ZNF500

Summary

ZNF500 (zinc finger protein 500, HGNC:23716) is a protein-coding gene on chromosome 16p13.3, encoding Zinc finger protein 500 (O60304). 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 located in nucleus.

Source: NCBI Gene 26048 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 143 total
• MANE Select transcript: NM_021646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23716
Approved symbol	ZNF500
Name	zinc finger protein 500
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ZKSCAN18, KIAA0557, ZSCAN50
Ensembl gene	ENSG00000103199
Ensembl biotype	protein_coding
Entrez	26048

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000219478, ENST00000545009, ENST00000585977, ENST00000588602, ENST00000588942, ENST00000589422, ENST00000591026, ENST00000592425, ENST00000859887

RefSeq mRNA: 2 — MANE Select: NM_021646 NM_001303450, NM_021646

CCDS: CCDS32383, CCDS76814

Canonical transcript exons

ENST00000219478 — 6 exons

Exon	Start	End
ENSE00000667528	4762573	4762756
ENSE00001145424	4765565	4766076
ENSE00001490563	4767017	4767162
ENSE00002903692	4748239	4753058
ENSE00003533326	4760492	4760588
ENSE00003597673	4762271	4762335

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 85.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7245 / max 54.2742, expressed in 1670 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156116	4.7245	1670

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	85.22	gold quality
endometrium epithelium	UBERON:0004811	83.73	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	83.37	gold quality
nipple	UBERON:0002030	82.84	gold quality
cortical plate	UBERON:0005343	81.98	gold quality
ventricular zone	UBERON:0003053	81.60	gold quality
endocervix	UBERON:0000458	81.57	gold quality
left ovary	UBERON:0002119	81.46	gold quality
right ovary	UBERON:0002118	81.20	gold quality
paraflocculus	UBERON:0005351	81.19	gold quality
popliteal artery	UBERON:0002250	81.03	gold quality
tibial artery	UBERON:0007610	81.02	gold quality
body of uterus	UBERON:0009853	80.94	gold quality
frontal pole	UBERON:0002795	80.53	gold quality
pancreatic ductal cell	CL:0002079	80.50	silver quality
stromal cell of endometrium	CL:0002255	80.21	gold quality
oocyte	CL:0000023	80.15	gold quality
apex of heart	UBERON:0002098	80.04	gold quality
middle frontal gyrus	UBERON:0002702	79.86	silver quality
aorta	UBERON:0000947	79.78	gold quality
ganglionic eminence	UBERON:0004023	79.67	gold quality
granulocyte	CL:0000094	79.66	gold quality
sural nerve	UBERON:0015488	79.62	gold quality
ectocervix	UBERON:0012249	79.50	gold quality
right coronary artery	UBERON:0001625	79.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	79.28	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.26	gold quality
lower esophagus	UBERON:0013473	79.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.08	gold quality
ovary	UBERON:0000992	79.00	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	55.17
E-CURD-11	no	82.27
E-ANND-3	no	4.77

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2585.1	ZNF500	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

miRNA regulators (miRDB)

116 targeting ZNF500, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1273H-5P	99.77	66.32	2471

Literature-anchored findings (GeneRIF, showing 1)

• ZNF500 abolishes breast cancer proliferation and sensitizes chemotherapy by stabilizing P53 via competing with MDM2. (PMID:37700392)

Cross-species orthologs

0 orthologs

Paralogs (30): ZNF263 (ENSG00000006194), ZNF213 (ENSG00000085644), ZKSCAN1 (ENSG00000106261), ZNF205 (ENSG00000122386), ZSCAN9 (ENSG00000137185), PGBD1 (ENSG00000137338), ZNF215 (ENSG00000149054), ZSCAN12 (ENSG00000158691), ZNF394 (ENSG00000160908), ZNF75A (ENSG00000162086), ZSCAN21 (ENSG00000166529), ZNF232 (ENSG00000167840), ZNF24 (ENSG00000172466), ZNF449 (ENSG00000173275), ZSCAN4 (ENSG00000180532), ZSCAN22 (ENSG00000182318), ZNF75D (ENSG00000186376), ZNF396 (ENSG00000186496), ZNF397 (ENSG00000186812), ZSCAN30 (ENSG00000186814), ZKSCAN4 (ENSG00000187626), ZSCAN23 (ENSG00000187987), ZKSCAN3 (ENSG00000189298), ZSCAN16 (ENSG00000196812), ZSCAN25 (ENSG00000197037), ZSCAN26 (ENSG00000197062), ZNF165 (ENSG00000197279), ZKSCAN8 (ENSG00000198315), ZSCAN31 (ENSG00000235109), ZNF853 (ENSG00000236609)

Protein

Protein identifiers

Zinc finger protein 500 — O60304 (reviewed: O60304)

Alternative names: Zinc finger protein with KRAB and SCAN domains 18

All UniProt accessions (6): O60304, K7EIH1, K7EJ94, K7EM64, K7EPZ1, K7ERS9

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.

