ZNF12

Summary

ZNF12 (zinc finger protein 12, HGNC:12902) is a protein-coding gene on chromosome 7p22.1, encoding Zinc finger protein 12 (P17014). Transcriptional repressor which suppresses activation protein 1 (AP-1)- and serum response element (SRE)-mediated transcriptional activity.

This gene is a member of the krueppel C2H2-type zinc-finger protein family and encodes a protein with eight C2H2-type zinc fingers and a KRAB domain. This nuclear protein is involved in developmental control of gene expression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 7559 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_016265

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12902
Approved symbol	ZNF12
Name	zinc finger protein 12
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	KOX3, GIOT-3
Ensembl gene	ENSG00000164631
Ensembl biotype	protein_coding
OMIM	194536
Entrez	7559

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000342651, ENST00000394917, ENST00000404360, ENST00000405858, ENST00000491565

RefSeq mRNA: 2 — MANE Select: NM_016265 NM_006956, NM_016265

CCDS: CCDS47538, CCDS47539

Canonical transcript exons

ENST00000405858 — 5 exons

Exon	Start	End
ENSE00001391428	6697339	6697434
ENSE00001560010	6688433	6692703
ENSE00003604368	6697685	6697811
ENSE00003687188	6705159	6705223
ENSE00003848410	6706432	6706947

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 93.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1004 / max 137.5056, expressed in 1792 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82666	13.1004	1792

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	93.90	gold quality
caput epididymis	UBERON:0004358	93.89	gold quality
corpus epididymis	UBERON:0004359	93.40	gold quality
cardia of stomach	UBERON:0001162	93.22	gold quality
mammary duct	UBERON:0001765	93.02	gold quality
superficial temporal artery	UBERON:0001614	92.62	gold quality
pylorus	UBERON:0001166	92.40	gold quality
nipple	UBERON:0002030	91.89	gold quality
pericardium	UBERON:0002407	91.77	gold quality
lower lobe of lung	UBERON:0008949	91.56	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.51	gold quality
oral cavity	UBERON:0000167	91.36	gold quality
trabecular bone tissue	UBERON:0002483	91.26	gold quality
epithelium of mammary gland	UBERON:0003244	91.19	gold quality
seminal vesicle	UBERON:0000998	91.04	gold quality
urethra	UBERON:0000057	90.80	gold quality
jejunal mucosa	UBERON:0000399	90.69	gold quality
renal medulla	UBERON:0000362	90.37	gold quality
mammalian vulva	UBERON:0000997	90.28	gold quality
cartilage tissue	UBERON:0002418	89.84	gold quality
upper leg skin	UBERON:0004262	89.84	gold quality
bronchial epithelial cell	CL:0002328	89.78	gold quality
skin of hip	UBERON:0001554	89.71	gold quality
pigmented layer of retina	UBERON:0001782	89.39	gold quality
jejunum	UBERON:0002115	89.28	gold quality
parietal pleura	UBERON:0002400	89.24	gold quality
germinal epithelium of ovary	UBERON:0001304	89.22	gold quality
penis	UBERON:0000989	89.17	gold quality
visceral pleura	UBERON:0002401	89.01	gold quality
superior surface of tongue	UBERON:0007371	88.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

111 targeting ZNF12, 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-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514

Literature-anchored findings (GeneRIF, showing 2)

• A zinc finger protein with a RBaK-like RB-binding domain, inhibits AP-1- and SRE-mediated transcriptional activity (PMID:16806083)
• Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. (PMID:33402679)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp12	ENSMUSG00000029587
rattus_norvegicus	Zfp12	ENSRNOG00000006958

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), ZNF3 (ENSG00000166526)

Protein

Protein identifiers

Zinc finger protein 12 — P17014 (reviewed: P17014)

Alternative names: Gonadotropin-inducible ovary transcription repressor 3, Zinc finger protein 325, Zinc finger protein KOX3

All UniProt accessions (2): P17014, H9KV98

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor which suppresses activation protein 1 (AP-1)- and serum response element (SRE)-mediated transcriptional activity.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed in various adult tissues and embryonic developmental stages (isoform 3).

