ZNF223

Summary

ZNF223 (zinc finger protein 223, HGNC:13016) is a protein-coding gene on chromosome 19q13.31, encoding Zinc finger protein 223 (Q9UK11). May be involved in transcriptional regulation.

This gene encodes a protein containing a Kruppel-associated box domain and multiple zinc finger domains. The function of this protein has yet to be determined.

Source: NCBI Gene 7766 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_013361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13016
Approved symbol	ZNF223
Name	zinc finger protein 223
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178386
Ensembl biotype	protein_coding
Entrez	7766

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000434772, ENST00000585552, ENST00000588518, ENST00000591850, ENST00000593088, ENST00000911408, ENST00000911409, ENST00000911410, ENST00000911411

RefSeq mRNA: 1 — MANE Select: NM_013361 NM_013361

CCDS: CCDS12635

Canonical transcript exons

ENST00000434772 — 5 exons

Exon	Start	End
ENSE00001636567	44066064	44067999
ENSE00001703080	44052036	44052195
ENSE00003552812	44055109	44055191
ENSE00003635912	44060455	44060581
ENSE00003662638	44060749	44060841

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 83.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5260 / max 108.5483, expressed in 1427 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176242	3.5260	1427

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	83.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.62	gold quality
cortical plate	UBERON:0005343	79.05	gold quality
rectum	UBERON:0001052	77.69	gold quality
lower esophagus mucosa	UBERON:0035834	77.32	gold quality
ganglionic eminence	UBERON:0004023	76.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.73	gold quality
adrenal tissue	UBERON:0018303	75.63	gold quality
right lung	UBERON:0002167	75.32	gold quality
stromal cell of endometrium	CL:0002255	74.89	gold quality
gall bladder	UBERON:0002110	74.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.72	gold quality
transverse colon	UBERON:0001157	74.57	gold quality
islet of Langerhans	UBERON:0000006	74.42	gold quality
left adrenal gland	UBERON:0001234	74.41	gold quality
right adrenal gland	UBERON:0001233	74.16	gold quality
right adrenal gland cortex	UBERON:0035827	74.13	gold quality
granulocyte	CL:0000094	74.06	gold quality
body of stomach	UBERON:0001161	73.77	gold quality
left adrenal gland cortex	UBERON:0035825	73.61	gold quality
left lobe of thyroid gland	UBERON:0001120	73.54	gold quality
ventricular zone	UBERON:0003053	73.50	gold quality
body of uterus	UBERON:0009853	73.47	gold quality
prefrontal cortex	UBERON:0000451	73.38	gold quality
cerebellar hemisphere	UBERON:0002245	73.31	gold quality
left uterine tube	UBERON:0001303	73.30	gold quality
minor salivary gland	UBERON:0001830	73.25	gold quality
cerebellar cortex	UBERON:0002129	73.20	gold quality
monocyte	CL:0000576	73.16	gold quality
right lobe of thyroid gland	UBERON:0001119	73.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting ZNF223, 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-1184	99.99	68.19	1458
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
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-548M	99.70	68.87	1749
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4311	99.31	70.47	3041

Cross-species orthologs

0 orthologs

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

Zinc finger protein 223 — Q9UK11 (reviewed: Q9UK11)

All UniProt accessions (4): Q9UK11, K7EPW2, K7EQ32, K7ER65

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.

RefSeq proteins (1): NP_037493* (*=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 (29 total): sequence conflict 15, zinc finger region 10, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK11-F1	64.44	0.13

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 43 (showing top): GOZGIT_ESR1_TARGETS_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, DIDO1_TARGET_GENES, SKIL_TARGET_GENES, SNAI1_TARGET_GENES, UBN1_TARGET_GENES, ZNF33A_TARGET_GENES, ZNF766_TARGET_GENES, ZNF8_TARGET_GENES, ZSCAN31_TARGET_GENES, GSE11057_CD4_EFF_MEM_VS_PBMC_UP, MIR3692_5P, MIR3140_5P

