ZNF18

Summary

ZNF18 (zinc finger protein 18, HGNC:12969) is a protein-coding gene on chromosome 17p12, encoding Zinc finger protein 18 (P17022). 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 7566 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_001303281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12969
Approved symbol	ZNF18
Name	zinc finger protein 18
Location	17p12
Locus type	gene with protein product
Status	Approved
Aliases	ZKSCAN6, KOX11, HDSG1, Zfp535, ZNF535, ZSCAN38
Ensembl gene	ENSG00000154957
Ensembl biotype	protein_coding
OMIM	194524
Entrez	7566

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000322748, ENST00000454073, ENST00000577671, ENST00000580306, ENST00000580613, ENST00000580903, ENST00000582607

RefSeq mRNA: 3 — MANE Select: NM_001303281 NM_001303281, NM_001303282, NM_144680

CCDS: CCDS32568, CCDS76957

Canonical transcript exons

ENST00000580306 — 7 exons

Exon	Start	End
ENSE00001018582	11984113	11984197
ENSE00001018584	11990974	11991163
ENSE00001018586	11990462	11990550
ENSE00001121828	11983297	11983407
ENSE00001283554	11992443	11992911
ENSE00002233592	11997431	11997475
ENSE00003709061	11977439	11978744

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 88.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.0720 / max 54.2742, expressed in 1458 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164635	3.0720	1458

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.55	gold quality
blood	UBERON:0000178	84.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.78	gold quality
granulocyte	CL:0000094	82.46	gold quality
right lobe of liver	UBERON:0001114	81.30	gold quality
right testis	UBERON:0004534	81.17	gold quality
testis	UBERON:0000473	80.83	gold quality
left testis	UBERON:0004533	80.65	gold quality
apex of heart	UBERON:0002098	80.23	gold quality
calcaneal tendon	UBERON:0003701	79.93	gold quality
lower esophagus mucosa	UBERON:0035834	79.37	gold quality
bone marrow	UBERON:0002371	79.24	gold quality
spleen	UBERON:0002106	79.15	gold quality
colonic epithelium	UBERON:0000397	79.04	gold quality
cortical plate	UBERON:0005343	78.96	gold quality
gastrocnemius	UBERON:0001388	78.78	gold quality
mucosa of transverse colon	UBERON:0004991	78.61	gold quality
muscle of leg	UBERON:0001383	78.51	gold quality
skin of leg	UBERON:0001511	78.42	gold quality
lymph node	UBERON:0000029	78.21	gold quality
zone of skin	UBERON:0000014	78.16	gold quality
skeletal muscle tissue	UBERON:0001134	78.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.13	gold quality
leukocyte	CL:0000738	78.07	gold quality
muscle tissue	UBERON:0002385	77.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	77.92	gold quality
skin of abdomen	UBERON:0001416	77.80	gold quality
monocyte	CL:0000576	77.70	gold quality
tibial nerve	UBERON:0001323	77.67	gold quality
stromal cell of endometrium	CL:0002255	77.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.21

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2492.1	ZNF18	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605368

miRNA regulators (miRDB)

37 targeting ZNF18, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-198	98.70	67.32	920
HSA-MIR-496	98.66	69.80	931
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-1301-5P	98.09	66.62	495
HSA-MIR-6502-5P	98.09	66.73	495
HSA-MIR-6881-3P	98.04	68.24	1777

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	plagx	ENSDARG00000036855
danio_rerio	ovol1a	ENSDARG00000076472
danio_rerio	plagl2	ENSDARG00000076657
danio_rerio	ovol1b	ENSDARG00000078256
mus_musculus	Zkscan6	ENSMUSG00000018347
rattus_norvegicus	Zfp18	ENSRNOG00000003981
drosophila_melanogaster	hb	FBGN0001180
drosophila_melanogaster	CG12391	FBGN0033581
caenorhabditis_elegans		WBGENE00001824
caenorhabditis_elegans		WBGENE00003033
caenorhabditis_elegans		WBGENE00012385

