ZNF334

Summary

ZNF334 (zinc finger protein 334, HGNC:15806) is a protein-coding gene on chromosome 20q13.12, encoding Zinc finger protein 334 (Q9HCZ1). May be involved in transcriptional regulation.

This gene encodes a member of the C2H2 zinc finger family. The encoded protein contains a Krueppel-associated box, fourteen C2H2 zinc finger domains, and four C2H2-type/integrase DNA-binding domains. Decreased expression of this gene may be a marker for rheumatoid arthritis. Alternative splicing results in multiple transcript variants that encode different protein isoforms.

Source: NCBI Gene 55713 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 104 total
• MANE Select transcript: NM_001353824

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15806
Approved symbol	ZNF334
Name	zinc finger protein 334
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	bA179N14.1
Ensembl gene	ENSG00000198185
Ensembl biotype	protein_coding
OMIM	621017
Entrez	55713

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000347606, ENST00000457685, ENST00000593880, ENST00000596323, ENST00000615481, ENST00000625284, ENST00000692313, ENST00000866037, ENST00000938191, ENST00000938192, ENST00000938193, ENST00000938194, ENST00000938195, ENST00000956782

RefSeq mRNA: 17 — MANE Select: NM_001353824 NM_001270497, NM_001353813, NM_001353814, NM_001353815, NM_001353816, NM_001353817, NM_001353818, NM_001353819, NM_001353820, NM_001353821, NM_001353822, NM_001353823, NM_001353824, NM_001353825, NM_001353826, NM_018102, NM_199441

CCDS: CCDS33480, CCDS74736, CCDS86959

Canonical transcript exons

ENST00000692313 — 5 exons

Exon	Start	End
ENSE00000662663	46504214	46504306
ENSE00001524760	46512540	46513559
ENSE00003466601	46512082	46512140
ENSE00003488108	46504614	46504740
ENSE00003723903	46499630	46503097

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 91.21.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8884 / max 91.6704, expressed in 814 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187570	2.8884	814

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	91.21	gold quality
endothelial cell	CL:0000115	89.72	gold quality
ventricular zone	UBERON:0003053	87.47	gold quality
ganglionic eminence	UBERON:0004023	85.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.94	gold quality
cerebellar hemisphere	UBERON:0002245	85.61	gold quality
cerebellar cortex	UBERON:0002129	85.49	gold quality
adenohypophysis	UBERON:0002196	84.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.76	gold quality
left ovary	UBERON:0002119	84.73	gold quality
right ovary	UBERON:0002118	83.15	gold quality
cerebellum	UBERON:0002037	83.13	gold quality
pituitary gland	UBERON:0000007	82.89	gold quality
adrenal tissue	UBERON:0018303	82.73	gold quality
cortical plate	UBERON:0005343	82.72	gold quality
right lobe of thyroid gland	UBERON:0001119	82.12	gold quality
left lobe of thyroid gland	UBERON:0001120	82.00	gold quality
thyroid gland	UBERON:0002046	81.48	gold quality
body of pancreas	UBERON:0001150	81.39	gold quality
ovary	UBERON:0000992	81.34	gold quality
right adrenal gland cortex	UBERON:0035827	81.17	gold quality
right adrenal gland	UBERON:0001233	80.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.73	gold quality
left adrenal gland	UBERON:0001234	79.47	gold quality
right frontal lobe	UBERON:0002810	79.43	gold quality
left adrenal gland cortex	UBERON:0035825	79.13	gold quality
metanephros cortex	UBERON:0010533	78.65	gold quality
anterior cingulate cortex	UBERON:0009835	78.14	gold quality
cingulate cortex	UBERON:0003027	78.04	gold quality
nucleus accumbens	UBERON:0001882	77.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75367	no	62.85
E-ANND-3	no	5.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting ZNF334, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-548M	99.70	68.87	1749

Literature-anchored findings (GeneRIF, showing 4)

• results obtained in vitro for helper lymphocytes of healthy individuals seem to mimic the regulatory effect of TNFalpha on the expression of ZNF334 in the cells of RA patients (PMID:25738173)
• Disruption of ZNF334 promotes triple-negative breast carcinoma malignancy through the SFRP1/ Wnt/beta-catenin signaling axis. (PMID:35507080)
• DNA hypermethylation modification promotes the development of hepatocellular carcinoma by depressing the tumor suppressor gene ZNF334. (PMID:35534462)
• Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth. (PMID:36966142)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp334	ENSMUSG00000017667
rattus_norvegicus	Zfp334	ENSRNOG00000019099

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 334 — Q9HCZ1 (reviewed: Q9HCZ1)

All UniProt accessions (5): A0A087X1P4, A0A0B4J1Y0, Q9HCZ1, M0R3E1, Q8N3P8

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 (17): NP_001257426, NP_001340742, NP_001340743, NP_001340744, NP_001340745, NP_001340746, NP_001340747, NP_001340748, NP_001340749, NP_001340750, NP_001340751, NP_001340752, NP_001340753, NP_001340754, NP_001340755, NP_060572, NP_955473 (=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, PF13912

