ZNF426

Summary

ZNF426 (zinc finger protein 426, HGNC:20725) is a protein-coding gene on chromosome 19p13.2, encoding Zinc finger protein 426 (Q9BUY5). May be involved in transcriptional regulation.

Kaposi’s sarcoma-associated herpesvirus (KSHV) can be reactivated from latency by the viral protein RTA. The protein encoded by this gene is a zinc finger transcriptional repressor that interacts with RTA to modulate RTA-mediated reactivation of KSHV. While the encoded protein can repress KSHV reactivation, RTA can induce degradation of this protein through the ubiquitin-proteasome pathway to overcome the repression. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79088 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_024106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20725
Approved symbol	ZNF426
Name	zinc finger protein 426
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC2663
Ensembl gene	ENSG00000130818
Ensembl biotype	protein_coding
Entrez	79088

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 16 protein_coding, 1 nonsense_mediated_decay

ENST00000253115, ENST00000535489, ENST00000589289, ENST00000593003, ENST00000635810, ENST00000886875, ENST00000886876, ENST00000886877, ENST00000886878, ENST00000931988, ENST00000931989, ENST00000931990, ENST00000971895, ENST00000971896, ENST00000971897, ENST00000971898, ENST00000971899

RefSeq mRNA: 4 — MANE Select: NM_024106 NM_001300883, NM_001318055, NM_001318056, NM_024106

CCDS: CCDS12215, CCDS74279, CCDS82285

Canonical transcript exons

ENST00000253115 — 8 exons

Exon	Start	End
ENSE00000896843	9530985	9531067
ENSE00001288619	9538259	9538345
ENSE00001600349	9532845	9532925
ENSE00001624451	9533840	9533966
ENSE00001730250	9535188	9535279
ENSE00002867327	9523223	9529636
ENSE00003569290	9536208	9536356
ENSE00003798924	9538575	9538645

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 92.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7318 / max 91.0908, expressed in 1653 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179008	5.5135	1597
179009	2.8221	1370
179007	0.3962	191

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	92.16	gold quality
secondary oocyte	CL:0000655	90.46	gold quality
oral cavity	UBERON:0000167	89.71	gold quality
amniotic fluid	UBERON:0000173	89.67	gold quality
lower esophagus mucosa	UBERON:0035834	87.30	gold quality
parotid gland	UBERON:0001831	86.95	silver quality
epithelium of esophagus	UBERON:0001976	86.18	gold quality
esophagus squamous epithelium	UBERON:0006920	85.72	gold quality
pigmented layer of retina	UBERON:0001782	84.29	gold quality
retina	UBERON:0000966	84.27	gold quality
vena cava	UBERON:0004087	83.79	silver quality
calcaneal tendon	UBERON:0003701	83.78	gold quality
sperm	CL:0000019	83.48	gold quality
adrenal tissue	UBERON:0018303	83.19	gold quality
superficial temporal artery	UBERON:0001614	83.09	gold quality
lateral nuclear group of thalamus	UBERON:0002736	83.05	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.52	gold quality
lateral globus pallidus	UBERON:0002476	82.42	gold quality
corpus epididymis	UBERON:0004359	82.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.09	silver quality
heart right ventricle	UBERON:0002080	82.07	gold quality
pharyngeal mucosa	UBERON:0000355	81.89	gold quality
cauda epididymis	UBERON:0004360	81.87	gold quality
biceps brachii	UBERON:0001507	81.66	silver quality
germinal epithelium of ovary	UBERON:0001304	81.47	gold quality
cerebellar vermis	UBERON:0004720	81.43	gold quality
subthalamic nucleus	UBERON:0001906	81.26	gold quality
corpus callosum	UBERON:0002336	81.24	gold quality
mammalian vulva	UBERON:0000997	81.07	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.22
E-CURD-112	yes	3.47
E-MTAB-6386	no	199.06
E-CURD-46	no	32.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting ZNF426, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
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-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-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693

Literature-anchored findings (GeneRIF, showing 2)

• It was found that herpesvirus 8 RTA can induce K-RBP degradation through the ubiquitin-proteasome pathway and that two regions in RTA are responsible. (PMID:18216089)
• These findings suggest that the DNA-binding activity of K-RBP plays an important role in repressing viral promoter activity. (PMID:19592062)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp426	ENSMUSG00000059475
rattus_norvegicus	Zfp426	ENSRNOG00000033624