Paralogs (29): ZNF446 (ENSG00000083838), REST (ENSG00000084093), ZNF174 (ENSG00000103343), OVOL3 (ENSG00000105261), PLAGL1 (ENSG00000118495), ZSCAN18 (ENSG00000121413), ZNF576 (ENSG00000124444), OVOL2 (ENSG00000125850), PLAGL2 (ENSG00000126003), ZSCAN5A (ENSG00000131848), ZSCAN29 (ENSG00000140265), ZSCAN32 (ENSG00000140987), ZSCAN1 (ENSG00000152467), ZKSCAN2 (ENSG00000155592), ZNF496 (ENSG00000162714), ZNF202 (ENSG00000166261), ZNF641 (ENSG00000167528), ZNF444 (ENSG00000167685), SCAND1 (ENSG00000171222), ZNF274 (ENSG00000171606), ZNF131 (ENSG00000172262), OVOL1 (ENSG00000172818), ZNF518A (ENSG00000177853), ZNF518B (ENSG00000178163), PLAG1 (ENSG00000181690), ZSCAN5B (ENSG00000197213), ZNF770 (ENSG00000198146), PEG3 (ENSG00000198300), ZSCAN5C (ENSG00000204532)

Protein

Protein identifiers

Zinc finger protein 18 — P17022 (reviewed: P17022)

Alternative names: Heart development-specific gene 1 protein, Zinc finger protein 535, Zinc finger protein KOX11, Zinc finger protein with KRAB and SCAN domains 6

All UniProt accessions (4): P17022, J3KSA1, J3KSC1, J3KTA0

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?
P17022-1	1	yes
P17022-2	2

RefSeq proteins (3): NP_001290210, NP_001290211, NP_653281 (=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

Pfam: PF00096, PF01352, PF02023

UniProt features (11 total): zinc finger region 5, domain 2, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17022-F1	55.29	0.05

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 63 (showing top): chr17p12, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_YELLOW_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, DACH1_TARGET_GENES, RBM34_TARGET_GENES, SFMBT1_TARGET_GENES, YBX1_TARGET_GENES, ZNF257_TARGET_GENES, MIR6881_3P, MIR6728_3P, MIR6802_3P

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

598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF18	UBE3B	Q7Z3V4	717
ZNF18	NCKAP5L	Q9HCH0	667
ZNF18	CDRT15	Q96T59	507
ZNF18	ZNF385B	Q569K4	491
ZNF18	OR8B4	Q96RC9	488
ZNF18	ZNF827	Q17R98	476
ZNF18	FBXO48	Q5FWF7	473
ZNF18	ZNF292	O60281	447
ZNF18	OR5AP2	Q8NGF4	447
ZNF18	TSHZ3	Q63HK5	437
ZNF18	BHLHA9	Q7RTU4	433
ZNF18	FOXD4L6	Q3SYB3	431
ZNF18	OR1L8	Q8NGR8	431
ZNF18	KRABD4	Q5JUW0	429
ZNF18	ZNF559	Q9BR84	417

IntAct

25 interactions, top by confidence:

A	B	Type	Score
CCNC	ZNF18	psi-mi:“MI:0915”(physical association)	0.670
ZNF18	CCNC	psi-mi:“MI:0915”(physical association)	0.670
TTC32	ZNF18	psi-mi:“MI:0915”(physical association)	0.560
ZNF18	TTC32	psi-mi:“MI:0915”(physical association)	0.560
ZNF18	ZNF446	psi-mi:“MI:0915”(physical association)	0.560
ZNF18	CPNE7	psi-mi:“MI:0915”(physical association)	0.560
ZNF18	ZMYM6	psi-mi:“MI:0914”(association)	0.530
	ZNF18	psi-mi:“MI:0915”(physical association)	0.370
CCL1	ZNF18	psi-mi:“MI:0915”(physical association)	0.370
CCL27	ZNF18	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
ZNF446	SEC16A	psi-mi:“MI:0914”(association)	0.350
ZNF18	RSL1D1	psi-mi:“MI:0914”(association)	0.350
ZNF446	ZNF18	psi-mi:“MI:0915”(physical association)	0.000
CPNE7	ZNF18	psi-mi:“MI:0915”(physical association)	0.000
CLIC6	ZNF18	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): ZNF18 (Two-hybrid), TTC32 (Two-hybrid), CCNC (Two-hybrid), UHRF1 (Affinity Capture-MS), SCAND1 (Affinity Capture-MS), ZNF174 (Affinity Capture-MS), ZNF446 (Affinity Capture-MS), ZNF24 (Affinity Capture-MS), ZNF483 (Affinity Capture-MS), ZMYM6 (Affinity Capture-MS), ZNF18 (Affinity Capture-MS), ZNF18 (Two-hybrid), CPNE7 (Two-hybrid), ZNF18 (Affinity Capture-RNA), ZMYM6 (Affinity Capture-MS)

