ZNF721

Summary

ZNF721 (zinc finger protein 721, HGNC:29425) is a protein-coding gene on chromosome 4p16.3, encoding Zinc finger protein 721 (Q8TF20). May be involved in transcriptional regulation.

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 170960 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 185 total
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_133474

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29425
Approved symbol	ZNF721
Name	zinc finger protein 721
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1982
Ensembl gene	ENSG00000182903
Ensembl biotype	protein_coding
Entrez	170960

Gene structure

Transcript identifiers

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

ENST00000338977, ENST00000505900, ENST00000506646, ENST00000507078, ENST00000511833, ENST00000515578

RefSeq mRNA: 1 — MANE Select: NM_133474 NM_133474

CCDS: CCDS46991

Canonical transcript exons

ENST00000511833 — 3 exons

Exon	Start	End
ENSE00002074759	499056	499156
ENSE00002324092	439988	444432
ENSE00003527083	472575	472701

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 95.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.6467 / max 58.5389, expressed in 1681 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50986	24.9100	1749
50987	4.6467	1681

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.84	gold quality
secondary oocyte	CL:0000655	94.90	gold quality
epithelial cell of pancreas	CL:0000083	94.61	gold quality
endothelial cell	CL:0000115	94.22	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.81	gold quality
germinal epithelium of ovary	UBERON:0001304	91.72	gold quality
epithelium of nasopharynx	UBERON:0001951	91.60	gold quality
cortical plate	UBERON:0005343	91.50	gold quality
calcaneal tendon	UBERON:0003701	90.91	gold quality
islet of Langerhans	UBERON:0000006	90.20	gold quality
ventricular zone	UBERON:0003053	90.16	gold quality
tonsil	UBERON:0002372	89.63	gold quality
primary visual cortex	UBERON:0002436	89.29	gold quality
palpebral conjunctiva	UBERON:0001812	89.00	gold quality
parietal pleura	UBERON:0002400	88.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.85	gold quality
middle temporal gyrus	UBERON:0002771	88.79	silver quality
amniotic fluid	UBERON:0000173	88.55	gold quality
visceral pleura	UBERON:0002401	88.43	gold quality
corpus callosum	UBERON:0002336	88.11	gold quality
ganglionic eminence	UBERON:0004023	87.95	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.70	gold quality
pancreas	UBERON:0001264	87.67	gold quality
pigmented layer of retina	UBERON:0001782	87.63	gold quality
lymph node	UBERON:0000029	87.62	gold quality
gingival epithelium	UBERON:0001949	87.59	gold quality
cerebellar hemisphere	UBERON:0002245	87.39	gold quality
granulocyte	CL:0000094	87.38	gold quality
cerebellar cortex	UBERON:0002129	87.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.37
E-MTAB-7303	no	95.90

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2526.1	ZNF721	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

98 targeting ZNF721, 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-3064-3P	100.00	70.09	1254
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp974	ENSMUSG00000070709
drosophila_melanogaster	CG18476	FBGN0037931
drosophila_melanogaster	CG10669	FBGN0039329

Paralogs (5): ZNF664 (ENSG00000179195), ZNF648 (ENSG00000179930), ZFP62 (ENSG00000196670), ZNF485 (ENSG00000198298), ZNF808 (ENSG00000198482)

Protein

Protein identifiers

Zinc finger protein 721 — Q8TF20 (reviewed: Q8TF20)

All UniProt accessions (4): B4E159, D6RGC2, E5RGH0, Q8TF20

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TF20-1	1	yes
Q8TF20-2	2

RefSeq proteins (1): NP_597731* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13465, PF13912

UniProt features (47 total): zinc finger region 30, sequence conflict 12, cross-link 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF20-F1	71.42	0.00

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 (3): 478, 649, 786

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 91 (showing top): chr4p16, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, NUYTTEN_EZH2_TARGETS_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, HORIUCHI_WTAP_TARGETS_UP, JOHNSTONE_PARVB_TARGETS_3_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_UP, FORTSCHEGGER_PHF8_TARGETS_UP, ZWANG_DOWN_BY_2ND_EGF_PULSE, SRC_UP.V1_DN, JAK2_DN.V1_DN, ASH1L_TARGET_GENES, CEBPZ_TARGET_GENES, CHAF1B_TARGET_GENES, CREB3L4_TARGET_GENES

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): DNA binding (GO:0003677), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nuclear lumen (GO:0031981)

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
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF721	PIGG	Q5H8A4	506
ZNF721	OR5T1	Q8NG75	446
ZNF721	ZC2HC1C	Q53FD0	417
ZNF721	ZBTB21	Q9ULJ3	383
ZNF721	MS4A15	Q8N5U1	376
ZNF721	OR2W1	Q9Y3N9	358
ZNF721	HAUS2	Q9NVX0	350
ZNF721	PRR11	Q96HE9	349
ZNF721	VWA3A	A6NCI4	349
ZNF721	ZNF608	Q9ULD9	343
ZNF721	ZZZ3	Q8IYH5	331
ZNF721	NICOL1	Q5BLP8	326
ZNF721	MIER2	Q8N344	324
ZNF721	SLC49A3	Q6UXD7	314
ZNF721	CCDC7	Q96M83	312

