ZNF584

Summary

ZNF584 (zinc finger protein 584, HGNC:27318) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger protein 584 (Q8IVC4). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 201514 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_173548

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27318
Approved symbol	ZNF584
Name	zinc finger protein 584
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	FLJ39899
Ensembl gene	ENSG00000171574
Ensembl biotype	protein_coding
Entrez	201514

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000306910, ENST00000322834, ENST00000593920, ENST00000594993, ENST00000596281, ENST00000596921, ENST00000598901, ENST00000599145, ENST00000599238, ENST00000703727, ENST00000703728, ENST00000703729

RefSeq mRNA: 3 — MANE Select: NM_173548 NM_001318002, NM_001363680, NM_173548

CCDS: CCDS12979, CCDS82414, CCDS86814

Canonical transcript exons

ENST00000306910 — 4 exons

Exon	Start	End
ENSE00001169792	58409941	58410091
ENSE00003119974	58408649	58409165
ENSE00003547209	58415524	58415646
ENSE00003574851	58416811	58418327

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 84.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1079 / max 81.2498, expressed in 1673 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177844	3.0584	1454
177845	1.9059	1193
177843	1.1436	526

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	84.81	gold quality
secondary oocyte	CL:0000655	83.11	gold quality
stromal cell of endometrium	CL:0002255	80.84	gold quality
gastrocnemius	UBERON:0001388	80.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.07	gold quality
cortical plate	UBERON:0005343	79.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.66	gold quality
tendon of biceps brachii	UBERON:0008188	79.60	gold quality
muscle of leg	UBERON:0001383	79.52	gold quality
right atrium auricular region	UBERON:0006631	79.28	gold quality
heart left ventricle	UBERON:0002084	79.25	gold quality
cardiac ventricle	UBERON:0002082	78.96	gold quality
prefrontal cortex	UBERON:0000451	78.86	gold quality
right adrenal gland cortex	UBERON:0035827	78.76	gold quality
ventricular zone	UBERON:0003053	78.75	gold quality
cardiac atrium	UBERON:0002081	78.71	gold quality
left adrenal gland cortex	UBERON:0035825	78.24	gold quality
right uterine tube	UBERON:0001302	78.21	gold quality
heart	UBERON:0000948	78.18	gold quality
islet of Langerhans	UBERON:0000006	78.10	gold quality
left adrenal gland	UBERON:0001234	78.02	gold quality
right adrenal gland	UBERON:0001233	77.94	gold quality
skin of abdomen	UBERON:0001416	77.88	gold quality
skin of leg	UBERON:0001511	77.70	gold quality
upper arm skin	UBERON:0004263	77.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.54	gold quality
lower esophagus	UBERON:0013473	77.51	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.48	gold quality
adrenal cortex	UBERON:0001235	77.43	gold quality
descending thoracic aorta	UBERON:0002345	77.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting ZNF584, 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-1299	99.77	71.24	2389
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-4433A-5P	96.79	65.01	599
HSA-MIR-3165	96.18	66.22	473
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-6735-3P	96.10	63.81	600
HSA-MIR-3675-5P	95.90	65.80	474
HSA-MIR-659-5P	95.36	65.00	300
HSA-MIR-6890-5P	92.89	65.83	442

Literature-anchored findings (GeneRIF, showing 1)

• total of 1799 differentially methylated regions were identified including SLC6A3, Rab40C, ZNF584, and FOXD3 whose significant methylation differences were confirmed in breast cancer patients through quantitative real-time polymerase chain reaction.Methylation of those aforementioned genes in white blood cells of our young patients may highlight their potential as early epimarkers (PMID:28349825)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfx	ENSDARG00000074453
danio_rerio		ENSDARG00000098424
mus_musculus	Zfy2	ENSMUSG00000000103
mus_musculus	Zfy1	ENSMUSG00000053211
rattus_norvegicus	Zfy1	ENSRNOG00000053042

