ZNF222

Summary

ZNF222 (zinc finger protein 222, HGNC:13015) is a protein-coding gene on chromosome 19q13.31, encoding Zinc finger protein 222 (Q9UK12). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 7673 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_001129996

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13015
Approved symbol	ZNF222
Name	zinc finger protein 222
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159885
Ensembl biotype	protein_coding
OMIM	617357
Entrez	7673

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000187879, ENST00000391960, ENST00000587846, ENST00000590160, ENST00000891278, ENST00000929482, ENST00000929483

RefSeq mRNA: 2 — MANE Select: NM_001129996 NM_001129996, NM_013360

CCDS: CCDS33045, CCDS46098

Canonical transcript exons

ENST00000391960 — 4 exons

Exon	Start	End
ENSE00002444011	44031817	44033110
ENSE00002882167	44025379	44025478
ENSE00003563107	44027398	44027490
ENSE00003594663	44027023	44027149

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 92.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.2640 / max 50.1673, expressed in 1584 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176241	4.2640	1584

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.28	gold quality
oocyte	CL:0000023	91.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.14	gold quality
cerebellar hemisphere	UBERON:0002245	78.22	gold quality
cerebellar cortex	UBERON:0002129	78.08	gold quality
cortical plate	UBERON:0005343	77.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.70	gold quality
apex of heart	UBERON:0002098	77.48	gold quality
cerebellum	UBERON:0002037	76.86	gold quality
ganglionic eminence	UBERON:0004023	76.09	gold quality
islet of Langerhans	UBERON:0000006	75.86	gold quality
adrenal tissue	UBERON:0018303	75.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.68	gold quality
stromal cell of endometrium	CL:0002255	75.36	gold quality
granulocyte	CL:0000094	75.24	gold quality
ventricular zone	UBERON:0003053	75.22	gold quality
left adrenal gland	UBERON:0001234	74.80	gold quality
right frontal lobe	UBERON:0002810	74.39	gold quality
adenohypophysis	UBERON:0002196	74.36	gold quality
left adrenal gland cortex	UBERON:0035825	74.15	gold quality
pituitary gland	UBERON:0000007	74.14	gold quality
right adrenal gland cortex	UBERON:0035827	74.12	gold quality
heart left ventricle	UBERON:0002084	73.97	gold quality
right adrenal gland	UBERON:0001233	73.88	gold quality
adrenal gland	UBERON:0002369	73.83	gold quality
cardiac ventricle	UBERON:0002082	73.63	gold quality
calcaneal tendon	UBERON:0003701	73.15	gold quality
descending thoracic aorta	UBERON:0002345	73.10	gold quality
prefrontal cortex	UBERON:0000451	73.03	gold quality
adrenal cortex	UBERON:0001235	72.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

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), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), 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 222 — Q9UK12 (reviewed: Q9UK12)

All UniProt accessions (2): Q9UK12, K7EN43

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?
Q9UK12-1	1	yes
Q9UK12-2	2

RefSeq proteins (2): NP_001123468, NP_037492 (=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 (18 total): zinc finger region 10, sequence variant 4, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK12-F1	65.79	0.02

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 39 (showing top): GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, NAGASHIMA_NRG1_SIGNALING_DN, CHEN_HOXA5_TARGETS_9HR_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, RELA_DN.V1_UP, OISHI_CHOLANGIOMA_STEM_CELL_LIKE_UP, STK33_NOMO_UP, STK33_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ZHONG_RESPONSE_TO_AZACITIDINE_AND_TSA_UP, TERF1_TARGET_GENES, ZNF175_TARGET_GENES

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

GO Molecular Function (5): DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), 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
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
DNA binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF222	TEX36	Q5VZQ5	510
ZNF222	PAFAH2	Q99487	506
ZNF222	GPR63	Q9BZJ6	474
ZNF222	JRKL	Q9Y4A0	402
ZNF222	LRRC46	Q96FV0	400
ZNF222	ADAMTS15	Q8TE58	377
ZNF222	FBXW12	Q6X9E4	376
ZNF222	NUDCD1	Q96RS6	370
ZNF222	CCDC134	Q9H6E4	368
ZNF222	IL11RA	Q14626	351
ZNF222	FSIP1	Q8NA03	348
ZNF222	EML2	O95834	348
ZNF222	USP43	Q70EL4	324
ZNF222	EXD3	Q8N9H8	311
ZNF222	WDR3	Q9UNX4	308