ESM2 similar proteins: A1YEQ3, A1YEV9, A1YFW6, A1YG26, A1YG48, A1YG60, A2T6W2, A2T712, A2T736, A2T7L7, A6QNZ0, O14978, O15535, O95125, P17022, P17029, P49910, P51815, P59923, Q07231, Q15776, Q16670, Q1LZ87, Q3MJ62, Q3URR7, Q4KLI1, Q4R8H9, Q53GI3, Q5R670, Q5R741, Q5RJ54, Q63HK3, Q642B9, Q6P9G9, Q810A1, Q86W11, Q8BGS3, Q8CF60, Q8NF99, Q92670

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1405 predictions. Top by Δscore:

Variant	Effect	Δscore
17:11984114:T:TA	donor_gain	1.0000
17:11990546:CAGGG:C	acceptor_gain	1.0000
17:11991159:CTGAT:C	acceptor_gain	1.0000
17:11992509:T:TA	donor_gain	1.0000
17:11992910:CA:C	acceptor_gain	1.0000
17:11992912:C:CC	acceptor_gain	1.0000
17:11997426:CTCA:C	donor_loss	1.0000
17:11997428:CACCT:C	donor_loss	1.0000
17:11997429:A:AT	donor_loss	1.0000
17:11997430:C:G	donor_loss	1.0000
17:11978742:CTC:C	acceptor_gain	0.9900
17:11978744:CCTA:C	acceptor_loss	0.9900
17:11978745:C:CC	acceptor_gain	0.9900
17:11978745:CTAAA:C	acceptor_loss	0.9900
17:11984111:ACCT:A	donor_gain	0.9900
17:11984112:CCTC:C	donor_gain	0.9900
17:11990548:GGG:G	acceptor_gain	0.9900
17:11990550:GCTGA:G	acceptor_loss	0.9900
17:11990551:C:CC	acceptor_gain	0.9900
17:11990551:C:CG	acceptor_loss	0.9900
17:11990556:G:GC	acceptor_gain	0.9900
17:11990968:CCTCA:C	donor_loss	0.9900
17:11990969:CTCAC:C	donor_loss	0.9900
17:11990970:TCAC:T	donor_loss	0.9900
17:11990971:CACCT:C	donor_loss	0.9900
17:11990972:A:T	donor_loss	0.9900
17:11990973:C:A	donor_loss	0.9900
17:11991160:TGAT:T	acceptor_gain	0.9900
17:11991164:C:CC	acceptor_gain	0.9900
17:11992435:CTGCT:C	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002671 (17:12021906 G>A), RS1000044359 (17:11982475 G>A), RS1000052167 (17:12012652 A>G), RS1000256578 (17:12015987 C>T), RS1000288586 (17:12003378 T>C), RS1000293951 (17:12004570 C>T), RS1000314715 (17:12015409 T>C), RS1000348739 (17:12010416 G>T), RS1000421583 (17:12009475 C>A), RS1000597097 (17:12005830 T>C), RS1000667113 (17:12004187 C>A,T), RS1000787057 (17:12008337 A>G), RS1000981315 (17:11994973 G>A), RS1001090258 (17:11980538 A>G), RS1001256399 (17:11986924 T>C)

Disease associations

OMIM: gene MIM:194524 | 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
GCST009391_477	Metabolite levels	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010389	phosphatidylcholine 40:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression, affects cotreatment	1
Vehicle Emissions	affects expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Hydralazine	decreases expression, affects cotreatment	1
Niclosamide	increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	affects expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HD14	HEK293 eGFP-ZNF18	Transformed cell line	Female

Clinical trials (associated diseases)

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