ZNF593

Summary

ZNF593 (zinc finger protein 593, HGNC:30943) is a protein-coding gene on chromosome 1p36.11, encoding Zinc finger protein 593 (O00488). Involved in pre-60S ribosomal particles maturation by promoting the nuclear export of the 60S ribosome. It is a selective cancer dependency (DepMap: 26.8% of cell lines).

Enables preribosome binding activity and zinc ion binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm.

Source: NCBI Gene 51042 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 18 total
• Cancer dependency (DepMap): dependent in 26.8% of screened cell lines
• MANE Select transcript: NM_015871

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30943
Approved symbol	ZNF593
Name	zinc finger protein 593
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	ZT86
Ensembl gene	ENSG00000142684
Ensembl biotype	protein_coding
OMIM	616698
Entrez	51042

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000270812, ENST00000374266

RefSeq mRNA: 1 — MANE Select: NM_015871 NM_015871

CCDS: CCDS275

Canonical transcript exons

ENST00000374266 — 3 exons

Exon	Start	End
ENSE00000955850	26170418	26170480
ENSE00000955851	26170575	26170873
ENSE00001562469	26169908	26170183

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 94.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.8449 / max 460.4157, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1561	72.2132	1815
1562	1.6316	934

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	94.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.11	gold quality
muscle of leg	UBERON:0001383	93.76	gold quality
body of pancreas	UBERON:0001150	93.68	gold quality
right lobe of liver	UBERON:0001114	92.35	gold quality
mucosa of transverse colon	UBERON:0004991	91.85	gold quality
muscle organ	UBERON:0001630	91.83	gold quality
body of stomach	UBERON:0001161	91.58	gold quality
gluteal muscle	UBERON:0002000	91.29	gold quality
apex of heart	UBERON:0002098	91.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.12	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.81	gold quality
oocyte	CL:0000023	89.74	gold quality
peritoneum	UBERON:0002358	89.48	gold quality
omental fat pad	UBERON:0010414	89.48	gold quality
left adrenal gland	UBERON:0001234	89.15	gold quality
right atrium auricular region	UBERON:0006631	89.05	gold quality
left adrenal gland cortex	UBERON:0035825	88.95	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.82	gold quality
heart left ventricle	UBERON:0002084	88.72	gold quality
left uterine tube	UBERON:0001303	88.68	gold quality
pancreas	UBERON:0001264	88.58	gold quality
adenohypophysis	UBERON:0002196	88.56	gold quality
left lobe of thyroid gland	UBERON:0001120	88.55	gold quality
right adrenal gland	UBERON:0001233	88.52	gold quality
left coronary artery	UBERON:0001626	88.46	gold quality
skin of abdomen	UBERON:0001416	88.40	gold quality
lower esophagus mucosa	UBERON:0035834	88.38	gold quality
cardiac ventricle	UBERON:0002082	88.26	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-75367	no	166.68
E-HCAD-5	no	2.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting ZNF593, 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-3912-5P	99.95	66.11	925
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-6760-3P	96.35	68.31	1001

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• The tertiary structure of the zinc finger domain of ZNF593 is composed of a beta-hairpin that positions the cysteine side chains for zinc coordination, followed by an atypical kinked alpha-helix containing the two histidine side chain ligands. (PMID:18287285)
• LncRNA ZNF593-AS Alleviates Contractile Dysfunction in Dilated Cardiomyopathy. (PMID:33550812)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf593	ENSDARG00000044102
mus_musculus	Zfp593	ENSMUSG00000028840
rattus_norvegicus	Zfp593	ENSRNOG00000016392
drosophila_melanogaster	CG3224	FBGN0029885
caenorhabditis_elegans		WBGENE00013236

Paralogs (1): NDUFAB1 (ENSG00000004779)

Protein

Protein identifiers

Zinc finger protein 593 — O00488 (reviewed: O00488)

Alternative names: Zinc finger protein T86

All UniProt accessions (2): O00488, A9J4F5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-60S ribosomal particles maturation by promoting the nuclear export of the 60S ribosome. Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity.

Subunit / interactions. Associates with pre-60S ribosomal particles.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Tissue specificity. Ubiquitous. Detected in spleen, prostate, testis, small intestine, colon and to a minor level in thymus and peripheral blood leukocytes.

Domain organisation. The protein is largely disordered, with the exception of the zinc finger domain.