Paralogs (38): ZFX (ENSG00000005889), ZBTB11 (ENSG00000066422), ZFAT (ENSG00000066827), ZFY (ENSG00000067646), ZNF586 (ENSG00000083828), IKZF5 (ENSG00000095574), ZNF419 (ENSG00000105136), ZNF549 (ENSG00000121406), ZSCAN20 (ENSG00000121903), ZNF304 (ENSG00000131845), PRDM15 (ENSG00000141956), ZNF660 (ENSG00000144792), ZNF711 (ENSG00000147180), ZNF773 (ENSG00000152439), ZNF256 (ENSG00000152454), ZNF837 (ENSG00000152475), ZNF691 (ENSG00000164011), ZNF610 (ENSG00000167554), E4F1 (ENSG00000167967), ZNF562 (ENSG00000171466), ZNF561 (ENSG00000171469), ZIK1 (ENSG00000171649), ZNF570 (ENSG00000171827), ZSCAN2 (ENSG00000176371), ZNF552 (ENSG00000178935), ZNF154 (ENSG00000179909), ZNF792 (ENSG00000180884), ZNF793 (ENSG00000188227), ZNF548 (ENSG00000188785), ZNF79 (ENSG00000196152), ZNF418 (ENSG00000196724), ZNF772 (ENSG00000197128), ZNF583 (ENSG00000198440), ZNF480 (ENSG00000198464), ZNF551 (ENSG00000204519), ZNF134 (ENSG00000213762), ZNF587B (ENSG00000269343), ZNF8 (ENSG00000278129)

Protein

Protein identifiers

Zinc finger protein 584 — Q8IVC4 (reviewed: Q8IVC4)

All UniProt accessions (6): Q8IVC4, F6W0P0, M0QZA3, M0R0A3, M0R2W6, M0R3F5

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 (3): NP_001304931, NP_001350609, NP_775819* (*=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

Pfam: PF00096, PF01352, PF13894

UniProt features (16 total): zinc finger region 8, region of interest 2, compositionally biased region 2, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVC4-F1	65.17	0.05

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 75 (showing top): ROVERSI_GLIOMA_COPY_NUMBER_UP, DOUGLAS_BMI1_TARGETS_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ATF6_TARGET_GENES, BARX1_TARGET_GENES, CEBPZ_TARGET_GENES, CIITA_TARGET_GENES, E2F2_TARGET_GENES, FOXJ2_TARGET_GENES, HOXB4_TARGET_GENES, HOXB6_TARGET_GENES, ID2_TARGET_GENES, NAB2_TARGET_GENES, SUPT16H_TARGET_GENES

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

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), DNA binding (GO:0003677), metal ion binding (GO:0046872)

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

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	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	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
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF584	RNF225	M0QZC1	645
ZNF584	SLC27A5	Q9Y2P5	568
ZNF584	FBXL17	Q9UF56	501
ZNF584	GNB5	O14775	482
ZNF584	EXOC4	Q96A65	481
ZNF584	LRRC61	Q9BV99	479
ZNF584	MAP10	Q9P2G4	479
ZNF584	FUT8	Q9BYC5	475
ZNF584	TSNARE1	Q96NA8	449
ZNF584	PDE4D	Q08499	448
ZNF584	REEP3	Q6NUK4	438
ZNF584	SGCZ	Q96LD1	438
ZNF584	SLC18B1	Q6NT16	433
ZNF584	CLCC1	Q96S66	430
ZNF584	NRXN1	Q9ULB1	426

IntAct

5 interactions, top by confidence:

A	B	Type	Score
LZTR1	ZNF584	psi-mi:“MI:0915”(physical association)	0.370
ZNF584	LRP4	psi-mi:“MI:0914”(association)	0.350
APP	ZNF584	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): ZNF584 (Synthetic Lethality), ZNF584 (Affinity Capture-RNA), RNF41 (Affinity Capture-MS), MPP1 (Affinity Capture-MS), LRP4 (Affinity Capture-MS), CBX5 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), SORL1 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), ZNF584 (Affinity Capture-MS), ZNF584 (Two-hybrid), ZNF584 (Affinity Capture-RNA), ZNF584 (Two-hybrid)

ESM2 similar proteins: A0JPL0, A1L1L7, A3KN32, A3KN36, D3ZVT0, O43296, P08042, P16373, P17023, P17031, P52738, P85977, Q02975, Q12901, Q14592, Q29RZ4, Q3KNS6, Q4R6J4, Q4V8A8, Q571J5, Q5CZA5, Q5JNZ3, Q5R7I8, Q5RB33, Q5RBY9, Q5T5D7, Q61751, Q61967, Q62396, Q6GQR8, Q6ZNG0, Q6ZS27, Q7Z398, Q8BI99, Q8BIQ3, Q8IVC4, Q8IZ26, Q8N988, Q8N9Z0, Q8NDP4

