ZNF582

Summary

ZNF582 (zinc finger protein 582, HGNC:26421) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger protein 582 (Q96NG8). May be involved in transcriptional regulation.

The protein encoded by this gene is a zing finger protein and putative transcription factor that is highly methylated in cervical cancers. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 147948 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_001320371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26421
Approved symbol	ZNF582
Name	zinc finger protein 582
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30927
Ensembl gene	ENSG00000018869
Ensembl biotype	protein_coding
OMIM	615600
Entrez	147948

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 non_stop_decay

ENST00000301310, ENST00000586929, ENST00000587778, ENST00000589143, ENST00000589895, ENST00000593145, ENST00000932869

RefSeq mRNA: 2 — MANE Select: NM_001320371 NM_001320371, NM_144690

CCDS: CCDS33121

Canonical transcript exons

ENST00000586929 — 5 exons

Exon	Start	End
ENSE00001708509	56391744	56391832
ENSE00002480943	56390375	56390501
ENSE00002493313	56390001	56390096
ENSE00002780726	56382751	56385184
ENSE00002865128	56393220	56393534

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 88.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.8214 / max 54.2742, expressed in 1290 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182879	1.8494	1037
182880	0.9721	548

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	88.07	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.74	gold quality
ileal mucosa	UBERON:0000331	85.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.96	gold quality
upper arm skin	UBERON:0004263	80.45	gold quality
pancreatic ductal cell	CL:0002079	79.92	silver quality
apex of heart	UBERON:0002098	79.00	gold quality
right adrenal gland	UBERON:0001233	78.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.75	gold quality
cerebellar hemisphere	UBERON:0002245	77.63	gold quality
cerebellar cortex	UBERON:0002129	77.59	gold quality
right adrenal gland cortex	UBERON:0035827	77.58	gold quality
right lobe of thyroid gland	UBERON:0001119	77.52	gold quality
left lobe of thyroid gland	UBERON:0001120	77.43	gold quality
adenohypophysis	UBERON:0002196	77.26	gold quality
epithelial cell of pancreas	CL:0000083	77.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.09	gold quality
deltoid	UBERON:0001476	76.91	silver quality
left adrenal gland	UBERON:0001234	76.78	gold quality
spinal cord	UBERON:0002240	76.71	gold quality
left adrenal gland cortex	UBERON:0035825	76.68	gold quality
pituitary gland	UBERON:0000007	76.64	gold quality
islet of Langerhans	UBERON:0000006	76.61	gold quality
thyroid gland	UBERON:0002046	76.55	gold quality
cerebellum	UBERON:0002037	76.46	gold quality
putamen	UBERON:0001874	76.43	gold quality
nucleus accumbens	UBERON:0001882	76.20	gold quality
adrenal cortex	UBERON:0001235	76.13	gold quality
oocyte	CL:0000023	75.96	gold quality
caudate nucleus	UBERON:0001873	75.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.94

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1983.1	ZNF582	More than 3 adjacent zinc fingers
MA1983.2	ZNF582	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:31162603

miRNA regulators (miRDB)

72 targeting ZNF582, 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-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-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4677-5P	99.70	70.09	1940

Literature-anchored findings (GeneRIF, showing 16)

