, NM_207115

CCDS: CCDS12931

Canonical transcript exons

ENST00000325333 — 2 exons

Exon	Start	End
ENSE00002763370	55641002	55641183
ENSE00003849264	55642497	55643470

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 96.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.1934 / max 215.3042, expressed in 1811 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177657	28.1466	1807
177653	8.8448	1683
177658	4.6405	1632
177656	2.0566	1195
177659	0.6870	453
177660	0.6073	339
177654	0.2208	88
177655	0.1364	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	96.05	gold quality
right lobe of thyroid gland	UBERON:0001119	96.03	gold quality
pituitary gland	UBERON:0000007	95.79	gold quality
left lobe of thyroid gland	UBERON:0001120	95.53	gold quality
right ovary	UBERON:0002118	95.04	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.78	gold quality
apex of heart	UBERON:0002098	94.74	gold quality
lower esophagus	UBERON:0013473	94.74	gold quality
body of uterus	UBERON:0009853	94.65	gold quality
thyroid gland	UBERON:0002046	94.64	gold quality
endocervix	UBERON:0000458	94.62	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.57	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.57	gold quality
left ovary	UBERON:0002119	94.44	gold quality
CA1 field of hippocampus	UBERON:0003881	94.44	silver quality
left uterine tube	UBERON:0001303	94.39	gold quality
left coronary artery	UBERON:0001626	94.27	gold quality
popliteal artery	UBERON:0002250	94.22	gold quality
tibial artery	UBERON:0007610	94.21	gold quality
metanephros cortex	UBERON:0010533	94.20	gold quality
coronary artery	UBERON:0001621	94.17	gold quality
aorta	UBERON:0000947	94.16	gold quality
ascending aorta	UBERON:0001496	94.16	gold quality
thoracic aorta	UBERON:0001515	94.16	gold quality
right coronary artery	UBERON:0001625	93.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.70	gold quality
descending thoracic aorta	UBERON:0002345	93.60	gold quality
ectocervix	UBERON:0012249	93.56	gold quality
left adrenal gland cortex	UBERON:0035825	93.25	gold quality
renal medulla	UBERON:0000362	93.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.21
E-MTAB-6386	no	197.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting ZNF580, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-6732-5P	93.97	64.65	422

Literature-anchored findings (GeneRIF, showing 5)

• These results elucidate the important role that ZNF580 plays in the process of migration and proliferation of endothelial cells, which provides a foundation for a novel approach to regulate angiogenesis. (PMID:20382120)
• ZNF580 is a novel factor in the lipoprotein-dependent regulation of endothelial IL-8 expression and monocyte arrest. (PMID:21310414)
• ZNF580 is a binding partner of Smad2 and is involved in the signal transduction of the transforming growth factor-beta signalling pathway. (PMID:21599657)
• H2O2 upregulates the expression of ZNF580 via the NF-kappaB signaling pathway, and overexpression of ZNF580 plays a critical role in augmenting the release of pro-inflammatory cytokine IL-8. (PMID:21830064)
• These results suggest that ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-b1/ALK5/Smad2 pathway, and thus plays a crucial role in vascular endothelial cells. (PMID:24771066)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp580	ENSMUSG00000055633
rattus_norvegicus	Zfp580	ENSRNOG00000016274

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), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger protein 580 — Q9UK33 (reviewed: Q9UK33)

Alternative names: LDL-induced EC protein

All UniProt accessions (4): Q9UK33, K7EJ53, K7ENY2, K7ERU0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of endothelial cell proliferation and migration. Mediates H(2)O(2)-induced leukocyte chemotaxis by elevating interleukin-8 production and may play a role in inflammation. May be involved in transcriptional regulation.

Subunit / interactions. Interacts with SMAD2.

Subcellular location. Nucleus.

Tissue specificity. Expressed in endothelial cells.

Induction. Up-regulated in presence of reactive oxygen species (ROS), like H(2)O(2), through the NF-kappaB signaling pathway. Up-regulated by sphingosine-1-phosphate (SP1) through the p38 MAPK signaling pathway (at protein level).

RefSeq proteins (3): NP_001156895, NP_057286, NP_996998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (10 total): zinc finger region 3, compositionally biased region 3, cross-link 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK33-F1	64.93	0.01

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): 31, 118

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, FOXO4_01, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION, GOBP_CELLULAR_RESPONSE_TO_HYDROGEN_PEROXIDE

GO Biological Process (10): positive regulation of endothelial cell proliferation (GO:0001938), positive regulation of leukocyte chemotaxis (GO:0002690), regulation of transcription by RNA polymerase II (GO:0006357), chemotaxis (GO:0006935), inflammatory response (GO:0006954), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), positive regulation of interleukin-8 production (GO:0032757), cellular response to hydrogen peroxide (GO:0070301), positive regulation of transcription by RNA polymerase II (GO:0045944)

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 double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

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
cellular anatomical structure	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
positive regulation of leukocyte migration	1
regulation of leukocyte chemotaxis	1
leukocyte chemotaxis	1
positive regulation of chemotaxis	1
regulation of DNA-templated transcription	1
response to chemical	1
taxis	1
defense response	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
positive regulation of DNA-templated transcription	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
chromosome	1

