ZNF221

Summary

ZNF221 (zinc finger protein 221, HGNC:13014) is a protein-coding gene on chromosome 19q13.31, encoding Zinc finger protein 221 (Q9UK13). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 7638 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 102 total
• MANE Select transcript: NM_001297588

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13014
Approved symbol	ZNF221
Name	zinc finger protein 221
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159905
Ensembl biotype	protein_coding
Entrez	7638

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000251269, ENST00000587682, ENST00000591168, ENST00000592350, ENST00000622072, ENST00000886290

RefSeq mRNA: 3 — MANE Select: NM_001297588 NM_001297588, NM_001297589, NM_013359

CCDS: CCDS12633

Canonical transcript exons

ENST00000587682 — 5 exons

Exon	Start	End
ENSE00000847471	43962725	43962807
ENSE00002532872	43965233	43965325
ENSE00002707868	43964950	43965076
ENSE00002799284	43965804	43967709
ENSE00002878009	43951228	43951400

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 82.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.3283 / max 172.2434, expressed in 1170 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176237	3.3283	1170

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.03	gold quality
buccal mucosa cell	CL:0002336	80.44	silver quality
calcaneal tendon	UBERON:0003701	79.58	gold quality
tendon	UBERON:0000043	76.94	gold quality
stromal cell of endometrium	CL:0002255	75.22	gold quality
cortical plate	UBERON:0005343	74.53	gold quality
tendon of biceps brachii	UBERON:0008188	73.37	gold quality
hair follicle	UBERON:0002073	72.81	gold quality
adrenal tissue	UBERON:0018303	71.26	gold quality
corpus callosum	UBERON:0002336	71.23	gold quality
ventricular zone	UBERON:0003053	71.08	gold quality
medial globus pallidus	UBERON:0002477	70.39	gold quality
sural nerve	UBERON:0015488	70.03	gold quality
ganglionic eminence	UBERON:0004023	68.68	gold quality
globus pallidus	UBERON:0001875	67.99	gold quality
smooth muscle tissue	UBERON:0001135	66.88	gold quality
islet of Langerhans	UBERON:0000006	66.73	gold quality
cerebellar cortex	UBERON:0002129	64.40	gold quality
cerebellar hemisphere	UBERON:0002245	64.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	64.23	gold quality
cerebellum	UBERON:0002037	63.97	gold quality
parotid gland	UBERON:0001831	63.90	gold quality
colonic epithelium	UBERON:0000397	63.47	silver quality
adrenal gland	UBERON:0002369	63.32	gold quality
bone marrow cell	CL:0002092	62.82	silver quality
left adrenal gland	UBERON:0001234	62.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.15	gold quality
left adrenal gland cortex	UBERON:0035825	61.85	gold quality
cerebellar vermis	UBERON:0004720	61.58	gold quality
right adrenal gland	UBERON:0001233	61.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7249	no	29.99
E-ANND-3	no	3.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting ZNF221, 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-188-3P	100.00	68.76	1240
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-4790-3P	96.63	67.08	806

Cross-species orthologs

0 orthologs

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), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631), ZNF3 (ENSG00000166526)

Protein

Protein identifiers

Zinc finger protein 221 — Q9UK13 (reviewed: Q9UK13)

All UniProt accessions (2): Q9UK13, A0A5H1ZRS7

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 (3): NP_001284517, NP_001284518, NP_037491 (=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 (24 total): zinc finger region 15, sequence variant 6, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK13-F1	70.39	0.08

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 61 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, NOTCH_DN.V1_DN, JAK2_DN.V1_DN, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CHAMP1_TARGET_GENES, DIDO1_TARGET_GENES, GLI4_TARGET_GENES, HES2_TARGET_GENES, RYBP_TARGET_GENES, ZNF197_TARGET_GENES, ZNF30_TARGET_GENES

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (2): nucleoplasm (GO:0005654), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF221	OR10J1	P30954	507
ZNF221	OR11A1	Q9GZK7	507
ZNF221	ZSWIM1	Q9BR11	478
ZNF221	PRDM10	Q9NQV6	431
ZNF221	CARD19	Q96LW7	418
ZNF221	C19orf53	Q9UNZ5	407
ZNF221	GPATCH4	Q5T3I0	404
ZNF221	SLC27A5	Q9Y2P5	387
ZNF221	CTCFL	Q8NI51	385
ZNF221	NECAB1	Q8N987	370
ZNF221	DUS2	Q9NX74	370
ZNF221	CEMP1	Q6PRD7	348
ZNF221	LHFPL6	Q9Y693	322
ZNF221	CRYBA2	P53672	312
ZNF221	KIAA1217	Q5T5P2	310

IntAct

12 interactions, top by confidence:

A	B	Type	Score
MAGEA8	ZNF221	psi-mi:“MI:0915”(physical association)	0.560
MDFI	ZNF221	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	ZNF221	psi-mi:“MI:0915”(physical association)	0.560
ZNF221	ZNF284	psi-mi:“MI:0914”(association)	0.530
ZNF221	CDK11B	psi-mi:“MI:0914”(association)	0.350
ZNF221	MAGEA8	psi-mi:“MI:0915”(physical association)	0.000
ZNF221	MDFI	psi-mi:“MI:0915”(physical association)	0.000
ZNF221	KRTAP10-6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): ZNF225 (Affinity Capture-MS), CDK11B (Affinity Capture-MS), ZNF284 (Affinity Capture-MS), ZNF221 (Affinity Capture-RNA), ZNF221 (Affinity Capture-MS), ZNF221 (Two-hybrid), ZNF221 (Two-hybrid), KRTAP10-6 (Two-hybrid), ZNF221 (Affinity Capture-RNA), ZNF225 (Affinity Capture-MS), ZNF284 (Affinity Capture-MS), ZNF221 (Affinity Capture-MS)

ESM2 similar proteins: A0JNB1, A1YF12, A1YG88, A2T759, A6QLU5, B2RUI1, D3ZVT0, O14709, O43296, O75123, P10072, P15621, P17020, P17097, P51814, P85977, Q08ER8, Q0VGE8, Q14590, Q32KN0, Q3KQV3, Q4V8A8, Q5CZA5, Q5RBX0, Q5RCD9, Q5VIY5, Q61116, Q61967, Q6GQR8, Q6P9A3, Q6ZMS4, Q7TSH9, Q7TSI0, Q7Z3I7, Q86UD4, Q86WZ6, Q8BFS8, Q8IZ26, Q8N9F8, Q8TAF7

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

590 predictions. Top by Δscore:

Variant	Effect	Δscore
19:43951375:A:T	donor_gain	1.0000
19:43951379:G:GT	donor_gain	1.0000
19:43951392:A:T	donor_gain	1.0000
19:43962703:T:TA	acceptor_gain	1.0000
19:43962712:T:TA	acceptor_gain	1.0000
19:43962713:G:A	acceptor_gain	1.0000
19:43962808:G:GG	donor_gain	1.0000
19:43964948:A:G	acceptor_loss	1.0000
19:43964949:G:GC	acceptor_loss	1.0000
19:43965073:GTAG:G	donor_gain	1.0000
19:43965231:A:AG	acceptor_gain	1.0000
19:43965231:AG:A	acceptor_gain	1.0000
19:43965232:G:GG	acceptor_gain	1.0000
19:43965232:GG:G	acceptor_gain	1.0000
19:43965323:CAGGT:C	donor_loss	1.0000
19:43965326:G:GA	donor_loss	1.0000
19:43965326:G:GG	donor_gain	1.0000
19:43965327:T:G	donor_loss	1.0000
19:43965800:TTAG:T	acceptor_loss	1.0000
19:43965802:A:AG	acceptor_gain	1.0000
19:43965802:A:T	acceptor_loss	1.0000
19:43965802:AGGAG:A	acceptor_gain	1.0000
19:43965803:G:GG	acceptor_gain	1.0000
19:43965803:G:GT	acceptor_loss	1.0000
19:43965803:GGA:G	acceptor_gain	1.0000
19:43965803:GGAGG:G	acceptor_gain	1.0000
19:43951409:GG:G	donor_gain	0.9900
19:43951410:GG:G	donor_gain	0.9900
19:43962716:A:AG	acceptor_gain	0.9900
19:43962724:GGC:G	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000167051 (19:43973625 G>A), RS1000280509 (19:43981695 C>T), RS1000377306 (19:43967411 A>G), RS1000509019 (19:43956823 CTG>C), RS1000530153 (19:43968547 C>G,T), RS1000533808 (19:43961224 G>T), RS1000699013 (19:43975682 C>G), RS1000708335 (19:43975996 A>G), RS1000964383 (19:43968865 C>A), RS1001313475 (19:43963939 A>G,T), RS1001536899 (19:43955307 GACAA>G), RS1001581088 (19:43951299 C>G,T), RS1001769144 (19:43957864 A>G), RS1002063079 (19:43975627 C>A), RS1002133240 (19:43963288 A>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
GCST010146_16	Serum immune biomarker levels	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases reaction, increases expression, increases abundance	3
Vehicle Emissions	decreases reaction, increases expression, increases abundance	2
TAK-243	increases sumoylation	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
Leflunomide	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	decreases expression	1
Acrylamide	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_XW21	HEK293 eGFP-ZNF221	Transformed cell line	Female

Clinical trials (associated diseases)

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