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

Zinc finger protein 426 — Q9BUY5 (reviewed: Q9BUY5)

All UniProt accessions (4): Q9BUY5, A0A1B0GUG0, K7EME3, K7ER43

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

RefSeq proteins (4): NP_001287812, NP_001304984, NP_001304985, NP_077011* (*=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, PF13465

UniProt features (16 total): zinc finger region 12, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUY5-F1	66.20	0.12

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 127 (showing top): BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, PALOMERO_GSI_SENSITIVITY_DN, MARSON_BOUND_BY_FOXP3_STIMULATED, CHEN_HOXA5_TARGETS_9HR_UP, chr19p13, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MARTENS_TRETINOIN_RESPONSE_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CBX5_TARGET_GENES, CHAF1B_TARGET_GENES, DIDO1_TARGET_GENES, FEV_TARGET_GENES, HAND1_TARGET_GENES, NFE2L1_TARGET_GENES

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (7): 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), transcription cis-regulatory region binding (GO:0000976), 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
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transition metal ion binding	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF426	WFDC12	Q8WWY7	521
ZNF426	PNMA5	Q96PV4	518
ZNF426	SPMAP1	A8MV24	418
ZNF426	KCNC2	Q96PR1	388
ZNF426	PNMA3	Q9UL41	383
ZNF426	RBPJ	Q06330	381
ZNF426	SAYSD1	Q9NPB0	375
ZNF426	LYSMD1	Q96S90	370
ZNF426	HEY1	Q9Y5J3	350
ZNF426	KRT1	P04264	320
ZNF426	KBTBD8	Q8NFY9	315
ZNF426	DCAF10	Q5QP82	313
ZNF426	FAM168B	A1KXE4	298
ZNF426	FBXL12	Q9NXK8	289
ZNF426	TLE2	Q04725	286

IntAct

131 interactions, top by confidence:

A	B	Type	Score
OPTN	ZNF426	psi-mi:“MI:0915”(physical association)	0.670
MAGOHB	ZNF426	psi-mi:“MI:0915”(physical association)	0.600
ZNF426	MAGOHB	psi-mi:“MI:0915”(physical association)	0.600
ZNF426	GLRX3	psi-mi:“MI:0915”(physical association)	0.560
MPPE1	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
ZNF426	CIB3	psi-mi:“MI:0915”(physical association)	0.560
ZNF426	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
TSGA10	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
USP25	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
CIB3	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
ZNF426	TSGA10	psi-mi:“MI:0915”(physical association)	0.560
ZNF426	USP25	psi-mi:“MI:0915”(physical association)	0.560
MTQ2	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
ZNF426	MTQ2	psi-mi:“MI:0915”(physical association)	0.560
DUSP4	ZNF426	psi-mi:“MI:0915”(physical association)	0.560
ZNF426	ARMC7	psi-mi:“MI:0915”(physical association)	0.560
ZNF426	CTNNA3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (56): ZNF426 (Two-hybrid), ZNF426 (Two-hybrid), ZNF426 (Two-hybrid), ZNF426 (Two-hybrid), TSGA10 (Two-hybrid), LZTS2 (Two-hybrid), CIB3 (Two-hybrid), ZNF426 (Two-hybrid), ZNF426 (Two-hybrid), ZNF426 (Two-hybrid), KRTAP4-12 (Two-hybrid), ZNF426 (Two-hybrid), CEP70 (Two-hybrid), ZNF426 (Two-hybrid), ZNF426 (Two-hybrid)

ESM2 similar proteins: A1L1L7, A3KN36, D3ZVT0, O43296, P08042, P13682, P16373, P17023, P17097, P52738, P85977, Q02975, Q12901, Q14590, Q14592, Q2M3W8, Q2VY69, Q4V8A8, Q571J5, Q5CZA5, Q5R7I8, Q5RB33, Q5RBX0, Q61751, Q61967, Q6GQR8, Q6PF04, Q6ZNG0, Q6ZS27, Q86Y25, Q8BFS8, Q8BQC8, Q8IZ26, Q8N782, Q8N9Z0, Q8R1D1, Q8TF47, Q8WTR7, Q96LW1, Q9BS31

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1136 predictions. Top by Δscore:

Variant	Effect	Δscore
19:9530978:ATCTT:A	donor_loss	1.0000
19:9530979:TCTTA:T	donor_loss	1.0000
19:9530980:CTTAC:C	donor_loss	1.0000
19:9530981:TTA:T	donor_loss	1.0000
19:9530982:TACCA:T	donor_loss	1.0000
19:9530984:C:A	donor_loss	1.0000
19:9531066:TC:T	acceptor_gain	1.0000
19:9531066:TCC:T	acceptor_loss	1.0000
19:9531067:CC:C	acceptor_gain	1.0000
19:9531067:CCTGA:C	acceptor_loss	1.0000
19:9531068:CT:C	acceptor_loss	1.0000
19:9531069:T:A	acceptor_loss	1.0000
19:9532923:CTC:C	acceptor_gain	1.0000
19:9532926:C:CC	acceptor_gain	1.0000
19:9532927:T:A	acceptor_loss	1.0000
19:9533834:TCTTA:T	donor_loss	1.0000
19:9533835:CTTAC:C	donor_loss	1.0000
19:9533836:TTACC:T	donor_loss	1.0000
19:9533837:TA:T	donor_loss	1.0000
19:9533838:A:AC	donor_gain	1.0000
19:9533839:C:CC	donor_gain	1.0000
19:9533839:C:CT	donor_loss	1.0000
19:9533839:CCTA:C	donor_gain	1.0000
19:9533842:A:AC	donor_gain	1.0000
19:9533843:C:CC	donor_gain	1.0000
19:9535183:TTTA:T	donor_loss	1.0000
19:9535184:TTA:T	donor_loss	1.0000
19:9535185:TACC:T	donor_loss	1.0000
19:9535186:A:T	donor_loss	1.0000
19:9535187:CCTG:C	donor_loss	1.0000

AlphaMissense

3675 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:9528590:G:C	F485L	0.998
19:9528590:G:T	F485L	0.998
19:9528592:A:G	F485L	0.998
19:9528842:A:C	F401L	0.998
19:9528842:A:T	F401L	0.998
19:9528844:A:G	F401L	0.998
19:9529010:G:C	F345L	0.998
19:9529010:G:T	F345L	0.998
19:9529012:A:G	F345L	0.998
19:9528642:C:G	R468P	0.997
19:9528674:A:C	F457L	0.997
19:9528674:A:T	F457L	0.997
19:9528676:A:G	F457L	0.997
19:9528899:A:C	H382Q	0.997
19:9528899:A:T	H382Q	0.997
19:9529094:G:C	F317L	0.997
19:9529094:G:T	F317L	0.997
19:9529096:A:G	F317L	0.997
19:9528506:G:C	F513L	0.996
19:9528506:G:T	F513L	0.996
19:9528508:A:G	F513L	0.996
19:9528909:A:G	L379P	0.996
19:9528926:G:C	F373L	0.996
19:9528926:G:T	F373L	0.996
19:9528928:A:G	F373L	0.996
19:9528647:G:C	H466Q	0.995
19:9528647:G:T	H466Q	0.995
19:9528649:G:C	H466D	0.995
19:9528657:A:G	L463P	0.995
19:9528635:G:C	H470Q	0.994

dbSNP variants (sampled 300 via entrez): RS1000167497 (19:9539552 G>A), RS1000182378 (19:9526483 G>T), RS1000269603 (19:9537837 A>G,T), RS1000509459 (19:9540607 C>T), RS1000558242 (19:9540315 T>A), RS1000592460 (19:9527437 C>A,T), RS1000621858 (19:9535165 A>C,G), RS1000922882 (19:9527640 A>G), RS1001039590 (19:9530305 A>C), RS1001093349 (19:9530079 C>G,T), RS1001316423 (19:9525690 T>C), RS1001372596 (19:9531568 G>C), RS1001379526 (19:9524875 A>G), RS1001416108 (19:9536597 T>G), RS1001425177 (19:9531373 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

1 associations (top):

Study	Trait	p-value
GCST010396_123	Gut microbiota (bacterial taxa, hurdle binary method)	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Air Pollutants	increases abundance, affects expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8H4	SEES3-1V human ZNF426, clone1	Embryonic stem cell	Male
CVCL_A8H5	SEES3-1V human ZNF426, clone2	Embryonic stem cell	Male
CVCL_A8H6	SEES3-1V human ZNF426, clone3	Embryonic stem cell	Male
CVCL_XW45	HEK293 eGFP-ZNF426	Transformed cell line	Female

Clinical trials (associated diseases)

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