UniProt features (19 total): zinc finger region 14, sequence conflict 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCZ1-F1	63.54	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 77 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, TGCGCANK_UNKNOWN, DBP_Q6, NUYTTEN_EZH2_TARGETS_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, LIM_MAMMARY_STEM_CELL_DN, MYC_UP.V1_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ZNF362_TARGET_GENES, ZSCAN31_TARGET_GENES, MIR548AJ_3P_MIR548X_3P, MIR3121_3P, GSE10094_LCMV_VS_LISTERIA_IND_EFF_CD4_TCELL_DN, MIR8068

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

GO Molecular Function (6): 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), DNA binding (GO:0003677), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
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
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
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF334	TMEM220	Q6QAJ8	400
ZNF334	ELMO2	Q96JJ3	370
ZNF334	ABHD14A	Q9BUJ0	368
ZNF334	L3MBTL4	Q8NA19	326
ZNF334	ARHGAP28	Q9P2N2	317
ZNF334	GAL3ST1	Q99999	305
ZNF334	RPL39L	Q96EH5	300
ZNF334	RIC3	Q7Z5B4	290
ZNF334	NCOA5	Q9HCD5	274
ZNF334	EPHX3	Q9H6B9	273
ZNF334	SLC7A4	O43246	264
ZNF334	ADHFE1	Q8IWW8	260
ZNF334	SLC13A3	Q8WWT9	251
ZNF334	CTF1	Q16619	248
ZNF334	TINAGL1	Q9GZM7	246
ZNF334	FZD8	Q9H461	246

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CCNDBP1	ZNF334	psi-mi:“MI:0915”(physical association)	0.670
ZNF334	CDC37	psi-mi:“MI:0915”(physical association)	0.400
APP	ZNF334	psi-mi:“MI:0915”(physical association)	0.000
ZNF334	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): ZNF334 (Two-hybrid), ZNF334 (Two-hybrid), ZNF334 (Two-hybrid)

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

104 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

1168 predictions. Top by Δscore:

Variant	Effect	Δscore
20:46503095:TGT:T	acceptor_gain	1.0000
20:46503098:C:CC	acceptor_gain	1.0000
20:46504610:TTACC:T	donor_loss	1.0000
20:46504611:TA:T	donor_loss	1.0000
20:46504612:A:AC	donor_gain	1.0000
20:46504612:A:AG	donor_loss	1.0000
20:46504612:AC:A	donor_gain	1.0000
20:46504612:ACC:A	donor_gain	1.0000
20:46504613:C:CT	donor_gain	1.0000
20:46504613:CC:C	donor_gain	1.0000
20:46504613:CCC:C	donor_gain	1.0000
20:46504613:CCCA:C	donor_gain	1.0000
20:46504653:C:A	donor_gain	1.0000
20:46513454:T:TA	donor_gain	1.0000
20:46503094:ATGT:A	acceptor_gain	0.9900
20:46503095:TGTC:T	acceptor_loss	0.9900
20:46503096:GT:G	acceptor_gain	0.9900
20:46503097:TC:T	acceptor_loss	0.9900
20:46503098:CTA:C	acceptor_loss	0.9900
20:46503099:T:C	acceptor_loss	0.9900
20:46504209:CTTA:C	donor_loss	0.9900
20:46504210:TTA:T	donor_loss	0.9900
20:46504211:TACCT:T	donor_loss	0.9900
20:46504212:ACCT:A	donor_loss	0.9900
20:46504213:C:CT	donor_loss	0.9900
20:46504305:CC:C	acceptor_gain	0.9900
20:46504306:CC:C	acceptor_gain	0.9900
20:46504741:C:CC	acceptor_gain	0.9900
20:46504741:CTG:C	acceptor_loss	0.9900
20:46513414:C:A	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000037451 (20:46505732 A>G), RS1000072757 (20:46485330 A>C), RS1000128579 (20:46491627 C>G,T), RS1000159152 (20:46510944 C>G), RS1000211095 (20:46510716 C>T), RS1000214014 (20:46465102 A>C,G), RS1000223408 (20:46467926 T>C), RS1000238019 (20:46508878 T>C), RS1000263705 (20:46508552 A>G), RS1000269812 (20:46479187 T>C), RS1000329843 (20:46464937 T>C), RS1000383 (20:46464282 G>A,T), RS1000392114 (20:46505279 G>A), RS1000444416 (20:46514681 A>G), RS1000475931 (20:46490632 C>G)

Disease associations

OMIM: gene MIM:621017 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_29	Waist-to-hip ratio adjusted for BMI	4.000000e-10
GCST005957_10	Waist-to-hip ratio adjusted for BMI (age <50)	5.000000e-06
GCST005958_17	Waist-to-hip ratio adjusted for BMI (age >50)	3.000000e-06
GCST005962_25	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	decreases expression	2
methylmercuric chloride	decreases expression	1
geraniol	increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
arsenite	increases methylation	1
potassium chromate(VI)	decreases expression	1
ferrous chloride	decreases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Phenylmercuric Acetate	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Cadmium Chloride	increases expression, increases abundance	1

Clinical trials (associated diseases)

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