ZNF322

Summary

ZNF322 (zinc finger protein 322, HGNC:23640) is a protein-coding gene on chromosome 6p22.2, encoding Zinc finger protein 322 (Q6U7Q0). Transcriptional activator.

ZNF322A is a member of the zinc-finger transcription factor family and may regulate transcriptional activation in MAPK (see MAPK1; MIM 176948) signaling pathways (Li et al., 2004 [PubMed 15555580]).

Source: NCBI Gene 79692 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_024639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23640
Approved symbol	ZNF322
Name	zinc finger protein 322
Location	6p22.2
Locus type	gene with protein product
Status	Approved
Aliases	bA457M11.3, bA457M11.2
Ensembl gene	ENSG00000181315
Ensembl biotype	protein_coding
OMIM	610847
Entrez	79692

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000415922, ENST00000456172, ENST00000461899, ENST00000465674, ENST00000471278, ENST00000480036, ENST00000607204, ENST00000622479, ENST00000894553, ENST00000894554, ENST00000894555, ENST00000894556, ENST00000894557, ENST00000922291, ENST00000922292, ENST00000922293, ENST00000950870

RefSeq mRNA: 4 — MANE Select: NM_024639 NM_001242797, NM_001242798, NM_001242799, NM_024639

CCDS: CCDS4617

Canonical transcript exons

ENST00000415922 — 4 exons

Exon	Start	End
ENSE00001367092	26643659	26643728
ENSE00001370461	26658558	26658646
ENSE00001958376	26634383	26638728
ENSE00003843118	26659441	26659746

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 95.10.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3162 / max 22.1598, expressed in 906 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72350	1.3162	906

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	95.10	gold quality
calcaneal tendon	UBERON:0003701	91.55	gold quality
ganglionic eminence	UBERON:0004023	88.73	gold quality
corpus callosum	UBERON:0002336	88.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.64	gold quality
ventricular zone	UBERON:0003053	87.52	gold quality
quadriceps femoris	UBERON:0001377	87.17	gold quality
endometrium	UBERON:0001295	87.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.63	gold quality
islet of Langerhans	UBERON:0000006	86.38	gold quality
adrenal tissue	UBERON:0018303	86.02	gold quality
cortical plate	UBERON:0005343	85.78	gold quality
smooth muscle tissue	UBERON:0001135	83.35	gold quality
urinary bladder	UBERON:0001255	83.25	gold quality
rectum	UBERON:0001052	82.72	gold quality
ovary	UBERON:0000992	82.50	gold quality
endocervix	UBERON:0000458	82.45	gold quality
body of uterus	UBERON:0009853	82.29	gold quality
stromal cell of endometrium	CL:0002255	82.25	gold quality
descending thoracic aorta	UBERON:0002345	82.11	gold quality
gall bladder	UBERON:0002110	82.09	gold quality
tibial artery	UBERON:0007610	82.03	gold quality
popliteal artery	UBERON:0002250	82.02	gold quality
left ovary	UBERON:0002119	81.97	gold quality
right ovary	UBERON:0002118	81.87	gold quality
myometrium	UBERON:0001296	81.77	gold quality
colonic epithelium	UBERON:0000397	81.71	gold quality
spinal cord	UBERON:0002240	81.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.66	gold quality
fallopian tube	UBERON:0003889	81.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	323.03
E-ANND-3	no	3.21

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
NANOG	Activation
POU5F1	Activation

JASPAR motifs

Motif	Name	Family
MA2493.1	ZNF322	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

miRNA regulators (miRDB)

189 targeting ZNF322, 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-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 9)

• These results suggest that ZNF322 is a member of the zinc-finger transcription factor family and may act as a positive regulator in gene transcription mediated by the MAPK signaling pathways. (PMID:15555580)
• ZNF322A overexpression transcriptionally dysregulates genes involved in cell growth and motility therefore contributes to lung tumorigenesis and poor prognosis (PMID:26279304)
• Our results reveal a new mechanism of ZNF322A oncoprotein destruction regulated by the CK1delta/GSK3beta/FBXW7a axis. Deregulation of this signaling axis results in ZNF322A overexpression and promotes cancer progression (PMID:28581525)
• Silencing ZNF322 recapitulated the cellular and molecular effects seen upon miR-4317 overexpression. (PMID:28880489)
• The ZNF322A-centered transcriptome promotes lung tumorigenesis and ZNF322A acts as a transcription suppressor of c-Myc to maintain lung cancer stem cell-like properties by shifting metabolism towards oxidative phosphorylation. (PMID:30258097)
• results reveal a new mechanism of AKT signaling in promoting ZNF322A protein stability and transcriptional activity in lung cancer cell, xenograft, and clinical models (PMID:31399647)
• ZNF322A-mediated protein phosphorylation induces autophagosome formation through modulation of IRS1-AKT glucose uptake and HSP-elicited UPR in lung cancer. (PMID:32576196)
• Dysregulated Kras/YY1/ZNF322A/Shh transcriptional axis enhances neo-angiogenesis to promote lung cancer progression. (PMID:32929330)
• Downregulation of microRNA-326 enhances ZNF322A expression, transcriptional activity and tumorigenic effects in lung cancer. (PMID:37647209)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp322a	ENSMUSG00000046351
rattus_norvegicus	Zfp322a	ENSRNOG00000017318