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

Isoforms (5)

UniProt ID	Names	Canonical?
P17014-1	1	yes
P17014-2	2
P17014-3	3
P17014-4	4
P17014-5	5

RefSeq proteins (2): NP_008887, NP_057349* (*=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
IPR050589	Ikaros_C2H2-ZF	Family

Pfam: PF00096, PF01352, PF13465

UniProt features (40 total): zinc finger region 15, cross-link 15, splice variant 4, sequence conflict 4, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17014-F1	70.36	0.13

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 (15): 3, 98, 179, 182, 209, 215, 224, 239, 267, 309, 323, 337, 365, 544, 547

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 101 (showing top): TGCGCANK_UNKNOWN, BILD_SRC_ONCOGENIC_SIGNATURE, chr7p22, BLALOCK_ALZHEIMERS_DISEASE_UP, RYTTCCTG_ETS2_B, GCM_NF2, DANG_BOUND_BY_MYC, BENPORATH_MYC_MAX_TARGETS, HAMAI_APOPTOSIS_VIA_TRAIL_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, DUTERTRE_ESTRADIOL_RESPONSE_24HR_DN, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ATF5_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 (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), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813)

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	2
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	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
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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

1018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF12	TADA3	O75528	525
ZNF12	BTBD9	Q96Q07	512
ZNF12	SLCO6A1	Q86UG4	474
ZNF12	ACYP1	P07311	436
ZNF12	TRIM39	Q9HCM9	431
ZNF12	ZBTB1	Q9Y2K1	423
ZNF12	DAGLB	Q8NCG7	376
ZNF12	INTS15	Q96N11	370
ZNF12	KDELR2	P33947	352
ZNF12	EEIG2	Q5T8I3	327
ZNF12	FAM220A	Q7Z4H9	316
ZNF12	DCLK3	Q9C098	315
ZNF12	MSANTD3	Q96H12	311
ZNF12	C11orf96	Q7Z7L8	306
ZNF12	RBM12B	Q8IXT5	288

IntAct

21 interactions, top by confidence:

A	B	Type	Score
ZNF12	MCC	psi-mi:“MI:0915”(physical association)	0.560
ZNF12	MDFI	psi-mi:“MI:0915”(physical association)	0.560
ZNF12	CARD10	psi-mi:“MI:0915”(physical association)	0.560
ZNF12	NDEL1	psi-mi:“MI:0915”(physical association)	0.560
ZNF12	STX1A	psi-mi:“MI:0915”(physical association)	0.560
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
YJU2B	RCCD1	psi-mi:“MI:0914”(association)	0.530
DCLK3	ZNF12	psi-mi:“MI:0915”(physical association)	0.370
ZNF12	DCD	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
ZNF12	STX1A	psi-mi:“MI:0915”(physical association)	0.000
ZNF12	MCC	psi-mi:“MI:0915”(physical association)	0.000
ZNF12	MDFI	psi-mi:“MI:0915”(physical association)	0.000
ZNF12	CARD10	psi-mi:“MI:0915”(physical association)	0.000
ZNF12	NDEL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): ZNF12 (Affinity Capture-MS), ZNF12 (Affinity Capture-MS), ZNF12 (Affinity Capture-MS), ZNF12 (Affinity Capture-MS), ZNF12 (Affinity Capture-RNA), ZNF12 (Affinity Capture-RNA), ZNF12 (Two-hybrid), ZNF12 (Two-hybrid), ZNF12 (Two-hybrid), NDEL1 (Two-hybrid), MCC (Two-hybrid), ZNF12 (Affinity Capture-MS), ZNF12 (Affinity Capture-MS), ZNF12 (Affinity Capture-MS), ZNF12 (Affinity Capture-MS)

ESM2 similar proteins: A2VDP4, A6NHJ4, O94892, P0CJ79, P17014, P17021, P17025, P17032, P17035, P18733, P51508, P51814, Q06730, Q06732, Q09FC8, Q0VGE8, Q14586, Q32M78, Q3MIS6, Q5JVG2, Q5R4K8, Q5R9S5, Q5RBQ3, Q5RCJ2, Q5RER9, Q5TYW1, Q5VIY5, Q6P560, Q6PDB4, Q6ZMW2, Q6ZN06, Q6ZNA1, Q76KX8, Q7L2R6, Q86Y25, Q8N184, Q8N823, Q8N883, Q8N8J6, Q8NEP9

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1016 predictions. Top by Δscore:

Variant	Effect	Δscore
7:6692704:C:CC	acceptor_gain	1.0000
7:6697684:CCCA:C	donor_gain	1.0000
7:6697724:C:A	donor_gain	1.0000
7:6706430:AC:A	donor_gain	1.0000
7:6706430:ACCCT:A	donor_gain	1.0000
7:6706431:CC:C	donor_gain	1.0000
7:6706431:CCCTC:C	donor_gain	1.0000
7:6692701:CAT:C	acceptor_gain	0.9900
7:6692703:TCTA:T	acceptor_loss	0.9900
7:6692704:C:T	acceptor_loss	0.9900
7:6692705:T:G	acceptor_loss	0.9900
7:6697433:CC:C	acceptor_gain	0.9900
7:6697434:CC:C	acceptor_gain	0.9900
7:6697723:T:TA	donor_gain	0.9900
7:6706425:GACTT:G	donor_loss	0.9900
7:6706426:ACTTA:A	donor_loss	0.9900
7:6706427:CTTAC:C	donor_loss	0.9900
7:6706428:TTACC:T	donor_loss	0.9900
7:6706430:A:AC	donor_gain	0.9900
7:6706430:A:C	donor_loss	0.9900
7:6706431:C:CC	donor_gain	0.9900
7:6706431:CCCT:C	donor_gain	0.9900
7:6692699:TTCAT:T	acceptor_gain	0.9800
7:6697431:TACC:T	acceptor_gain	0.9800
7:6697683:AC:A	donor_gain	0.9800
7:6697684:CC:C	donor_gain	0.9800
7:6697687:A:AC	donor_gain	0.9800
7:6697688:C:CC	donor_gain	0.9800
7:6697736:T:C	donor_gain	0.9800
7:6705151:ACACT:A	donor_loss	0.9800

AlphaMissense

4630 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:6691016:G:C	F642L	1.000
7:6691016:G:T	F642L	1.000
7:6691018:A:G	F642L	1.000
7:6691068:C:G	R625P	1.000
7:6691083:A:G	L620P	1.000
7:6691184:G:C	F586L	1.000
7:6691184:G:T	F586L	1.000
7:6691186:A:G	F586L	1.000
7:6690999:A:G	L648P	0.999
7:6691011:C:G	R644P	0.999
7:6691075:G:C	H623D	0.999
7:6691100:G:C	F614L	0.999
7:6691100:G:T	F614L	0.999
7:6691102:A:G	F614L	0.999
7:6691161:C:G	R594P	0.999
7:6691167:A:G	L592P	0.999
7:6691243:G:C	H567D	0.999
7:6691251:A:G	L564P	0.999
7:6691352:G:C	F530L	0.999
7:6691352:G:T	F530L	0.999
7:6691354:A:G	F530L	0.999
7:6691419:A:G	L508P	0.999
7:6691436:G:C	F502L	0.999
7:6691436:G:T	F502L	0.999
7:6691438:A:G	F502L	0.999
7:6691520:G:C	F474L	0.999
7:6691520:G:T	F474L	0.999
7:6691522:A:G	F474L	0.999
7:6691587:A:G	L452P	0.999
7:6691671:A:G	L424P	0.999

dbSNP variants (sampled 300 via entrez): RS1000281893 (7:6707172 C>A,G), RS1000583174 (7:6708610 G>A), RS1000612882 (7:6708369 A>C), RS1000664202 (7:6707794 A>G), RS1000701428 (7:6707318 A>C,G), RS1000928668 (7:6703356 A>G), RS1001070600 (7:6690198 G>A), RS1001125022 (7:6703673 G>A), RS1001136407 (7:6697267 C>G,T), RS1001306472 (7:6706621 T>G), RS1001509774 (7:6705855 T>G), RS1001597890 (7:6688090 T>C), RS1001706134 (7:6695055 C>T), RS1001738024 (7:6706404 G>A), RS1001753559 (7:6693780 T>A)

Disease associations

OMIM: gene MIM:194536 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002783_305	Body mass index	3.000000e-06
GCST002783_33	Body mass index	4.000000e-06
GCST002814_4	Alzheimer’s disease (APOE e4 interaction)	3.000000e-08
GCST004604_119	Hematocrit	1.000000e-10
GCST004615_45	Hemoglobin concentration	4.000000e-10
GCST010083_137	Hemoglobin levels	6.000000e-07
GCST90002384_72	Hemoglobin	4.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007659	APOE carrier status
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	4
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Coumestrol	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Selenium	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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