• ZNF582 is frequently methylated in cervical intraepithelial neoplasia 3 and worse lesions (PMID:22815913)
• Methylation levels of ZNF582 in uterine cervix adenocarcinomas is significantly higher than those in normal cervical tissues. (PMID:24407576)
• This is the first study to show that ZNF582 methylation analysis of cervical swabs may be a promising choice in the positive triage of cytological diagnoses of low-grade squamous intraepithelial lesions (PMID:25134998)
• Results show that promoter hypermethylation of ADCY8, CDH8, and ZNF582 are correlated with high-grade squamous intraepithelial lesion. (PMID:27651839)
• conclude that hypermethylated ZNF582 and PAX1 are effective biomarkers for the detection of oral dysplasia and oral cancer and for the prediction of oral cancer recurrence (PMID:27865370)
• DNA methylation status of ZNF582 showed a relatively good sensitivity and specificity for the detection of ESOPHAGEAL SQUAMOUS CELL CARCINOMA. (PMID:28241446)
• Hypermethylated ZNF582 and PAX1 genes in oral epithelial cells collected by mouth rinse are effective biomarkers for the detection of oral dysplasia and oral cancer. (PMID:28960639)
• Hypermethylated ZNF582 and PAX1 genes in the oral scrapings collected from adjacent normal oral mucosal sites rather than cancer sites are associated with aggressive progression and poor prognosis of OSCC (PMID:29224816)
• ZNF582 methylation has a prospect to be an auxiliary biomarker for cervical cancer (Meta-Analysis) (PMID:30732145)
• The methylation levels ofPAX1, SOX1 and ZNF582 genes were all higher in cancer tissues. (PMID:31629253)
• Hypermethylated PAX1 and ZNF582 genes in the tissue sample are associated with aggressive progression of oral squamous cell carcinoma. (PMID:32428271)
• The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer. (PMID:32514824)
• ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin-3 and NRXN3. (PMID:33038291)
• ZNF582 promoter methylation predicts cervical cancer radiosensitivity and ZNF582 protein overexpression reduces radiosensitivity by cell cycle arrest in S phase. (PMID:35642528)
• ZNF582 overexpression restrains the progression of clear cell renal cell carcinoma by enhancing the binding of TJP2 and ERK2 and inhibiting ERK2 phosphorylation. (PMID:36966163)
• Relationship between p16/ki67 immunoscores and PAX1/ZNF582 methylation status in precancerous and cancerous cervical lesions in high-risk HPV-positive women. (PMID:39304838)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp582	ENSMUSG00000109398
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF264 (ENSG00000083844), ZNF343 (ENSG00000088876), ZNF684 (ENSG00000117010), ZNF133 (ENSG00000125846), ZNF557 (ENSG00000130544), ZNF337 (ENSG00000130684), ZNF20 (ENSG00000132010), ZFP37 (ENSG00000136866), ZNF614 (ENSG00000142556), KRBOX4 (ENSG00000147121), ZNF599 (ENSG00000153896), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF558 (ENSG00000167785), ZNF35 (ENSG00000169981), ZNF778 (ENSG00000170100), ZNF439 (ENSG00000171291), ZNF440 (ENSG00000171295), ZNF556 (ENSG00000172000), ZNF554 (ENSG00000172006), ZNF596 (ENSG00000172748), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF404 (ENSG00000176222), ZNF491 (ENSG00000177599), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF875 (ENSG00000181666), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300), ZNF70 (ENSG00000187792)

Protein

Protein identifiers

Zinc finger protein 582 — Q96NG8 (reviewed: Q96NG8)

All UniProt accessions (5): A0A075B771, A0A075B772, Q96NG8, K7EKI7, K7ESE7

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 (2): NP_001307300, NP_653291 (=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

UniProt features (21 total): zinc finger region 10, sequence conflict 6, sequence variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NG8-F1	63.04	0.05

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 44 (showing top): TCF11_01, NOUZOVA_METHYLATED_IN_APL, STAT1_02, YKACATTT_UNKNOWN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, STAT1_03, FIGUEROA_AML_METHYLATION_CLUSTER_1_UP, FIGUEROA_AML_METHYLATION_CLUSTER_2_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, FIGUEROA_AML_METHYLATION_CLUSTER_4_UP, FIGUEROA_AML_METHYLATION_CLUSTER_6_UP, FIGUEROA_AML_METHYLATION_CLUSTER_7_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, IRF5_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 (6): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), 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
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
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF582	PAX1	P15863	776
ZNF582	TAFA4	Q96LR4	579
ZNF582	SOX1	O00570	577
ZNF582	WDR17	Q8IZU2	542
ZNF582	PTPRR	Q15256	479
ZNF582	RUBCNL	Q9H714	479
ZNF582	LHX8	Q68G74	474
ZNF582	EPB41L3	Q9Y2J2	474
ZNF582	ST6GALNAC5	Q9BVH7	418
ZNF582	POU4F3	Q15319	403
ZNF582	LMX1A	Q8TE12	382
ZNF582	PCDHA13	Q9Y5I0	373
ZNF582	CDH8	P55286	371
ZNF582	PCDHA4	Q9UN74	364
ZNF582	NKX6-1	P78426	353

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ZNF582	NECTIN4	psi-mi:“MI:0915”(physical association)	0.590
ZNF582	ECE1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (6): PVRL4 (Affinity Capture-MS), PVRL4 (Affinity Capture-MS), ZNF582 (Proximity Label-MS), ZNF582 (Affinity Capture-MS), PVRL4 (Affinity Capture-MS), ZNF582 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PQL4, A0JPL0, A2RRD8, A6NHJ4, A6NP11, B4DX44, O75346, O95780, P0CB33, P21506, P51508, P52738, Q0D2J5, Q0VGE8, Q12901, Q13360, Q14593, Q15973, Q2M218, Q2M3X9, Q2VY69, Q3SXZ3, Q5HY98, Q5RCJ2, Q5VIY5, Q6J6I6, Q7L2R6, Q86XU0, Q86Y25, Q8IW36, Q8IYN0, Q8IYX0, Q8N782, Q8N883, Q8N9Z0, Q8NDP4, Q95K49, Q969W8, Q96H40, Q96N58