GO Biological Process (2): negative regulation of DNA-templated transcription (GO:0045892), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), 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
DNA-templated transcription	2
regulation of DNA-templated transcription	2
negative regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
DNA binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF223	ANKRD44	Q8N8A2	348
ZNF223	ASCC2	Q9H1I8	323
ZNF223	CDYL2	Q8N8U2	306
ZNF223	DOP1B	Q9Y3R5	305
ZNF223	TMT1B	Q6UX53	273
ZNF223	GNG13	Q9P2W3	269
ZNF223	GNG8	Q9UK08	256
ZNF223	SLC4A5	Q9BY07	252
ZNF223	GMPR	P36959	248
ZNF223	TRIM4	Q9C037	235
ZNF223	RFX2	P48378	224
ZNF223	MEX3C	Q5U5Q3	223
ZNF223	MKRN1	Q9UHC7	222
ZNF223	GNGT2	O14610	220
ZNF223	CLN8	Q9UBY8	217

IntAct

33 interactions, top by confidence:

A	B	Type	Score
ZNF223	MDFI	psi-mi:“MI:0915”(physical association)	0.780
MDFI	ZNF223	psi-mi:“MI:0915”(physical association)	0.780
KRTAP10-7	ZNF223	psi-mi:“MI:0915”(physical association)	0.670
ZNF223	ZC4H2	psi-mi:“MI:0915”(physical association)	0.670
ZNF223	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.670
ZC4H2	ZNF223	psi-mi:“MI:0915”(physical association)	0.670
CARD10	ZNF223	psi-mi:“MI:0915”(physical association)	0.560
CCNDBP1	ZNF223	psi-mi:“MI:0915”(physical association)	0.560
CABP5	ZNF223	psi-mi:“MI:0915”(physical association)	0.560
	ZNF223	psi-mi:“MI:0915”(physical association)	0.560
ZNF223	PPM1G	psi-mi:“MI:0914”(association)	0.530
ZNF223	CENPB	psi-mi:“MI:0914”(association)	0.530
ZNF223	FTH1	psi-mi:“MI:0914”(association)	0.350
NDEL1	ZNF223	psi-mi:“MI:0915”(physical association)	0.000
ZNF223	CARD10	psi-mi:“MI:0915”(physical association)	0.000
ZNF223	MDFI	psi-mi:“MI:0915”(physical association)	0.000
ZNF223		psi-mi:“MI:0915”(physical association)	0.000
ZNF223	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.000
CABP5	ZNF223	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (48): ZNF223 (Two-hybrid), ZC4H2 (Two-hybrid), KRTAP10-7 (Two-hybrid), ZNF223 (Two-hybrid), TRIM39 (Affinity Capture-MS), CENPB (Affinity Capture-MS), TRIM41 (Affinity Capture-MS), ZNF430 (Affinity Capture-MS), ZNF284 (Affinity Capture-MS), ZNF92 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), EHMT2 (Affinity Capture-MS), STRN4 (Affinity Capture-MS), HAUS4 (Affinity Capture-MS), ZNF714 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PQL4, A0JPL0, A2RRD8, A6NHJ4, A6NP11, B4DX44, O75346, O95780, P0CB33, P21506, P51508, P52738, Q0D2J5, Q0VGE8, Q12901, Q13360, Q14593, Q15973, Q2M218, Q2M3X9, Q2VY69, Q3SXZ3, Q5HY98, Q5RCJ2, Q5VIY5, Q6J6I6, Q7L2R6, Q86XU0, Q86Y25, Q8IW36, Q8IYN0, Q8IYX0, Q8N782, Q8N883, Q8N9Z0, Q8NDP4, Q95K49, Q969W8, Q96H40, Q96N58

