ZNF568

Summary

ZNF568 (zinc finger protein 568, HGNC:25392) is a protein-coding gene on chromosome 19q13.12, encoding Zinc finger protein 568 (Q3ZCX4). Has transcriptional repression activity, partially through the recruitment of the corepressor TRIM28 but also has repression activity independently of this interaction.

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 embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 374900 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_198539

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25392
Approved symbol	ZNF568
Name	zinc finger protein 568
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	PISA, DKFZp686B0797
Ensembl gene	ENSG00000198453
Ensembl biotype	protein_coding
OMIM	617566
Entrez	374900

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000333987, ENST00000415168, ENST00000427117, ENST00000433993, ENST00000444991, ENST00000455427, ENST00000455817, ENST00000586353, ENST00000587130, ENST00000587857, ENST00000588596, ENST00000591887, ENST00000592567, ENST00000706166, ENST00000706167, ENST00000706168, ENST00000706169, ENST00000706170, ENST00000706171, ENST00000706172, ENST00000706173, ENST00000868355, ENST00000868356, ENST00000959600

RefSeq mRNA: 6 — MANE Select: NM_198539 NM_001204835, NM_001204836, NM_001204837, NM_001204838, NM_001204839, NM_198539

CCDS: CCDS42558, CCDS56092, CCDS56093, CCDS74351

Canonical transcript exons

ENST00000333987 — 7 exons

Exon	Start	End
ENSE00001478834	36917579	36917648
ENSE00002242066	36922586	36922846
ENSE00002500840	36937147	36937242
ENSE00002897798	36916332	36916591
ENSE00003466969	36936746	36936872
ENSE00003575827	36925200	36925258
ENSE00003994982	36949512	36952734

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 86.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8598 / max 114.8289, expressed in 1332 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175532	3.0587	1213
175535	0.7881	339
175533	0.5489	304
175536	0.4491	215
175537	0.0150	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	86.60	gold quality
ventricular zone	UBERON:0003053	85.43	gold quality
ganglionic eminence	UBERON:0004023	84.38	gold quality
cortical plate	UBERON:0005343	83.96	gold quality
endothelial cell	CL:0000115	83.35	gold quality
sural nerve	UBERON:0015488	81.47	gold quality
islet of Langerhans	UBERON:0000006	80.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.67	gold quality
stromal cell of endometrium	CL:0002255	79.51	gold quality
adrenal tissue	UBERON:0018303	78.34	gold quality
smooth muscle tissue	UBERON:0001135	78.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.05	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.82	gold quality
prefrontal cortex	UBERON:0000451	77.66	gold quality
tibial artery	UBERON:0007610	77.61	gold quality
popliteal artery	UBERON:0002250	77.59	gold quality
descending thoracic aorta	UBERON:0002345	77.22	gold quality
cerebellar cortex	UBERON:0002129	77.15	gold quality
hypothalamus	UBERON:0001898	77.09	gold quality
cerebellar hemisphere	UBERON:0002245	77.08	gold quality
aorta	UBERON:0000947	77.00	gold quality
spinal cord	UBERON:0002240	76.50	gold quality
thoracic aorta	UBERON:0001515	76.48	gold quality
ascending aorta	UBERON:0001496	76.43	gold quality
colonic epithelium	UBERON:0000397	76.35	gold quality
muscle of leg	UBERON:0001383	76.27	gold quality
cerebellum	UBERON:0002037	76.22	gold quality
corpus callosum	UBERON:0002336	76.10	gold quality
left ovary	UBERON:0002119	76.02	gold quality
anterior cingulate cortex	UBERON:0009835	75.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-11	no	136.23
E-ANND-3	no	5.01

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2568.1	ZNF568	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605368

miRNA regulators (miRDB)

91 targeting ZNF568, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385

Literature-anchored findings (GeneRIF, showing 2)

• M003-A06 is likely one of the genes contributing to the uniqueness of the human brain in comparison to other higher primates. (PMID:23071813)
• Influence of the interaction between p53 and ZNF568 on mitochondrial oxidative phosphorylation. (PMID:38944084)

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger protein 568 — Q3ZCX4 (reviewed: Q3ZCX4)

All UniProt accessions (16): A0A0C4DGP9, A0A1Y8EHF7, A0A994J5D8, A0A994J5R3, A0A994J5R8, A0A994J7L7, A0A994J7M0, A0A994J7Z8, C9JLX5, C9JXQ5, C9JZ58, C9K0F2, Q3ZCX4, K7EKY2, K7EL97, K7ELK8

UniProt curated annotations — full annotation on UniProt →

Function. Has transcriptional repression activity, partially through the recruitment of the corepressor TRIM28 but also has repression activity independently of this interaction. Essential during embryonic development, where it acts as a direct repressor of a placental-specific transcript of IGF2 in early development and regulates convergent extension movements required for axis elongation and tissue morphogenesis in all germ layers. Also important for normal morphogenesis of extraembryonic tissues including the yolk sac, extraembryonic mesoderm and placenta. May enhance proliferation or maintenance of neural stem cells.