Isoforms (2)

UniProt ID	Names	Canonical?
O60304-1	1	yes
O60304-2	2

RefSeq proteins (2): NP_001290379, NP_067678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR003309	SCAN_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR038269	SCAN_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF01352, PF02023

UniProt features (13 total): zinc finger region 5, region of interest 4, domain 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60304-F1	61.14	0.19

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 98 (showing top): MORF_RAGE, MORF_FLT1, MORF_MSH3, MORF_BRCA1, MORF_ATRX, MORF_ESR1, MORF_PPP5C, MORF_FANCG, MORF_RAP1A, MORF_MT4, MORF_PRKACA, MORF_PTEN, MORF_HEAB, MORF_PAX7, MORF_TNFRSF25

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 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), 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
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
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF500	EML5	Q05BV3	526
ZNF500	TOP3B	O95985	494
ZNF500	FKBP9	O95302	475
ZNF500	CRTC3	Q6UUV7	449
ZNF500	TBCCD1	Q9NVR7	445
ZNF500	ELAVL2	Q12926	426
ZNF500	GFOD2	Q3B7J2	426
ZNF500	FBXL20	Q96IG2	424
ZNF500	RGS7	P49802	418
ZNF500	PDE4D	Q08499	418
ZNF500	SLC6A11	P48066	415
ZNF500	DUSP19	Q8WTR2	410
ZNF500	NOL9	Q5SY16	404
ZNF500	ANKS3	Q6ZW76	400
ZNF500	BCKDHB	P21953	379
ZNF500	GINS1	Q14691	379

IntAct

33 interactions, top by confidence:

A	B	Type	Score
PHF1	ZNF500	psi-mi:“MI:0915”(physical association)	0.560
ZNF500	FARS2	psi-mi:“MI:0915”(physical association)	0.560
ZNF500	HEXIM2	psi-mi:“MI:0915”(physical association)	0.560
ZNF500	GFAP	psi-mi:“MI:0915”(physical association)	0.560
ZNF500	HTRA2	psi-mi:“MI:0915”(physical association)	0.560
ZNF500	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ZNF500	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
ZNF500	HTT	psi-mi:“MI:0915”(physical association)	0.560
ZNF397	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZKSCAN8	ZNF320	psi-mi:“MI:0914”(association)	0.350
ZNF174	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TGIF2	ZNF213	psi-mi:“MI:0914”(association)	0.350
HEXIM2	ZNF500	psi-mi:“MI:0915”(physical association)	0.000
FARS2	ZNF500	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): ZNF500 (Affinity Capture-MS), ZNF500 (Affinity Capture-MS), PHF1 (Two-hybrid), FARS2 (Two-hybrid), HEXIM2 (Two-hybrid), ZNF500 (Affinity Capture-MS), ZNF500 (Affinity Capture-MS), ZNF500 (Affinity Capture-MS), ZNF500 (Positive Genetic), ZNF500 (Affinity Capture-RNA), ZNF500 (Affinity Capture-MS)

ESM2 similar proteins: A1YGK1, A2T7E6, A4D1S0, A9YTQ3, B1WBS3, I7HJS4, O43593, O43918, O60304, O75593, O95201, P0C6A0, P0C7X2, P97609, Q2MHN3, Q3B7M4, Q3SY56, Q3U133, Q58DK7, Q5JPB2, Q5SXI5, Q5T619, Q61645, Q6KAU7, Q6NUN9, Q6ZMS7, Q76NI1, Q7Z6P3, Q8BZ34, Q8BZW2, Q8CGW9, Q8IWN7, Q8IXT2, Q8IZ20, Q8NBB4, Q8NDX1, Q8NHY3, Q91X45, Q96PX9, Q99558

Diamond homologs: A1YEP8, A1YEQ3, A1YEV9, A1YFW2, A1YFW6, A1YG26, A1YG48, A1YG60, A1YGJ4, A1YGK6, A2T6E3, A2T6V8, A2T6W2, A2T712, A2T736, A2T7D2, A2T7D7, A2T7F2, A2T7F4, A2T7L7, A2T812, A6QNZ0, A6QPT6, B2KFW1, O14709, O14771, O14978, O15535, O43309, O60304, O95125, P10073, P17022, P17028, P17029, P17040, P28698, P49910, P51815, P59923