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ZNF222	PPM1G	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): ZNF222 (Cross-Linking-MS (XL-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

863 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44026087:G:GG	donor_gain	1.0000
19:44027133:G:GT	donor_gain	1.0000
19:44027146:G:GG	donor_gain	1.0000
19:44027146:GTGG:G	donor_gain	1.0000
19:44031050:T:G	donor_gain	1.0000
19:44025457:G:GT	donor_gain	0.9900
19:44025476:GAG:G	donor_gain	0.9900
19:44025518:C:G	donor_gain	0.9900
19:44027097:G:GT	donor_gain	0.9900
19:44027116:A:AG	donor_gain	0.9900
19:44027134:A:T	donor_gain	0.9900
19:44027145:AGTGG:A	donor_loss	0.9900
19:44027148:GG:G	donor_gain	0.9900
19:44027149:GG:G	donor_gain	0.9900
19:44027150:GT:G	donor_loss	0.9900
19:44027150:GTGA:G	donor_loss	0.9900
19:44027151:T:G	donor_loss	0.9900
19:44027155:G:GT	donor_gain	0.9900
19:44025470:A:T	donor_gain	0.9800
19:44025474:CAGAG:C	donor_loss	0.9800
19:44025475:AGAG:A	donor_loss	0.9800
19:44025475:AGAGG:A	donor_loss	0.9800
19:44025477:AG:A	donor_loss	0.9800
19:44025478:GGTTT:G	donor_loss	0.9800
19:44025479:G:A	donor_loss	0.9800
19:44025479:G:GC	donor_loss	0.9800
19:44025480:T:A	donor_loss	0.9800
19:44025558:G:GT	donor_gain	0.9800
19:44025687:T:A	acceptor_gain	0.9800
19:44027018:TGTA:T	acceptor_loss	0.9800

AlphaMissense

3305 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44032218:T:C	F182L	0.990
19:44032220:T:A	F182L	0.990
19:44032220:T:G	F182L	0.990
19:44032302:T:C	F210L	0.989
19:44032304:C:A	F210L	0.989
19:44032304:C:G	F210L	0.989
19:44027138:T:C	L44P	0.983
19:44032470:T:C	F266L	0.980
19:44032472:C:A	F266L	0.980
19:44032472:C:G	F266L	0.980
19:44027047:G:C	A14P	0.979
19:44032134:T:C	F154L	0.979
19:44032136:C:A	F154L	0.979
19:44032136:C:G	F154L	0.979
19:44032638:T:C	F322L	0.978
19:44032640:C:A	F322L	0.978
19:44032640:C:G	F322L	0.978
19:44032386:T:C	F238L	0.975
19:44032388:C:A	F238L	0.975
19:44032388:C:G	F238L	0.975
19:44032672:G:C	R333P	0.975
19:44027094:G:C	Q29H	0.973
19:44027094:G:T	Q29H	0.973
19:44027057:T:C	F17S	0.971
19:44027056:T:C	F17L	0.970
19:44027058:C:A	F17L	0.970
19:44027058:C:G	F17L	0.970
19:44027127:C:A	N40K	0.970
19:44027127:C:G	N40K	0.970
19:44027104:T:G	Y33D	0.969

dbSNP variants (sampled 300 via entrez): RS1000046543 (19:44026003 T>G), RS1000148116 (19:44032740 C>A,G), RS1000160503 (19:44026397 A>G), RS1000436516 (19:44032375 G>A,T), RS1001037153 (19:44030882 C>A,T), RS1001449636 (19:44028961 T>C), RS1002130447 (19:44028378 A>G), RS1002700141 (19:44033217 TGAG>T), RS1003126947 (19:44024506 C>T), RS1003222448 (19:44023716 A>T), RS1003319151 (19:44024053 G>A), RS1003377349 (19:44028753 G>A), RS1003878697 (19:44029888 C>T), RS1004211753 (19:44028343 T>C), RS1004711074 (19:44030279 T>C,G)

Disease associations

OMIM: gene MIM:617357 | 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

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
ferrous chloride	decreases expression	1
cupric oxide	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
NSC 689534	increases expression, affects binding	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects binding, increases expression	1
Drugs, Chinese Herbal	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Naphthoquinones	increases expression	1
Plant Oils	increases expression	1
Silver	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin M1	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1
Raloxifene Hydrochloride	increases expression	1

Clinical trials (associated diseases)

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