Subunit / interactions. Interacts with TRIM28.

Subcellular location. Nucleus.

Polymorphism. Isoform 3 is highly polymorphic with three major alleles: H, C1 and C1. The H allele is found at higher frequencies in Japanese (0.71) and Taiwan Chinese (0.72) populations compared to European (0.45) and African (0.39) populations. The H allele may be associated with smaller head size in infants.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q3ZCX4-1	1	yes
Q3ZCX4-2	2
Q3ZCX4-3	3

RefSeq proteins (6): NP_001191764, NP_001191765, NP_001191766, NP_001191767, NP_001191768, NP_940941* (*=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 (36 total): zinc finger region 15, strand 6, turn 4, sequence conflict 3, splice variant 2, sequence variant 2, helix 2, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7W5Q	X-RAY DIFFRACTION	2.73
8J8N	ELECTRON MICROSCOPY	9.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3ZCX4-F1	73.94	0.21

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 93 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, WANG_LMO4_TARGETS_DN, GOBP_EMBRYO_DEVELOPMENT, GOBP_PLACENTA_DEVELOPMENT, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, BIDUS_METASTASIS_UP, GOBP_EMBRYONIC_ORGAN_DEVELOPMENT, GOBP_EMBRYONIC_PLACENTA_MORPHOGENESIS, STAT1_02, GOBP_EMBRYONIC_MORPHOGENESIS, YKACATTT_UNKNOWN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, STAT1_03

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), embryonic placenta morphogenesis (GO:0060669), regulation of DNA-templated transcription (GO:0006355), cellular developmental process (GO:0048869)

GO Molecular Function (8): transcription cis-regulatory region binding (GO:0000976), 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 transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

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	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
DNA-templated transcription	2
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
negative regulation of RNA biosynthetic process	1
embryonic placenta development	1
embryonic morphogenesis	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular process	1
developmental process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transition metal ion binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
nucleic acid binding	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF568	ANKRD13B	Q86YJ7	399
ZNF568	KRTAP19-7	Q3SYF9	398
ZNF568	KAT8	Q9H7Z6	386
ZNF568	OR6X1	Q8NH79	356
ZNF568	TRIM28	Q13263	353
ZNF568	OR13J1	Q8NGT2	327
ZNF568	DNAH17	Q9UFH2	326
ZNF568	OBSCN	Q5VST9	324
ZNF568	CNNM1	Q9NRU3	323
ZNF568	NDRG4	Q9ULP0	306
ZNF568	POM121L2	Q96KW2	301
ZNF568	OR4N2	Q8NGD1	297
ZNF568	PHETA1	Q8N4B1	296
ZNF568	DMRTA2	Q96SC8	292
ZNF568	TTK	P33981	291
ZNF568	NKAPL	Q5M9Q1	291

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
ZNF568	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): ZNF568 (Affinity Capture-RNA), ZNF568 (Positive Genetic), ZNF568 (Proximity Label-MS), ZNF568 (Proximity Label-MS), ZNF568 (Affinity Capture-RNA), ZNF568 (Affinity Capture-MS), ZNF568 (Affinity Capture-MS), ZNF568 (Affinity Capture-MS)

ESM2 similar proteins: A2VDQ7, A6NNF4, A8MQ14, A8MTY0, E9QAG8, O75290, O75373, P08043, P0CJ79, P10751, P17017, P17027, P17039, P35789, P51522, P51523, Q08AN1, Q14585, Q14587, Q3SYV7, Q3ZCX4, Q4R4C7, Q52M93, Q5MCW4, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6ECI4, Q6JLC9, Q6P3V2, Q6P5C7, Q6ZN57, Q86UE3, Q86XN6, Q86YE8, Q8C827, Q8IYB9, Q8N4W9, Q8N7M2