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	130
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1376 predictions. Top by Δscore:

Variant	Effect	Δscore
16:4765559:ACTC:A	donor_loss	1.0000
16:4765560:CT:C	donor_loss	1.0000
16:4765561:T:TC	donor_loss	1.0000
16:4765562:CACCC:C	donor_loss	1.0000
16:4765564:C:A	donor_loss	1.0000
16:4765564:CCCG:C	donor_gain	1.0000
16:4765579:T:TA	donor_gain	1.0000
16:4767015:A:AC	donor_gain	1.0000
16:4767016:C:CC	donor_gain	1.0000
16:4760487:GTTA:G	donor_loss	0.9900
16:4760488:TTA:T	donor_loss	0.9900
16:4760489:TA:T	donor_loss	0.9900
16:4760491:C:A	donor_loss	0.9900
16:4762266:CTCA:C	donor_loss	0.9900
16:4762267:TCA:T	donor_loss	0.9900
16:4762268:CA:C	donor_loss	0.9900
16:4762269:A:T	donor_loss	0.9900
16:4762270:C:T	donor_loss	0.9900
16:4762334:GC:G	acceptor_gain	0.9900
16:4762334:GCCTG:G	acceptor_loss	0.9900
16:4762335:CC:C	acceptor_gain	0.9900
16:4762336:C:CC	acceptor_gain	0.9900
16:4762336:CTGGG:C	acceptor_loss	0.9900
16:4765558:CACT:C	donor_loss	0.9900
16:4765563:A:AC	donor_gain	0.9900
16:4765563:AC:A	donor_gain	0.9900
16:4765564:C:CC	donor_gain	0.9900
16:4765564:CC:C	donor_gain	0.9900
16:4766075:CC:C	acceptor_gain	0.9900
16:4766076:CC:C	acceptor_gain	0.9900

AlphaMissense

3102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:4752817:G:C	F334L	1.000
16:4752817:G:T	F334L	1.000
16:4752819:A:G	F334L	1.000
16:4752481:G:C	F446L	0.999
16:4752481:G:T	F446L	0.999
16:4752483:A:G	F446L	0.999
16:4752565:G:C	F418L	0.999
16:4752565:G:T	F418L	0.999
16:4752566:A:G	F418S	0.999
16:4752567:A:G	F418L	0.999
16:4752649:G:C	F390L	0.999
16:4752649:G:T	F390L	0.999
16:4752651:A:G	F390L	0.999
16:4752733:A:C	F362L	0.999
16:4752733:A:T	F362L	0.999
16:4752735:A:G	F362L	0.999
16:4752482:A:G	F446S	0.998
16:4752526:G:C	H431Q	0.998
16:4752526:G:T	H431Q	0.998
16:4752540:G:C	H427D	0.998
16:4752624:G:C	H399D	0.998
16:4752650:A:G	F390S	0.998
16:4752734:A:G	F362S	0.998
16:4752818:A:G	F334S	0.998
16:4752538:G:C	H427Q	0.997
16:4752538:G:T	H427Q	0.997
16:4752624:G:T	H399N	0.997
16:4752778:G:C	H347Q	0.997
16:4752778:G:T	H347Q	0.997
16:4752785:C:G	R345P	0.997

dbSNP variants (sampled 300 via entrez): RS1000187045 (16:4755800 T>C), RS1000218095 (16:4756054 T>C), RS1000259365 (16:4761950 G>A), RS1000328107 (16:4751474 C>G), RS1000401287 (16:4757988 G>A,T), RS1000411131 (16:4758208 T>C,G), RS1000451619 (16:4766813 C>G), RS1000550637 (16:4754904 T>C), RS1000581697 (16:4755103 C>G), RS1000780291 (16:4750573 C>T), RS1000850672 (16:4751614 G>A), RS1000907822 (16:4767447 G>C,T), RS1000911844 (16:4763330 T>C), RS1000956948 (16:4754946 T>C), RS1000962264 (16:4763564 G>A,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

3 associations (top):

Study	Trait	p-value
GCST003542_157	Night sleep phenotypes	1.000000e-06
GCST007448_10	Normal facial asymmetry (angle of surface orientation score)	2.000000e-09
GCST011369_34	Iron status biomarkers (ferritin levels)	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009751	facial asymmetry measurement
EFO:0004459	ferritin measurement

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
Valproic Acid	affects cotreatment, decreases expression	3
Tobacco Smoke Pollution	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Selenium	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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