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

566 predictions. Top by Δscore:

Variant	Effect	Δscore
19:56391742:A:AC	donor_gain	1.0000
19:56391743:C:CC	donor_gain	1.0000
19:56391833:C:CC	acceptor_gain	1.0000
19:56385185:C:CC	acceptor_gain	0.9900
19:56389757:T:A	donor_gain	0.9900
19:56389997:TCACC:T	donor_loss	0.9900
19:56389998:CACCT:C	donor_loss	0.9900
19:56389999:ACCT:A	donor_loss	0.9900
19:56390000:C:A	donor_loss	0.9900
19:56390499:CCC:C	acceptor_gain	0.9900
19:56390500:CCC:C	acceptor_gain	0.9900
19:56391743:CA:C	donor_gain	0.9900
19:56391784:T:TA	donor_gain	0.9900
19:56391828:TAGAG:T	acceptor_gain	0.9900
19:56391830:GAG:G	acceptor_gain	0.9900
19:56391830:GAGC:G	acceptor_loss	0.9900
19:56391832:GC:G	acceptor_loss	0.9900
19:56391833:C:CA	acceptor_loss	0.9900
19:56382920:T:C	acceptor_gain	0.9800
19:56382924:A:C	acceptor_gain	0.9800
19:56385180:CAATA:C	acceptor_gain	0.9800
19:56389784:A:AC	donor_gain	0.9800
19:56389995:ACTC:A	donor_loss	0.9800
19:56390094:GACCT:G	acceptor_loss	0.9800
19:56390097:C:CA	acceptor_loss	0.9800
19:56390368:ACCTT:A	donor_loss	0.9800
19:56390369:CCTTA:C	donor_loss	0.9800
19:56390370:CTTA:C	donor_loss	0.9800
19:56390371:TTA:T	donor_loss	0.9800
19:56390372:TA:T	donor_loss	0.9800

AlphaMissense

3458 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:56384541:G:C	F292L	0.997
19:56384541:G:T	F292L	0.997
19:56384543:A:G	F292L	0.997
19:56384625:A:C	F264L	0.997
19:56384625:A:T	F264L	0.997
19:56384627:A:G	F264L	0.997
19:56384205:G:C	F404L	0.995
19:56384205:G:T	F404L	0.995
19:56384207:A:G	F404L	0.995
19:56384289:A:C	F376L	0.995
19:56384289:A:T	F376L	0.995
19:56384291:A:G	F376L	0.995
19:56384709:G:C	F236L	0.995
19:56384709:G:T	F236L	0.995
19:56384711:A:G	F236L	0.995
19:56384121:A:C	F432L	0.994
19:56384121:A:T	F432L	0.994
19:56384123:A:G	F432L	0.994
19:56384373:A:C	F348L	0.994
19:56384373:A:T	F348L	0.994
19:56384375:A:G	F348L	0.994
19:56384536:C:G	R294P	0.994
19:56384457:A:C	F320L	0.993
19:56384457:A:T	F320L	0.993
19:56384459:A:G	F320L	0.993
19:56384593:C:G	R275P	0.993
19:56384272:A:G	L382P	0.992
19:56384524:A:G	L298P	0.991
19:56384188:A:G	L410P	0.989
19:56384260:T:G	Q386P	0.987

dbSNP variants (sampled 300 via entrez): RS1000186745 (19:56384447 A>G), RS1000225683 (19:56393738 C>A,G,T), RS1000273150 (19:56386851 A>G), RS1000411706 (19:56391685 A>T), RS1001053163 (19:56388958 A>G), RS1001368561 (19:56385171 T>A,C), RS1002334362 (19:56395154 A>G), RS1002378318 (19:56383578 T>C), RS1002686893 (19:56394864 T>G), RS1003058808 (19:56387034 T>C), RS1003288289 (19:56390210 G>A), RS1003426010 (19:56384343 CTGA>C), RS1004218120 (19:56383460 C>T), RS1004236074 (19:56387465 C>T), RS1004358072 (19:56389377 G>A)

Disease associations

OMIM: gene MIM:615600 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009269_20	Dental caries (decayed and filled deciduous teeth)	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
hydroxyhydroquinone	increases expression	1
arsenite	decreases expression, increases methylation	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	decreases methylation, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Irinotecan	affects cotreatment, increases response to substance	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Leucovorin	affects cotreatment, increases response to substance	1
Fluorouracil	increases response to substance, affects cotreatment	1
Valproic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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