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1190 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44052665:T:A	acceptor_gain	1.0000
19:44060743:TTACA:T	acceptor_loss	1.0000
19:44060744:TACA:T	acceptor_loss	1.0000
19:44060744:TACAG:T	acceptor_loss	1.0000
19:44060746:CA:C	acceptor_loss	1.0000
19:44060747:A:AG	acceptor_gain	1.0000
19:44060747:A:AT	acceptor_loss	1.0000
19:44060748:G:GG	acceptor_gain	1.0000
19:44060748:GGGC:G	acceptor_gain	1.0000
19:44052166:G:GT	donor_gain	0.9900
19:44052189:TTTAG:T	donor_gain	0.9900
19:44052193:GAG:G	donor_gain	0.9900
19:44052193:GAGGT:G	donor_loss	0.9900
19:44052194:AG:A	donor_loss	0.9900
19:44052195:GGTG:G	donor_loss	0.9900
19:44052196:G:T	donor_loss	0.9900
19:44052197:T:A	donor_loss	0.9900
19:44055095:AT:A	acceptor_gain	0.9900
19:44055095:ATG:A	acceptor_gain	0.9900
19:44055096:T:G	acceptor_gain	0.9900
19:44055096:T:TA	acceptor_gain	0.9900
19:44055097:G:A	acceptor_gain	0.9900
19:44060578:GTGG:G	donor_gain	0.9900
19:44060747:AG:A	acceptor_gain	0.9900
19:44060748:GG:G	acceptor_gain	0.9900
19:44060839:CAG:C	donor_loss	0.9900
19:44060839:CAGGT:C	donor_loss	0.9900
19:44060840:AG:A	donor_loss	0.9900
19:44060840:AGG:A	donor_loss	0.9900
19:44060841:GGT:G	donor_loss	0.9900

AlphaMissense

3234 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44066549:T:C	F241L	0.992
19:44066551:C:A	F241L	0.992
19:44066551:C:G	F241L	0.992
19:44066633:T:C	F269L	0.990
19:44066635:C:A	F269L	0.990
19:44066635:C:G	F269L	0.990
19:44066885:T:C	F353L	0.990
19:44066887:C:A	F353L	0.990
19:44066887:C:G	F353L	0.990
19:44066717:T:C	F297L	0.989
19:44066719:C:A	F297L	0.989
19:44066719:C:G	F297L	0.989
19:44066919:G:C	R364P	0.989
19:44066916:A:C	Q363P	0.987
19:44067053:T:C	F409L	0.985
19:44067055:T:A	F409L	0.985
19:44067055:T:G	F409L	0.985
19:44066465:T:C	F213L	0.979
19:44066467:C:A	F213L	0.979
19:44066467:C:G	F213L	0.979
19:44066904:T:C	L359P	0.979
19:44066912:C:G	H362D	0.978
19:44066690:T:C	F288L	0.977
19:44066692:C:A	F288L	0.977
19:44066692:C:G	F288L	0.977
19:44066926:C:A	H366Q	0.976
19:44066926:C:G	H366Q	0.976
19:44066988:T:C	L387P	0.976
19:44066914:T:A	H362Q	0.975
19:44066914:T:G	H362Q	0.975

dbSNP variants (sampled 300 via entrez): RS1000182776 (19:44054388 T>C), RS1000386562 (19:44064466 A>G), RS1000676684 (19:44064343 A>G), RS1000687877 (19:44051628 C>T), RS1001011218 (19:44051925 TC>T), RS1001044091 (19:44052181 A>G), RS1001213346 (19:44061106 C>T), RS1001330681 (19:44054271 C>T), RS1001901307 (19:44052696 A>G), RS1002084090 (19:44058816 G>C), RS1002118337 (19:44059189 C>T), RS1002228353 (19:44052632 G>A), RS1002518478 (19:44059057 G>A), RS1002730598 (19:44061632 C>G), RS1002757999 (19:44062364 A>G,T)

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

1 associations (top):

Study	Trait	p-value
GCST008887_7	Systemising	9.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010221	systemising measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ferrous chloride	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	increases expression, increases abundance	1
Cisplatin	increases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Phenylmercuric Acetate	decreases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XW22	HEK293 eGFP-ZNF223	Transformed cell line	Female

Clinical trials (associated diseases)

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