ZNF3

Summary

ZNF3 (zinc finger protein 3, HGNC:13089) is a protein-coding gene on chromosome 7q22.1, encoding Zinc finger protein 3 (P17036). Involved in cell differentiation and/or proliferation.

Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 7551 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multiple congenital anomalies/dysmorphic syndrome (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 102 total
• MANE Select transcript: NM_032924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13089
Approved symbol	ZNF3
Name	zinc finger protein 3
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	A8-51, KOX25, PP838, FLJ20216, HF.12, Zfp113
Ensembl gene	ENSG00000166526
Ensembl biotype	protein_coding
OMIM	194510
Entrez	7551

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 29 protein_coding, 5 retained_intron

ENST00000292393, ENST00000299667, ENST00000412947, ENST00000413658, ENST00000415068, ENST00000424697, ENST00000428683, ENST00000441298, ENST00000449785, ENST00000460331, ENST00000466121, ENST00000479192, ENST00000485892, ENST00000487620, ENST00000875768, ENST00000875769, ENST00000875770, ENST00000875771, ENST00000875772, ENST00000875773, ENST00000875774, ENST00000875775, ENST00000875776, ENST00000929076, ENST00000929077, ENST00000929078, ENST00000929079, ENST00000929080, ENST00000929081, ENST00000929082, ENST00000929083, ENST00000951836, ENST00000951837, ENST00000951838

RefSeq mRNA: 22 — MANE Select: NM_032924 NM_001278284, NM_001278287, NM_001278290, NM_001278291, NM_001278292, NM_001318135, NM_001318136, NM_001318137, NM_001362775, NM_001362776, NM_001362777, NM_001371210, NM_001371211, NM_001371212, NM_001371213, NM_001371214, NM_001371215, NM_001371216, NM_001371217, NM_001371218, NM_017715, NM_032924

CCDS: CCDS43618, CCDS43619, CCDS94152

Canonical transcript exons

ENST00000299667 — 6 exons

Exon	Start	End
ENSE00001103872	100079536	100079656
ENSE00001133692	100069973	100072212
ENSE00001181413	100081635	100081723
ENSE00001942113	100075135	100075261
ENSE00003570230	100077303	100077433
ENSE00003571595	100075542	100075630

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 92.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8937 / max 211.4608, expressed in 1786 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85136	14.6203	1780
85138	0.3856	139
85139	0.3230	121
85137	0.3053	132
85135	0.2594	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	92.05	gold quality
ganglionic eminence	UBERON:0004023	91.62	gold quality
secondary oocyte	CL:0000655	91.29	gold quality
cortical plate	UBERON:0005343	90.19	gold quality
sural nerve	UBERON:0015488	89.29	gold quality
embryo	UBERON:0000922	89.08	gold quality
ventricular zone	UBERON:0003053	89.03	gold quality
rectum	UBERON:0001052	88.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.38	gold quality
transverse colon	UBERON:0001157	87.64	gold quality
mucosa of transverse colon	UBERON:0004991	87.63	gold quality
left ovary	UBERON:0002119	87.59	gold quality
calcaneal tendon	UBERON:0003701	87.43	gold quality
small intestine	UBERON:0002108	87.41	gold quality
bronchial epithelial cell	CL:0002328	87.21	gold quality
right lobe of liver	UBERON:0001114	87.21	gold quality
body of uterus	UBERON:0009853	87.18	gold quality
right ovary	UBERON:0002118	87.15	gold quality
body of pancreas	UBERON:0001150	87.13	gold quality
apex of heart	UBERON:0002098	87.05	gold quality
left lobe of thyroid gland	UBERON:0001120	87.00	gold quality
left uterine tube	UBERON:0001303	86.99	gold quality
islet of Langerhans	UBERON:0000006	86.86	gold quality
colonic epithelium	UBERON:0000397	86.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.81	gold quality
metanephros cortex	UBERON:0010533	86.77	gold quality
right lobe of thyroid gland	UBERON:0001119	86.69	gold quality
endocervix	UBERON:0000458	86.63	gold quality
nipple	UBERON:0002030	86.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	69.92
E-ANND-3	yes	5.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting ZNF3, 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-4283	100.00	66.42	2097
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-544B	99.18	67.41	1632

Literature-anchored findings (GeneRIF, showing 2)

• ZNF3 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• ZNF3 regulates proliferation, migration and invasion through MMP1 and TWIST in colorectal cancer. (PMID:36789689)

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 3 — P17036 (reviewed: P17036)

Alternative names: Zinc finger protein HF.12, Zinc finger protein HZF3.1, Zinc finger protein KOX25

All UniProt accessions (6): C9J5S8, C9JE35, C9JK31, P17036, F8WA60, Q86U76

UniProt curated annotations — full annotation on UniProt →

Function. Involved in cell differentiation and/or proliferation.