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 322 — Q6U7Q0 (reviewed: Q6U7Q0)

Alternative names: Zinc finger protein 322A, Zinc finger protein 388, Zinc finger protein 489

All UniProt accessions (2): Q6U7Q0, C9JP13

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator. Important for maintenance of pluripotency in embryonic stem cells. Binds directly to the POU5F1 distal enhancer and the NANOG proximal promoter, and enhances expression of both genes. Can also bind to numerous other gene promoters and regulates expression of many other pluripotency factors, either directly or indirectly. Promotes inhibition of MAPK signaling during embryonic stem cell differentiation.

Subunit / interactions. Interacts with POU5F1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous. Highly expressed in heart and skeletal muscle.

Miscellaneous. Significantly enhances POU5F1/OCT4-SOX2-KLF4-MYC (OSKM) mediated reprogramming of mouse embryonic fibroblasts into induced pluripotent stem cells, and can also substitute for SOX2 in this process.

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

RefSeq proteins (4): NP_001229726, NP_001229727, NP_001229728, NP_078915* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050758	Znf_C2H2-type	Family

Pfam: PF00096

UniProt features (19 total): zinc finger region 11, sequence conflict 6, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6U7Q0-F1	76.31	0.33

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 (1): 391

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_REGULATION_OF_STEM_CELL_POPULATION_MAINTENANCE, GUO_HEX_TARGETS_UP, AACTTT_UNKNOWN, NRF2_01, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, WALLACE_PROSTATE_CANCER_RACE_DN, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, CETS1P54_01, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of stem cell population maintenance (GO:1902459), 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), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription cis-regulatory region binding	2
transcription by RNA polymerase II	1
stem cell population maintenance	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
DNA-templated transcription	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
nucleic acid binding	1
transcription regulator activity	1
cation binding	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF322	ADD1	P35611	478
ZNF322	JUN	P05412	472
ZNF322	TKTL1	P51854	469
ZNF322	SCAND1	P57086	464
ZNF322	POM121L2	Q96KW2	445
ZNF322	FOS	P01100	443
ZNF322	MAPK1	P28482	428
ZNF322	UTP3	Q9NQZ2	396
ZNF322	ABT1	Q9ULW3	379
ZNF322	COX19	Q49B96	361
ZNF322	TAF5L	O75529	328
ZNF322	REXO5	Q96IC2	325
ZNF322	ZNF280A	P59817	321
ZNF322	HMGN4	O00479	315
ZNF322	TLNRD1	Q9H1K6	309

IntAct

0 interactions, top by confidence:

BioGRID (4): ZNF322 (Affinity Capture-MS), ZNF322 (Affinity Capture-RNA), ZNF322 (Protein-peptide), APP (Reconstituted Complex)

ESM2 similar proteins: P16372, P16374, P17030, P18712, P18717, P18719, P18720, P18721, P18722, P18724, P18726, P18727, P18730, P18731, P18734, P18735, P18739, P18740, P18741, P18743, P18744, P18746, P18747, P51503, P51504, P51505, P51506, P51507, P52741, P52743, Q147U1, Q15973, Q28151, Q3KP31, Q494X3, Q5RAM9, Q5REI6, Q5RF70, Q62513, Q62981

Diamond homologs: P17026, Q1LZC0, Q4R7X8, Q5R4X5, Q6U7Q0, Q8BZ89, Q8TBZ5, Q63HK3, Q8NF99, Q9Z1D9

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
GSK3B	“down-regulates quantity by destabilization”	ZNF322	phosphorylation
CSNK1D	“down-regulates quantity by destabilization”	ZNF322	phosphorylation
FBXW7	“down-regulates quantity by destabilization”	ZNF322	ubiquitination
AKT	“up-regulates activity”	ZNF322	phosphorylation
ZNF322	“up-regulates quantity by expression”	NANOG	“transcriptional regulation”
ZNF322	“up-regulates quantity by expression”	POU5F1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000185747 (6:26646322 T>C), RS1000379769 (6:26638933 C>A,G), RS1000501612 (6:26660576 G>A), RS1000705620 (6:26654148 A>G), RS1000725726 (6:26646026 C>A,T), RS1000956519 (6:26660888 G>C), RS1001330833 (6:26647589 T>C), RS1001381081 (6:26640495 T>G), RS1001416965 (6:26640729 C>T), RS1001595747 (6:26647996 A>G), RS1001657902 (6:26647213 T>C,G), RS1001707126 (6:26655676 C>T), RS1001821856 (6:26655428 C>G), RS1002387149 (6:26642026 C>T), RS1002419845 (6:26642406 T>C)

Disease associations

OMIM: gene MIM:610847 | 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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
sodium arsenite	increases abundance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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