Diamond homologs: A0JPL0, A2VDP4, A3KN32, A6NFI3, A6NM28, A6QLU5, B2RXC5, B4DU55, O43296, O60765, O75290, O75467, P10072, P15622, P17014, P17023, P17030, P17031, P17032, P17098, P21506, P51508, P51523, P52736, P52738, Q02975, Q06730, Q06732, Q14590, Q14929, Q16587, Q29RZ4, Q2TL60, Q3KNS6, Q3KQV3, Q49AA0, Q4R8H9, Q4V8A8, Q4V8E9, Q5FWF6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1035 predictions. Top by Δscore:

Variant	Effect	Δscore
19:58416809:AGAT:A	acceptor_gain	1.0000
19:58416810:GATG:G	acceptor_gain	1.0000
19:58408693:G:GT	donor_gain	0.9900
19:58410088:CTGGG:C	donor_loss	0.9900
19:58410089:TGGG:T	donor_loss	0.9900
19:58410090:GG:G	donor_gain	0.9900
19:58410090:GGGTA:G	donor_loss	0.9900
19:58410091:GG:G	donor_gain	0.9900
19:58410091:GGTAA:G	donor_loss	0.9900
19:58410092:GTA:G	donor_loss	0.9900
19:58410093:TAAGT:T	donor_loss	0.9900
19:58415631:A:T	donor_gain	0.9900
19:58415644:TTGGT:T	donor_loss	0.9900
19:58415645:TGG:T	donor_loss	0.9900
19:58415646:GGT:G	donor_loss	0.9900
19:58415647:G:C	donor_loss	0.9900
19:58415647:G:GG	donor_gain	0.9900
19:58415648:TAA:T	donor_loss	0.9900
19:58416806:TTCA:T	acceptor_loss	0.9900
19:58416807:TCAG:T	acceptor_loss	0.9900
19:58416808:CAGA:C	acceptor_loss	0.9900
19:58416809:A:C	acceptor_loss	0.9900
19:58409164:AGG:A	donor_loss	0.9800
19:58409165:GGT:G	donor_loss	0.9800
19:58409167:T:A	donor_loss	0.9800
19:58410088:CTGG:C	donor_gain	0.9800
19:58410092:G:GG	donor_gain	0.9800
19:58410094:AA:A	donor_loss	0.9800
19:58415519:CGCAG:C	acceptor_loss	0.9800
19:58415520:GCAGG:G	acceptor_loss	0.9800

AlphaMissense

2798 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:58417269:T:C	F251L	0.998
19:58417271:C:A	F251L	0.998
19:58417271:C:G	F251L	0.998
19:58417353:T:C	F279L	0.998
19:58417355:C:A	F279L	0.998
19:58417355:C:G	F279L	0.998
19:58417605:T:C	F363L	0.998
19:58417607:C:A	F363L	0.998
19:58417607:C:G	F363L	0.998
19:58417185:T:C	F223L	0.997
19:58417187:C:A	F223L	0.997
19:58417187:C:G	F223L	0.997
19:58417689:T:C	F391L	0.996
19:58417691:C:A	F391L	0.996
19:58417691:C:G	F391L	0.996
19:58417276:G:C	R253P	0.995
19:58417296:C:G	H260D	0.994
19:58417300:A:C	Q261P	0.994
19:58417464:C:G	H316D	0.994
19:58417550:C:A	H344Q	0.994
19:58417550:C:G	H344Q	0.994
19:58417214:C:A	H232Q	0.993
19:58417214:C:G	H232Q	0.993
19:58417296:C:A	H260N	0.993
19:58417298:C:A	H260Q	0.993
19:58417298:C:G	H260Q	0.993
19:58417464:C:A	H316N	0.993
19:58417540:T:C	L341P	0.993
19:58417562:C:A	H348Q	0.993
19:58417562:C:G	H348Q	0.993

dbSNP variants (sampled 300 via entrez): RS1000105963 (19:58401277 G>A,T), RS1000128585 (19:58418548 C>T), RS1000200275 (19:58401982 T>G), RS1000334326 (19:58404679 C>T), RS1000548299 (19:58414293 T>C,G), RS1000639841 (19:58410423 CTG>C), RS1000672793 (19:58404829 A>C), RS1000672879 (19:58406060 A>G), RS1000699732 (19:58409240 G>A), RS1000906462 (19:58411018 C>T), RS1001109400 (19:58408330 G>C), RS1001207276 (19:58411223 T>C), RS1001262655 (19:58411621 T>A), RS1001425981 (19:58406531 G>A,T), RS1001537580 (19:58414647 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004058_2	Uric acid clearance	1.000000e-06
GCST90002402_577	Platelet count	1.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HA04	K562 eGFP-ZNF584	Cancer cell line	Female

Clinical trials (associated diseases)

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