Subcellular location. Nucleus.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P17036-1	1	yes
P17036-2	2

RefSeq proteins (22): NP_001265213, NP_001265216, NP_001265219, NP_001265220, NP_001265221, NP_001305064, NP_001305065, NP_001305066, NP_001349704, NP_001349705, NP_001349706, NP_001358139, NP_001358140, NP_001358141, NP_001358142, NP_001358143, NP_001358144, NP_001358145, NP_001358146, NP_001358147, NP_060185, NP_116313* (*=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 (23 total): zinc finger region 8, cross-link 6, sequence conflict 3, modified residue 2, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17036-F1	66.67	0.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 143, 419, 125, 151, 163, 173, 422, 431

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 124 (showing top): AFFAR_YY1_TARGETS_UP, TGCCTTA_MIR124A, TTTGCAC_MIR19A_MIR19B, CHEN_HOXA5_TARGETS_9HR_UP, CAGCTTT_MIR320, BOCHKIS_FOXA2_TARGETS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, CACTGCC_MIR34A_MIR34C_MIR449, CHENG_RESPONSE_TO_NICKEL_ACETATE, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, RAPA_EARLY_UP.V1_DN, E2F3_UP.V1_DN, SRC_UP.V1_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ARID5B_TARGET_GENES

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), leukocyte activation (GO:0045321), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), 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
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cellular developmental process	1
cell activation	1
immune system process	1
DNA-templated transcription	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
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

71 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
ZNF3	TRAF4	psi-mi:“MI:0915”(physical association)	0.720
TRAF4	ZNF3	psi-mi:“MI:0915”(physical association)	0.720
ZNF3	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
SSX2IP	ZNF3	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	ZNF3	psi-mi:“MI:0915”(physical association)	0.560
ZNF3	SSX2IP	psi-mi:“MI:0915”(physical association)	0.560
ZNF3	KRT27	psi-mi:“MI:0915”(physical association)	0.560
ZNF3	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
ZNF3	SF3B4	psi-mi:“MI:0915”(physical association)	0.560
ZNF3	MCC	psi-mi:“MI:0915”(physical association)	0.560
ZNF3	NDEL1	psi-mi:“MI:0915”(physical association)	0.560
ZNF3	LZTS1	psi-mi:“MI:0915”(physical association)	0.560
YJU2B	ZNF3	psi-mi:“MI:0915”(physical association)	0.560
ZNF3	ZNF3	psi-mi:“MI:0407”(direct interaction)	0.530
ZNF3	ZNF212	psi-mi:“MI:0407”(direct interaction)	0.530
ZNF212	ZNF3	psi-mi:“MI:0407”(direct interaction)	0.530
ZNF3	ACOT2	psi-mi:“MI:0915”(physical association)	0.400
ZNF3	ECE1	psi-mi:“MI:0915”(physical association)	0.370
Prkci	LLGL2	psi-mi:“MI:0914”(association)	0.350
Tsc1	PYGB	psi-mi:“MI:0914”(association)	0.350
Nfya	NFYB	psi-mi:“MI:0914”(association)	0.350
ZNF3	PTPRK	psi-mi:“MI:0914”(association)	0.350
CEP135	MCRIP1	psi-mi:“MI:0914”(association)	0.350
CEP135	WWP2	psi-mi:“MI:0914”(association)	0.350
ZNF3	POLR1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (58): TRAF4 (Two-hybrid), MTUS2 (Two-hybrid), SSX2IP (Two-hybrid), ZNF3 (Affinity Capture-MS), ZNF3 (Affinity Capture-MS), ZNF3 (Affinity Capture-MS), SHCBP1 (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), PTPRK (Affinity Capture-MS), ZNF3 (Two-hybrid), ZNF3 (Two-hybrid), ZNF3 (Two-hybrid), ZNF3 (Two-hybrid), ZNF3 (Two-hybrid), ZNF3 (Two-hybrid)

ESM2 similar proteins: A0A087WUV0, A0JNB1, A2VDP4, B2RUI1, P0CG31, P10072, P17025, P17036, P17097, P18733, P51814, Q08ER8, Q09FC8, Q0VGE8, Q14590, Q15937, Q16600, Q2M3X9, Q4V8A8, Q5CZA5, Q5R8G9, Q5RBX0, Q5VIY5, Q68DI1, Q6J6I6, Q6NX49, Q6P1L6, Q6PG37, Q6ZMS4, Q6ZMW2, Q80YP6, Q86UD4, Q86Y25, Q8IZ26, Q8N184, Q8NB42, Q8NEK5, Q8TAF7, Q8TF47, Q8WXB4