Protein interactions and networks

STRING

344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF580	DRAP1	Q14919	349
ZNF580	CACNG3	O60359	318
ZNF580	SLC24A3	Q9HC58	311
ZNF580	WRNIP1	Q96S55	311
ZNF580	EML3	Q32P44	310
ZNF580	CAMK1G	Q96NX5	299
ZNF580	ECEL1	O95672	272
ZNF580	MT1M	Q8N339	270
ZNF580	SCGN	O76038	269
ZNF580	SSC5D	A1L4H1	262
ZNF580	CDC42EP4	Q9H3Q1	257
ZNF580	FUT7	Q11130	254
ZNF580	POU2F2	P09086	249
ZNF580	MT1F	P04733	244
ZNF580	CAPZA2	P47755	237

IntAct

71 interactions, top by confidence:

A	B	Type	Score
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
KRTAP10-7	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
KRT40	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
FSD2	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
KRT27	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
KHDRBS3	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
IKZF1	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
BANP	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
MDFI	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
KRT34	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
PSTPIP1	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
PAX9	ZNF580	psi-mi:“MI:0915”(physical association)	0.370
XBP1	ZNF580	psi-mi:“MI:0915”(physical association)	0.370
ZNF580	ARHGEF6	psi-mi:“MI:0915”(physical association)	0.370
ZNF580	SH3GL2	psi-mi:“MI:0915”(physical association)	0.370
ZNF580	TSC22D4	psi-mi:“MI:0915”(physical association)	0.370
RAD54B	ZNF580	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (32): TSC22D4 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Affinity Capture-MS), ZNF580 (Affinity Capture-MS), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid), ZNF580 (Two-hybrid)

ESM2 similar proteins: A1YGK1, A2T7E6, A8K8V0, B1WBS3, B2RXF5, C9JTQ0, O14559, O43918, O70146, O88282, P10074, Q15569, Q2QGD7, Q5FWU5, Q5R633, Q5RJR4, Q5T619, Q5XJV6, Q63572, Q6IQX8, Q6PD29, Q6XYB7, Q80VM4, Q80YF9, Q811H0, Q8BI69, Q8BXX2, Q8JZL0, Q8N143, Q8N8E2, Q8NCA9, Q8WUU4, Q90850, Q91X45, Q96C55, Q96H86, Q96Q04, Q96SL8, Q96SZ4, Q9BV97

Diamond homologs: Q96C55, Q9D0B1, Q9DB38, Q9P0T4, Q9UK33, Q5NBY9, Q9HBE1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	5	17.4×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

7 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	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1182 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55635628:GGACA:G	donor_gain	1.0000
19:55635629:GACA:G	donor_gain	1.0000
19:55635619:G:GT	donor_gain	0.9900
19:55635636:G:GG	donor_gain	0.9900
19:55641088:G:GT	donor_gain	0.9900
19:55641122:G:T	donor_gain	0.9900
19:55641180:CGGGG:C	donor_loss	0.9900
19:55641181:GGG:G	donor_gain	0.9900
19:55641181:GGGGT:G	donor_loss	0.9900
19:55641182:GG:G	donor_gain	0.9900
19:55641182:GGG:G	donor_gain	0.9900
19:55641182:GGGTA:G	donor_loss	0.9900
19:55641183:GG:G	donor_gain	0.9900
19:55641183:GGTA:G	donor_loss	0.9900
19:55641184:G:GC	donor_loss	0.9900
19:55641184:G:GG	donor_gain	0.9900
19:55641185:T:A	donor_loss	0.9900
19:55641249:G:T	donor_gain	0.9900
19:55642488:C:A	acceptor_gain	0.9900
19:55642495:A:AG	acceptor_gain	0.9900
19:55642496:G:GG	acceptor_gain	0.9900
19:55642496:GCT:G	acceptor_gain	0.9900
19:55635632:A:G	donor_gain	0.9800
19:55640125:GCT:G	acceptor_gain	0.9800
19:55641122:G:GT	donor_gain	0.9800
19:55641249:G:GT	donor_gain	0.9800
19:55642485:C:CA	acceptor_gain	0.9800
19:55642495:AGCT:A	acceptor_gain	0.9800
19:55642496:G:GA	acceptor_loss	0.9800
19:55642496:GC:G	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000112651 (19:55641738 G>A), RS1000683479 (19:55639217 C>T), RS1001512786 (19:55642941 C>A,G), RS1001617916 (19:55642640 GC>G), RS1001687946 (19:55639906 C>A,T), RS1002134977 (19:55643627 C>G,T), RS1002166312 (19:55643479 C>G,T), RS1003189444 (19:55643927 C>G,T), RS1003387430 (19:55640685 C>T), RS1003692352 (19:55643763 C>A,G), RS1003764323 (19:55640842 C>G), RS1003837469 (19:55641015 G>A), RS1004139909 (19:55641138 C>T), RS1004169592 (19:55640905 G>C,T), RS1004845792 (19:55639874 C>T)

Disease associations

OMIM: gene MIM:617888 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
diallyl trisulfide	increases expression	1
monomethylarsonous acid	decreases expression	1
ICG 001	decreases expression	1
ON 01910	affects expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Methotrexate	affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Selenium	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects 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_HD30	HEK293 eGFP-ZNF580	Transformed cell line	Female

Clinical trials (associated diseases)

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