ZNF425

Summary

ZNF425 (zinc finger protein 425, HGNC:20690) is a protein-coding gene on chromosome 7q36.1, encoding Zinc finger protein 425 (Q6IV72). Acts as a transcriptional repressor.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of DNA-templated transcription. Located in cytoplasm and nucleoplasm.

Source: NCBI Gene 155054 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_001001661

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20690
Approved symbol	ZNF425
Name	zinc finger protein 425
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204947
Ensembl biotype	protein_coding
OMIM	619507
Entrez	155054

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000378061, ENST00000483014, ENST00000484196, ENST00000495685, ENST00000926832, ENST00000951283

RefSeq mRNA: 1 — MANE Select: NM_001001661 NM_001001661

CCDS: CCDS34773

Canonical transcript exons

ENST00000378061 — 4 exons

Exon	Start	End
ENSE00001476104	149112137	149112295
ENSE00001476105	149118222	149118348
ENSE00001476106	149126196	149126324
ENSE00001944997	149102784	149105566

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 77.81.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0429 / max 15.1707, expressed in 638 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86728	1.0429	638

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.81	gold quality
secondary oocyte	CL:0000655	73.66	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.42	gold quality
ventricular zone	UBERON:0003053	73.14	gold quality
ganglionic eminence	UBERON:0004023	73.14	gold quality
stromal cell of endometrium	CL:0002255	73.04	gold quality
cortical plate	UBERON:0005343	72.96	gold quality
prefrontal cortex	UBERON:0000451	72.41	gold quality
lower esophagus mucosa	UBERON:0035834	70.77	gold quality
gastrocnemius	UBERON:0001388	70.66	gold quality
muscle of leg	UBERON:0001383	70.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.00	gold quality
right frontal lobe	UBERON:0002810	69.75	gold quality
cerebellar hemisphere	UBERON:0002245	69.08	gold quality
cerebellar cortex	UBERON:0002129	69.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	68.59	gold quality
anterior cingulate cortex	UBERON:0009835	68.59	gold quality
smooth muscle tissue	UBERON:0001135	68.00	gold quality
muscle tissue	UBERON:0002385	67.83	gold quality
cerebellum	UBERON:0002037	67.79	gold quality
lower esophagus	UBERON:0013473	67.71	gold quality
skeletal muscle tissue	UBERON:0001134	67.68	gold quality
frontal cortex	UBERON:0001870	67.68	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.67	gold quality
body of uterus	UBERON:0009853	67.59	gold quality
islet of Langerhans	UBERON:0000006	67.58	gold quality
neocortex	UBERON:0001950	67.51	gold quality
popliteal artery	UBERON:0002250	67.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

52 targeting ZNF425, 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-3688-3P	99.97	72.02	2834
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-504-3P	99.30	67.18	1745

Literature-anchored findings (GeneRIF, showing 1)

• Over-expression of ZNF425 inhibits the transcriptional activities of SRE, AP-1, and SRF. Deletion analysis indicates that the C2H2 domain is the main region responsible for the repression. (PMID:21266108)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF582 (ENSG00000018869), 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)

Protein

Protein identifiers

Zinc finger protein 425 — Q6IV72 (reviewed: Q6IV72)

All UniProt accessions (3): A0A090N7U3, Q6IV72, C9JNW7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional repressor.

Subcellular location. Nucleus. Cytoplasm.

Domain organisation. The C2H2 domain is necessary for the transcriptional repression.

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

RefSeq proteins (1): NP_001001661* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR003655	aKRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050589	Ikaros_C2H2-ZF	Family

Pfam: PF00096, PF01352

UniProt features (25 total): zinc finger region 19, sequence conflict 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IV72-F1	72.51	0.03

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins

MSigDB gene sets: 50 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CREB3L4_TARGET_GENES, DLX4_TARGET_GENES, ID1_TARGET_GENES, ID2_TARGET_GENES, NAB2_TARGET_GENES, RBM34_TARGET_GENES, SNIP1_TARGET_GENES, TOP2B_TARGET_GENES, ZNF30_TARGET_GENES, ZNF610_TARGET_GENES

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), 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 (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
DNA-templated transcription	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
negative regulation of RNA biosynthetic process	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
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF425	C7orf33	Q8WU49	507
ZNF425	DRC11L	A6NCM1	481
ZNF425	ZNF280B	Q86YH2	474
ZNF425	ANTXR1	Q9H6X2	452
ZNF425	A0A087WTJ2	A0A087WTJ2	448
ZNF425	OR8B8	Q15620	448
ZNF425	TMBIM6	P55061	447
ZNF425	ZBED10P	Q96FA7	446
ZNF425	WDR86	Q86TI4	420
ZNF425	LRRC61	Q9BV99	419
ZNF425	YPEL3	P61236	406
ZNF425	ACOT13	Q9NPJ3	398
ZNF425	PCMT1	P22061	397
ZNF425	UGGT2	Q9NYU1	395
ZNF425	CEP170	Q5SW79	387

IntAct

4 interactions, top by confidence:

A	B	Type	Score
KRTAP10-7	ZNF425	psi-mi:“MI:0915”(physical association)	0.560
ZNF425	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1): KRTAP10-7 (Two-hybrid)