Diamond homologs: A1YEP8, A1YEQ3, A1YEV9, A1YEW3, A1YFC1, A1YFW2, A1YFW6, A1YG26, A1YG48, A1YG60, A1YGJ4, A1YGK6, A2T6E3, A2T6V8, A2T6W2, A2T712, A2T736, A2T7D2, A2T7D7, A2T7F2, A2T7F4, A2T7L7, A2T812, A6QNZ0, B2KFW1, O14709, O14771, O14978, O15535, O43309, O60304, O95125, P10073, P17022, P17028, P17029, P17036, P17040, P28698, P49910

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1142 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100072209:CGAT:C	acceptor_gain	1.0000
7:100072212:TC:T	acceptor_loss	1.0000
7:100072213:C:CC	acceptor_gain	1.0000
7:100072217:C:CT	acceptor_gain	1.0000
7:100075129:CCTTA:C	donor_loss	1.0000
7:100075130:CTTAC:C	donor_loss	1.0000
7:100075131:TTACC:T	donor_loss	1.0000
7:100075132:TA:T	donor_loss	1.0000
7:100075133:A:AC	donor_gain	1.0000
7:100075133:AC:A	donor_gain	1.0000
7:100075133:ACCCA:A	donor_loss	1.0000
7:100075134:C:CC	donor_gain	1.0000
7:100075134:CC:C	donor_gain	1.0000
7:100075150:T:A	donor_gain	1.0000
7:100075536:GCTCA:G	donor_loss	1.0000
7:100075537:CTCA:C	donor_loss	1.0000
7:100075538:TCA:T	donor_loss	1.0000
7:100075539:CA:C	donor_loss	1.0000
7:100075541:C:A	donor_loss	1.0000
7:100075627:AGAG:A	acceptor_gain	1.0000
7:100075628:GAG:G	acceptor_gain	1.0000
7:100075631:C:CC	acceptor_gain	1.0000
7:100072219:C:CT	acceptor_gain	0.9900
7:100072220:A:T	acceptor_gain	0.9900
7:100075134:CCCA:C	donor_gain	0.9900
7:100075167:A:AC	donor_gain	0.9900
7:100075273:CGTG:C	acceptor_gain	0.9900
7:100075540:A:AC	donor_gain	0.9900
7:100075541:C:CC	donor_gain	0.9900
7:100075626:AAGAG:A	acceptor_gain	0.9900

AlphaMissense

2975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100071773:G:C	F237L	0.998
7:100071773:G:T	F237L	0.998
7:100071775:A:G	F237L	0.998
7:100071437:G:C	F349L	0.997
7:100071437:G:T	F349L	0.997
7:100071439:A:G	F349L	0.997
7:100071756:A:G	L243P	0.997
7:100071269:G:C	F405L	0.996
7:100071269:G:T	F405L	0.996
7:100071271:A:G	F405L	0.996
7:100071521:G:C	F321L	0.996
7:100071521:G:T	F321L	0.996
7:100071523:A:G	F321L	0.996
7:100071605:G:C	F293L	0.996
7:100071605:G:T	F293L	0.996
7:100071607:A:G	F293L	0.996
7:100071689:G:C	F265L	0.996
7:100071689:G:T	F265L	0.996
7:100071691:A:G	F265L	0.996
7:100071746:A:C	H246Q	0.996
7:100071746:A:T	H246Q	0.996
7:100071353:A:C	F377L	0.995
7:100071353:A:T	F377L	0.995
7:100071355:A:G	F377L	0.995
7:100071744:T:G	Q247P	0.995
7:100071748:G:C	H246D	0.995
7:100071410:G:C	H358Q	0.994
7:100071410:G:T	H358Q	0.994
7:100071672:A:G	L271P	0.994
7:100071734:G:C	H250Q	0.994

dbSNP variants (sampled 300 via entrez): RS1000146276 (7:100075885 T>A,C), RS1000312949 (7:100076085 G>A), RS1000449680 (7:100081729 A>G), RS1000490278 (7:100070426 C>T), RS1000604846 (7:100082539 T>A), RS1000757180 (7:100082264 G>A,T), RS1000782847 (7:100066184 T>C), RS1000842564 (7:100070667 C>G,T), RS1000869215 (7:100076124 C>G), RS1001053132 (7:100070238 G>A), RS1001256106 (7:100077717 C>T), RS1001301328 (7:100063652 T>C), RS1001307075 (7:100077424 T>C), RS1001399229 (7:100070074 A>G), RS1001679192 (7:100069011 GGAGA>G,GGA,GGAGAGA)

Disease associations

OMIM: gene MIM:194510 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple congenital anomalies/dysmorphic syndrome	Limited	Autosomal recessive

Mondo (1): multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010002_259	Refractive error	3.000000e-16
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
enzacamene	increases expression, affects response to substance	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
nickel acetate	affects expression	1
abrine	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Dronabinol	decreases expression	1
Triiodothyronine	affects cotreatment, decreases expression	1
Valproic Acid	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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