Diamond homologs: A0A1W2PQL4, A0JNB1, A0JPL0, A6NK53, A6QLU5, A6QPT6, A7MBI1, A8MT65, A8MUV8, A8MWA4, B2RXC5, B4DU55, B4DX44, E9PYI1, O14628, O75346, P0CH99, P0CI00, P17014, P17030, P17032, P17098, P51786, P85977, Q02386, Q06730, Q06732, Q0VAW7, Q12901, Q13360, Q14586, Q14588, Q14590, Q16587, Q2M3X9, Q2VY69, Q32M78, Q3ZCX4, Q49AA0, Q4R6J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1248 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36917578:GATCT:G	acceptor_gain	1.0000
19:36925259:G:GG	donor_gain	1.0000
19:36936743:CAG:C	acceptor_loss	1.0000
19:36936744:A:AC	acceptor_loss	1.0000
19:36936744:A:AG	acceptor_gain	1.0000
19:36936745:G:GG	acceptor_gain	1.0000
19:36936745:G:GT	acceptor_loss	1.0000
19:36936869:G:GG	donor_gain	1.0000
19:36936870:TGGGT:T	donor_loss	1.0000
19:36936871:GG:G	donor_gain	1.0000
19:36936872:GG:G	donor_gain	1.0000
19:36936873:G:GG	donor_gain	1.0000
19:36936873:GTAA:G	donor_loss	1.0000
19:36936874:T:A	donor_loss	1.0000
19:36937215:G:GT	donor_gain	1.0000
19:36938953:T:TA	acceptor_gain	1.0000
19:36917572:GTTTC:G	acceptor_loss	0.9900
19:36917573:TTTCA:T	acceptor_loss	0.9900
19:36917574:TTCA:T	acceptor_loss	0.9900
19:36917575:TCAG:T	acceptor_loss	0.9900
19:36917576:CAG:C	acceptor_loss	0.9900
19:36917577:A:AG	acceptor_gain	0.9900
19:36917577:AGAT:A	acceptor_loss	0.9900
19:36917578:G:GA	acceptor_gain	0.9900
19:36917578:GAT:G	acceptor_gain	0.9900
19:36917645:ATAGG:A	donor_loss	0.9900
19:36917648:GGT:G	donor_loss	0.9900
19:36917649:GTGA:G	donor_loss	0.9900
19:36917650:TG:T	donor_loss	0.9900
19:36917651:GAGTA:G	donor_loss	0.9900

AlphaMissense

4339 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:36950516:T:C	F455L	0.999
19:36950518:C:A	F455L	0.999
19:36950518:C:G	F455L	0.999
19:36950684:T:C	F511L	0.999
19:36950686:T:A	F511L	0.999
19:36950686:T:G	F511L	0.999
19:36950768:T:C	F539L	0.999
19:36950770:C:A	F539L	0.999
19:36950770:C:G	F539L	0.999
19:36950348:T:C	F399L	0.998
19:36950350:C:A	F399L	0.998
19:36950350:C:G	F399L	0.998
19:36950432:T:C	F427L	0.998
19:36950434:C:A	F427L	0.998
19:36950434:C:G	F427L	0.998
19:36950600:T:C	F483L	0.998
19:36950602:T:A	F483L	0.998
19:36950602:T:G	F483L	0.998
19:36950619:T:C	L489P	0.998
19:36950703:T:C	L517P	0.998
19:36950852:T:C	F567L	0.998
19:36950854:C:A	F567L	0.998
19:36950854:C:G	F567L	0.998
19:36950096:T:C	F315L	0.997
19:36950098:C:A	F315L	0.997
19:36950098:C:G	F315L	0.997
19:36950535:T:C	L461P	0.997
19:36950625:G:C	R491P	0.997
19:36950627:C:G	H492D	0.997
19:36950631:A:C	Q493P	0.997

dbSNP variants (sampled 300 via entrez): RS1000004322 (19:36959801 G>A,T), RS1000020396 (19:36968635 C>T), RS1000056648 (19:36960314 C>T), RS1000148084 (19:36959426 G>A,C), RS1000155235 (19:36961137 T>C), RS1000217091 (19:36951895 G>A,T), RS1000239526 (19:36981831 G>A), RS1000261706 (19:36978821 A>C,G), RS1000391817 (19:36973415 G>C), RS1000393774 (19:36988588 C>G), RS1000407768 (19:36923333 TCTC>T), RS1000418518 (19:36997052 A>G), RS1000481854 (19:36938496 A>G), RS1000550300 (19:36995443 G>A), RS1000576583 (19:36930121 A>T)

Disease associations

OMIM: gene MIM:617566 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST008521_13	Bitter beverage consumption	6.000000e-06
GCST011122_16	Walking pace	3.000000e-08
GCST90020024_565	A body shape index	1.000000e-10
GCST90020025_1644	Waist-to-hip ratio adjusted for BMI	4.000000e-09
GCST90020027_315	Waist-hip index	1.000000e-08
GCST90020029_48	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010089	bitter beverage consumption measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10405238	Toxicity	3	opioids	Nausea;Vomiting

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10405238	ZNF568	3	0.00	1	opioids

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
butyraldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
tebuconazole	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Cadmium	increases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1
Magnetite Nanoparticles	increases methylation	1

Clinical trials (associated diseases)

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