ESM2 similar proteins: A3KN32, A3KN36, O14709, O43296, O75123, P15622, P16373, P17023, P17031, P17097, P52736, P85977, Q07230, Q12901, Q14929, Q29RZ4, Q4V8A8, Q571J5, Q5CZA5, Q5JNZ3, Q5R7I8, Q5RBX0, Q5RBY9, Q5RCD9, Q5RCX4, Q61751, Q61967, Q6GQR8, Q6IV72, Q6NX45, Q6PK81, Q6ZMS4, Q7TNU6, Q7TSH9, Q7Z398, Q7Z7L9, Q8BI99, Q8BIQ3, Q8BLB0, Q8IZ26

Diamond homologs: A2A761, A6NFI3, A6NK75, A6NM28, A6NP11, A6QPT6, A8MQ14, A8MTY0, A8MUV8, B4DU55, B4DX44, B4DXR9, O60290, O75373, O75437, O95780, P0DPD5, P17014, P17032, P35789, P51523, P52736, P52738, Q02525, Q03923, Q03936, Q05481, Q06730, Q06732, Q14587, Q14593, Q14929, Q15928, Q16587, Q2KI58, Q3B7M4, Q3SXZ3, Q3U133, Q49AA0, Q4R6C2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

520 predictions. Top by Δscore:

Variant	Effect	Δscore
7:149112294:CC:C	acceptor_gain	1.0000
7:149112295:CC:C	acceptor_gain	1.0000
7:149118216:TCTTA:T	donor_loss	1.0000
7:149118217:CTTA:C	donor_loss	1.0000
7:149118218:TTACC:T	donor_loss	1.0000
7:149118219:TAC:T	donor_loss	1.0000
7:149118220:A:AC	donor_gain	1.0000
7:149118220:AC:A	donor_gain	1.0000
7:149118221:C:CC	donor_gain	1.0000
7:149118221:C:G	donor_loss	1.0000
7:149118221:CC:C	donor_gain	1.0000
7:149118310:C:CT	acceptor_gain	1.0000
7:149118310:C:T	acceptor_gain	1.0000
7:149118348:CCTG:C	acceptor_loss	1.0000
7:149118349:CTG:C	acceptor_loss	1.0000
7:149112130:TAC:T	donor_loss	0.9900
7:149112131:A:AC	donor_gain	0.9900
7:149112131:AC:A	donor_loss	0.9900
7:149112132:C:CC	donor_gain	0.9900
7:149112133:TCACC:T	donor_loss	0.9900
7:149112134:CA:C	donor_loss	0.9900
7:149112135:A:AC	donor_gain	0.9900
7:149112135:A:T	donor_loss	0.9900
7:149112136:C:CC	donor_gain	0.9900
7:149112136:C:CT	donor_loss	0.9900
7:149112153:T:A	donor_gain	0.9900
7:149112292:TACC:T	acceptor_gain	0.9900
7:149118215:ATCTT:A	donor_loss	0.9900
7:149118216:T:C	donor_gain	0.9900
7:149118220:ACC:A	donor_gain	0.9900

AlphaMissense

5025 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:149103913:A:G	L653P	0.997
7:149103930:G:C	F647L	0.997
7:149103930:G:T	F647L	0.997
7:149103932:A:G	F647L	0.997
7:149104602:G:C	F423L	0.997
7:149104602:G:T	F423L	0.997
7:149104604:A:G	F423L	0.997
7:149104686:G:C	F395L	0.997
7:149104686:G:T	F395L	0.997
7:149104688:A:G	F395L	0.997
7:149104770:G:C	F367L	0.997
7:149104770:G:T	F367L	0.997
7:149104772:A:G	F367L	0.997
7:149103678:G:C	F731L	0.996
7:149103678:G:T	F731L	0.996
7:149103680:A:G	F731L	0.996
7:149103903:G:C	H656Q	0.996
7:149103903:G:T	H656Q	0.996
7:149104014:G:C	F619L	0.996
7:149104014:G:T	F619L	0.996
7:149104016:A:G	F619L	0.996
7:149104266:G:C	F535L	0.996
7:149104266:G:T	F535L	0.996
7:149104268:A:G	F535L	0.996
7:149104323:G:C	H516Q	0.996
7:149104323:G:T	H516Q	0.996
7:149104350:A:C	F507L	0.996
7:149104350:A:T	F507L	0.996
7:149104352:A:G	F507L	0.996
7:149104182:G:C	F563L	0.995

dbSNP variants (sampled 300 via entrez): RS1000049038 (7:149125009 A>C), RS1000103298 (7:149122653 G>A), RS1000177579 (7:149109983 T>A,C), RS1000398837 (7:149125310 G>A), RS1001074488 (7:149106740 G>A), RS1001141235 (7:149112580 T>A), RS1001201127 (7:149104968 C>G,T), RS1001242820 (7:149108206 C>T), RS1001413335 (7:149102627 C>G,T), RS1001419438 (7:149110956 G>A), RS1001546049 (7:149117387 G>A), RS1001590807 (7:149108483 C>T), RS1001830286 (7:149123663 T>C), RS1001935328 (7:149116313 G>A), RS1002176463 (7:149123328 A>G,T)

Disease associations

OMIM: gene MIM:619507 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
sodium arsenite	increases expression	1
zinc chromate	increases abundance, increases expression	1
ferrous chloride	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
NSC668394	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Ethanol	increases expression	1
Benzo(a)pyrene	increases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Palmitic Acid	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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