Similarity. Belongs to the ZNF593/BUD20 C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_056955* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR013087	Znf_C2H2_type	Domain
IPR022755	Znf_C2H2_jaz	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051879	C2H2-ZF_Maturation_Protein	Family

Pfam: PF12171

UniProt features (13 total): helix 3, turn 2, region of interest 2, compositionally biased region 2, chain 1, zinc finger region 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
8FLE	ELECTRON MICROSCOPY	2.48
8FL3	ELECTRON MICROSCOPY	2.53
8FL7	ELECTRON MICROSCOPY	2.55
8FLB	ELECTRON MICROSCOPY	2.55
8FLD	ELECTRON MICROSCOPY	2.58
8FL6	ELECTRON MICROSCOPY	2.62
8FLA	ELECTRON MICROSCOPY	2.63
8FLF	ELECTRON MICROSCOPY	2.65
8FL2	ELECTRON MICROSCOPY	2.67
8FL9	ELECTRON MICROSCOPY	2.75
8FLC	ELECTRON MICROSCOPY	2.76
8IDT	ELECTRON MICROSCOPY	2.8
8RL2	ELECTRON MICROSCOPY	2.84
8FL4	ELECTRON MICROSCOPY	2.89
8IDY	ELECTRON MICROSCOPY	3
8INF	ELECTRON MICROSCOPY	3
6LU8	ELECTRON MICROSCOPY	3.13
8INE	ELECTRON MICROSCOPY	3.2
8INK	ELECTRON MICROSCOPY	3.2
8IPD	ELECTRON MICROSCOPY	3.2
8IPY	ELECTRON MICROSCOPY	3.2
6LSS	ELECTRON MICROSCOPY	3.23
8IE3	ELECTRON MICROSCOPY	3.3
8IR3	ELECTRON MICROSCOPY	3.5
8IPX	ELECTRON MICROSCOPY	4.3
1ZR9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00488-F1	77.25	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 163 (showing top): ATF_B, CREL_01, GOBP_RIBOSOME_BIOGENESIS, PAX4_01, BASSO_B_LYMPHOCYTE_NETWORK, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, AREB6_01, BROWNE_HCMV_INFECTION_16HR_UP, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, NFKB_Q6, CREB_Q4

GO Biological Process (3): ribosome biogenesis (GO:0042254), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding (GO:1903026)

GO Molecular Function (7): DNA binding (GO:0003677), zinc ion binding (GO:0008270), preribosome binding (GO:1990275), nucleic acid binding (GO:0003676), protein binding (GO:0005515), ribonucleoprotein complex binding (GO:0043021), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
nuclear lumen	2
cellular anatomical structure	2
ribonucleoprotein complex biogenesis	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
regulation of RNA polymerase II regulatory region sequence-specific DNA binding	1
negative regulation of transcription regulatory region DNA binding	1
nucleic acid binding	1
transition metal ion binding	1
ribonucleoprotein complex binding	1
protein-containing complex binding	1
cation binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF593	ZNF622	Q969S3	483
ZNF593	GNL2	Q13823	478
ZNF593	RSL24D1	Q9UHA3	474
ZNF593	DDX27	Q96GQ7	472
ZNF593	LSG1	Q9H089	466
ZNF593	NOP16	Q9Y3C1	462
ZNF593	MRTO4	Q9UKD2	461
ZNF593	NMD3	Q96D46	456
ZNF593	CCDC9	Q9Y3X0	443
ZNF593	SUOX	P51687	433
ZNF593	DALRD3	Q5D0E6	431
ZNF593	LLPH	Q9BRT6	424
ZNF593	EIF6	P56537	424
ZNF593	PA2G4	Q9UQ80	421
ZNF593	TIMM44	O43615	419

IntAct

50 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
LNX1	ZNF593	psi-mi:“MI:0915”(physical association)	0.560
ZNF593	PICK1	psi-mi:“MI:0915”(physical association)	0.560
ZNF593	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZNF689	ZNF593	psi-mi:“MI:0914”(association)	0.530
LUC7L2	ZNF593	psi-mi:“MI:0914”(association)	0.530
CGAS	ZNF593	psi-mi:“MI:0915”(physical association)	0.400
POLR1H	ZNF593	psi-mi:“MI:0915”(physical association)	0.370
GPR3	ZNF593	psi-mi:“MI:0915”(physical association)	0.370
ZNF593	MAP3K7	psi-mi:“MI:0915”(physical association)	0.370
MAPK8IP2	ZNF593	psi-mi:“MI:0915”(physical association)	0.370
MAP3K20	ZNF593	psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLEC3A	ZNF593	psi-mi:“MI:0914”(association)	0.350
PRR20E	ZNF593	psi-mi:“MI:0914”(association)	0.350
CCDC60	ZNF593	psi-mi:“MI:0914”(association)	0.350
ARRDC3	ZNF593	psi-mi:“MI:0914”(association)	0.350
CHCHD10	ZNF593	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350

BioGRID (65): LNX1 (Two-hybrid), ZNF593 (Co-fractionation), ZNF593 (Biochemical Activity), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS), ZNF593 (Affinity Capture-MS)

ESM2 similar proteins: A2XIP9, A4IIB1, A5D7C2, A5DFT1, A5DYR5, B0BLT0, O00488, O42832, P25582, P34670, P38344, P41900, Q08004, Q09776, Q2VPG3, Q32LB0, Q3TWF6, Q4SQ06, Q4WVH3, Q54N72, Q553S1, Q5BH88, Q5EB92, Q5RJT2, Q5XIQ5, Q5ZKM1, Q6BNQ8, Q6BWR0, Q6C9Q1, Q6CV12, Q6DD06, Q6DGI3, Q6FX63, Q6GPP0, Q6NV26, Q751U1, Q75LU5, Q80UZ2, Q8SWF6, Q96NC0