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
ZNF721	PLEC	psi-mi:“MI:0915”(physical association)	0.400
ZNF721	TPR	psi-mi:“MI:0915”(physical association)	0.400
KLF8		psi-mi:“MI:0914”(association)	0.350
ZNF467	ZNF320	psi-mi:“MI:0914”(association)	0.350
FMR1	ZNF721	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): ZNF721 (Affinity Capture-MS), ZNF721 (Affinity Capture-RNA), ZNF721 (Affinity Capture-RNA), ZNF721 (Proximity Label-MS), ZNF721 (Proximity Label-MS), ZNF721 (Affinity Capture-MS), ZNF721 (Affinity Capture-MS), ZNF721 (Affinity Capture-MS), ZNF721 (Cross-Linking-MS (XL-MS)), ZNF721 (Affinity Capture-MS), ZNF721 (Affinity Capture-RNA)

ESM2 similar proteins: A2VDQ7, A6NK75, A6NN14, A6NNF4, A8MQ14, A8MTY0, A8MXY4, B7Z6K7, E9QAG8, O43345, O75290, O75373, O75437, P0CJ79, P10751, P17017, P17019, P17035, P17038, P18749, P35789, P51522, Q03923, Q03938, Q05481, Q14585, Q3SYV7, Q4V348, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6P5C7, Q6ZN08, Q6ZN57, Q6ZR52, Q86V71, Q86XN6, Q8IYB9, Q8N7Q3

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — NPC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	170
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

990 predictions. Top by Δscore:

Variant	Effect	Δscore
4:444428:CATAG:C	acceptor_gain	1.0000
4:444430:TAG:T	acceptor_gain	1.0000
4:444433:C:CC	acceptor_gain	1.0000
4:472569:CCTCA:C	donor_loss	1.0000
4:472570:CTCA:C	donor_loss	1.0000
4:472571:TCA:T	donor_loss	1.0000
4:472572:CA:C	donor_loss	1.0000
4:472574:C:A	donor_loss	1.0000
4:444429:ATAG:A	acceptor_gain	0.9900
4:444431:AGCTG:A	acceptor_loss	0.9900
4:444432:GC:G	acceptor_loss	0.9900
4:444433:CT:C	acceptor_loss	0.9900
4:444434:T:A	acceptor_loss	0.9900
4:497215:C:T	acceptor_gain	0.9900
4:499053:TACCT:T	donor_loss	0.9900
4:499054:A:C	donor_loss	0.9900
4:499055:C:A	donor_loss	0.9900
4:447593:TGC:T	donor_gain	0.9800
4:472702:C:G	acceptor_loss	0.9800
4:472703:T:C	acceptor_loss	0.9800
4:499055:CCTCG:C	donor_gain	0.9800
4:444431:AG:A	acceptor_gain	0.9700
4:467615:A:AC	donor_gain	0.9700
4:467616:C:CC	donor_gain	0.9700
4:497213:C:G	acceptor_gain	0.9700
4:497215:C:CT	acceptor_gain	0.9700
4:497216:A:T	acceptor_gain	0.9700
4:499054:A:AC	donor_gain	0.9700
4:499055:C:CC	donor_gain	0.9700
4:468893:A:AC	donor_gain	0.9600

AlphaMissense

6141 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:443525:A:C	F302L	0.990
4:443525:A:T	F302L	0.990
4:443527:A:G	F302L	0.990
4:441929:A:C	F834L	0.987
4:441929:A:T	F834L	0.987
4:441931:A:G	F834L	0.987
4:443609:A:C	F274L	0.987
4:443609:A:T	F274L	0.987
4:443611:A:G	F274L	0.987
4:441761:A:C	F890L	0.985
4:441761:A:T	F890L	0.985
4:441763:A:G	F890L	0.985
4:441845:A:C	F862L	0.985
4:441845:A:T	F862L	0.985
4:441847:A:G	F862L	0.985
4:443441:A:C	F330L	0.985
4:443441:A:T	F330L	0.985
4:443443:A:G	F330L	0.985
4:442853:A:C	F526L	0.982
4:442853:A:T	F526L	0.982
4:442855:A:G	F526L	0.982
4:442013:A:C	F806L	0.978
4:442013:A:T	F806L	0.978
4:442015:A:G	F806L	0.978
4:442769:A:C	F554L	0.977
4:442769:A:T	F554L	0.977
4:442771:A:G	F554L	0.977
4:442685:A:C	F582L	0.974
4:442685:A:T	F582L	0.974
4:442687:A:G	F582L	0.974

dbSNP variants (sampled 300 via entrez): RS1000031559 (4:498967 G>A,C), RS1000087470 (4:450639 T>C), RS10001047 (4:485832 A>C,G,T), RS1000210678 (4:474245 G>A,C), RS1000216685 (4:444572 G>T), RS1000262605 (4:492131 C>A,T), RS1000366332 (4:461917 G>A), RS1000495102 (4:470896 A>C,G), RS1000555030 (4:477303 T>C), RS1000605071 (4:450796 G>C), RS1000622830 (4:465838 G>A), RS1000913442 (4:454674 T>C), RS1000973216 (4:460738 T>C,G), RS10010103 (4:478450 G>C), RS1001034636 (4:497039 G>A)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	3
Arsenic	decreases expression, increases abundance, affects methylation	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	affects cotreatment, increases expression	1
lead acetate	affects cotreatment, increases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc protoporphyrin	affects cotreatment, increases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
cobalt oxide	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Clorgyline	increases expression	1

Clinical trials (associated diseases)

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