Diamond homologs: B0BLT0, O00488, Q08004, Q553S1, Q8SWF6, Q9DB42, Q9P370, Q9U239, Q9W3Y0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

508 predictions. Top by Δscore:

Variant	Effect	Δscore
1:26170180:GCGC:G	donor_gain	1.0000
1:26170182:GC:G	donor_gain	1.0000
1:26170184:G:GG	donor_gain	1.0000
1:26170416:A:AG	acceptor_gain	1.0000
1:26170416:AG:A	acceptor_gain	1.0000
1:26170417:G:GG	acceptor_gain	1.0000
1:26170417:GG:G	acceptor_gain	1.0000
1:26170417:GGA:G	acceptor_gain	1.0000
1:26170481:G:GA	donor_loss	1.0000
1:26170488:GGA:G	donor_gain	1.0000
1:26170489:GAG:G	donor_gain	1.0000
1:26170573:A:AG	acceptor_gain	1.0000
1:26170574:G:GG	acceptor_gain	1.0000
1:26170574:GGCT:G	acceptor_gain	1.0000
1:26170099:G:T	donor_gain	0.9900
1:26170181:CGCG:C	donor_loss	0.9900
1:26170183:CG:C	donor_loss	0.9900
1:26170184:G:A	donor_loss	0.9900
1:26170185:TGA:T	donor_loss	0.9900
1:26170186:G:GC	donor_loss	0.9900
1:26170187:A:AC	donor_loss	0.9900
1:26170188:G:C	donor_loss	0.9900
1:26170194:G:GT	donor_gain	0.9900
1:26170262:G:GT	donor_gain	0.9900
1:26170408:A:AG	acceptor_gain	0.9900
1:26170416:AGGAG:A	acceptor_gain	0.9900
1:26170417:GGAGG:G	acceptor_gain	0.9900
1:26170481:G:GG	donor_gain	0.9900
1:26170491:G:GG	donor_gain	0.9900
1:26170573:A:AT	acceptor_loss	0.9900

AlphaMissense

855 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:26170475:G:C	K86N	0.993
1:26170475:G:T	K86N	0.993
1:26170615:G:C	A102P	0.992
1:26170452:C:G	H79D	0.991
1:26170454:C:A	H79Q	0.990
1:26170454:C:G	H79Q	0.990
1:26170470:C:G	H85D	0.989
1:26170472:C:A	H85Q	0.986
1:26170472:C:G	H85Q	0.986
1:26170170:T:C	C63R	0.985
1:26170465:A:T	K83I	0.983
1:26170452:C:A	H79N	0.982
1:26170180:G:A	C66Y	0.981
1:26170466:A:C	K83N	0.981
1:26170466:A:T	K83N	0.981
1:26170170:T:A	C63S	0.980
1:26170171:G:C	C63S	0.980
1:26170425:T:C	F70L	0.980
1:26170427:C:A	F70L	0.980
1:26170427:C:G	F70L	0.980
1:26170461:T:C	S82P	0.978
1:26170586:T:C	L92P	0.977
1:26170179:T:C	C66R	0.976
1:26170577:T:C	L89P	0.976
1:26170179:T:A	C66S	0.975
1:26170180:G:C	C66S	0.975
1:26170470:C:A	H85N	0.975
1:26170181:C:G	C66W	0.972
1:26170627:G:C	A106P	0.972
1:26170153:G:A	G57E	0.971

dbSNP variants (sampled 300 via entrez): RS1000438754 (1:26169162 A>G), RS1001791870 (1:26168450 A>G), RS1003442049 (1:26170564 C>G), RS1005264087 (1:26169280 G>A), RS1005788142 (1:26169589 C>T), RS1008137840 (1:26170992 C>T), RS1008168906 (1:26171192 C>A,G,T), RS1008744371 (1:26167920 G>A), RS1009180798 (1:26169885 C>A,G), RS1009205661 (1:26170084 A>G), RS1011629816 (1:26170538 C>T), RS1012707331 (1:26168784 T>C), RS1014021399 (1:26167970 G>C), RS1015468593 (1:26169297 C>T), RS1017017858 (1:26170521 G>A)

Disease associations

OMIM: gene MIM:616698 | 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases reaction, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Nickel	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	increases expression	2
ginger extract	decreases reaction, increases abundance, decreases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
cylindrospermopsin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Air Pollutants, Occupational	affects expression	1
Caffeine	increases phosphorylation	1
Catechin	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Flavonoids	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Oils, Volatile	decreases reaction, increases abundance, decreases expression	1
Phenobarbital	affects expression	1
Plant Extracts	increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Vitamin E	decreases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3LM	Abcam HEK293T ZNF593 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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