ZNF354B

Summary

ZNF354B (zinc finger protein 354B, HGNC:17197) is a protein-coding gene on chromosome 5q35.3, encoding Zinc finger protein 354B (Q96LW1). Transcriptional repressor that binds DNA upon activation by RAS proteins signal transduction to initiate transcriptional silencing through the recruitment of additional DNA-binding proteins, multisubunit complexes and chromatin-modifying activities to establish a platform for DN….

Predicted to enable several functions, including DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and transcription corepressor activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 117608 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_058230

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17197
Approved symbol	ZNF354B
Name	zinc finger protein 354B
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	KID2, FLJ25008
Ensembl gene	ENSG00000178338
Ensembl biotype	protein_coding
Entrez	117608

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000322434, ENST00000520377, ENST00000522624, ENST00000522714

RefSeq mRNA: 1 — MANE Select: NM_058230 NM_058230

CCDS: CCDS4439

Canonical transcript exons

ENST00000322434 — 5 exons

Exon	Start	End
ENSE00001263740	178859953	178860127
ENSE00001263754	178882709	178885020
ENSE00002451417	178860997	178861080
ENSE00002468403	178866244	178866370
ENSE00002491974	178866976	178867071

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 86.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5129 / max 151.2561, expressed in 1669 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60529	6.0316	1598
60530	0.8529	533
60531	0.6284	346

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	86.52	gold quality
body of pancreas	UBERON:0001150	86.41	gold quality
left lobe of thyroid gland	UBERON:0001120	86.13	gold quality
right lobe of thyroid gland	UBERON:0001119	86.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.99	gold quality
body of uterus	UBERON:0009853	85.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.76	gold quality
endocervix	UBERON:0000458	85.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.34	gold quality
lower esophagus	UBERON:0013473	85.33	gold quality
mucosa of stomach	UBERON:0001199	85.32	gold quality
right ovary	UBERON:0002118	85.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.97	gold quality
calcaneal tendon	UBERON:0003701	84.94	gold quality
cortical plate	UBERON:0005343	84.89	gold quality
thyroid gland	UBERON:0002046	84.75	gold quality
omental fat pad	UBERON:0010414	84.73	gold quality
left ovary	UBERON:0002119	84.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.64	gold quality
cerebellar hemisphere	UBERON:0002245	84.62	gold quality
peritoneum	UBERON:0002358	84.62	gold quality
ectocervix	UBERON:0012249	84.62	gold quality
right uterine tube	UBERON:0001302	84.52	gold quality
cerebellar cortex	UBERON:0002129	84.34	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.19	gold quality
lower esophagus mucosa	UBERON:0035834	83.87	gold quality
endothelial cell	CL:0000115	83.80	gold quality
tibial nerve	UBERON:0001323	83.77	gold quality
left coronary artery	UBERON:0001626	83.75	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.75	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	961.55
E-MTAB-7037	yes	285.43
E-GEOD-70580	yes	92.80
E-MTAB-9801	yes	5.50
E-ANND-3	no	2.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting ZNF354B, 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-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-630	97.50	66.38	921

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp354b	ENSMUSG00000020335
rattus_norvegicus	Znf454	ENSRNOG00000029678

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 354B — Q96LW1 (reviewed: Q96LW1)

All UniProt accessions (2): Q96LW1, E5RH89

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor that binds DNA upon activation by RAS proteins signal transduction to initiate transcriptional silencing through the recruitment of additional DNA-binding proteins, multisubunit complexes and chromatin-modifying activities to establish a platform for DNMT1 recruitment.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_478137* (*=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 (20 total): zinc finger region 13, region of interest 2, cross-link 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LW1-F1	67.48	0.13

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 (2): 150, 175

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 70 (showing top): WANG_CLIM2_TARGETS_UP, GOMF_CHROMATIN_BINDING, GAZIN_EPIGENETIC_SILENCING_BY_KRAS, HAMAI_APOPTOSIS_VIA_TRAIL_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY, MIKKELSEN_IPS_ICP_WITH_H3K4ME3_AND_H327ME3, MIKKELSEN_ES_ICP_WITH_H3K4ME3_AND_H3K27ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, TERAO_AOX4_TARGETS_SKIN_DN, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_TRANSCRIPTION_COREGULATOR_ACTIVITY, ZWANG_DOWN_BY_2ND_EGF_PULSE, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY

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

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), 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
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	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
binding	1
transcription coregulator activity	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF354B	SIMC1	Q8NDZ2	398
ZNF354B	WDR55	Q9H6Y2	370
ZNF354B	THG1L	Q9NWX6	367
ZNF354B	PCYOX1L	Q8NBM8	351
ZNF354B	RMND5B	Q96G75	349
ZNF354B	CYSTM1	Q9H1C7	348
ZNF354B	MED6	O75586	348
ZNF354B	GEMIN8	Q9NWZ8	333
ZNF354B	HIGD2A	Q9BW72	317
ZNF354B	UBLCP1	Q8WVY7	316
ZNF354B	SLC35A4	Q96G79	307
ZNF354B	DELE1	Q14154	305
ZNF354B	NMT2	O60551	301
ZNF354B	BCAS2	O75934	301
ZNF354B	NOP16	Q9Y3C1	298

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
MYC		psi-mi:“MI:0914”(association)	0.350
ADARB1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
hemL2	ZNF354B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): ZNF354B (Affinity Capture-RNA), ZNF354B (Affinity Capture-MS), ZNF354B (Affinity Capture-MS), ZNF354B (Affinity Capture-MS)

ESM2 similar proteins: A1L1L7, A3KN36, D3ZVT0, O43296, P08042, P13682, P16373, P17023, P17097, P52738, P85977, Q02975, Q12901, Q14590, Q14592, Q2M3W8, Q2VY69, Q4V8A8, Q571J5, Q5CZA5, Q5R7I8, Q5RB33, Q5RBX0, Q61751, Q61967, Q6GQR8, Q6PF04, Q6ZNG0, Q6ZS27, Q86Y25, Q8BFS8, Q8BQC8, Q8IZ26, Q8N782, Q8N9Z0, Q8R1D1, Q8TF47, Q8WTR7, Q96LW1, Q9BS31

Diamond homologs: A2A761, A2VDP4, A3KN32, A6QLU5, A6QPT6, A7MBI1, A8MT65, B4DU55, E9PYI1, O60765, O95780, P15622, P17014, P17032, P17098, P21506, P51508, P51814, P52736, P52738, P52742, Q02975, Q06730, Q06732, Q0VCB0, Q14587, Q16587, Q2KI58, Q2M3W8, Q3V080, Q49AA0, Q4R6C2, Q4V8A8, Q571J5, Q5HYK9, Q5JUW0, Q5JVG2, Q5MCW4, Q5MYW4, Q5R4K8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

736 predictions. Top by Δscore:

Variant	Effect	Δscore
5:178866238:TTACA:T	acceptor_loss	1.0000
5:178866239:TACA:T	acceptor_loss	1.0000
5:178866240:ACAGG:A	acceptor_loss	1.0000
5:178866241:CAGG:C	acceptor_loss	1.0000
5:178866242:A:T	acceptor_loss	1.0000
5:178866243:G:GA	acceptor_loss	1.0000
5:178866367:CTGGG:C	donor_loss	1.0000
5:178866369:GG:G	donor_gain	1.0000
5:178866369:GGGT:G	donor_loss	1.0000
5:178866370:GG:G	donor_gain	1.0000
5:178866370:GGTA:G	donor_loss	1.0000
5:178866371:G:GG	donor_gain	1.0000
5:178866371:G:T	donor_loss	1.0000
5:178866372:T:G	donor_loss	1.0000
5:178866969:T:G	acceptor_gain	1.0000
5:178866975:G:A	acceptor_loss	1.0000
5:178860591:G:T	donor_gain	0.9900
5:178861076:CCCAG:C	donor_loss	0.9900
5:178861077:CCAG:C	donor_loss	0.9900
5:178861078:CAGGT:C	donor_loss	0.9900
5:178861079:AG:A	donor_loss	0.9900
5:178861080:GGTGA:G	donor_loss	0.9900
5:178861081:G:GA	donor_loss	0.9900
5:178861082:T:A	donor_loss	0.9900
5:178866151:G:GT	donor_gain	0.9900
5:178866242:A:AG	acceptor_gain	0.9900
5:178866243:G:GG	acceptor_gain	0.9900
5:178866243:GGT:G	acceptor_gain	0.9900
5:178866367:CTGG:C	donor_gain	0.9900
5:178866968:A:AG	acceptor_gain	0.9900

AlphaMissense

4067 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:178883623:T:C	F391L	0.999
5:178883625:C:A	F391L	0.999
5:178883625:C:G	F391L	0.999
5:178883642:T:C	L397P	0.999
5:178883707:T:C	F419L	0.999
5:178883709:T:A	F419L	0.999
5:178883709:T:G	F419L	0.999
5:178883726:T:C	L425P	0.999
5:178883708:T:C	F419S	0.998
5:178883713:T:C	S421P	0.998
5:178883959:T:C	F503L	0.998
5:178883961:C:A	F503L	0.998
5:178883961:C:G	F503L	0.998
5:178883988:C:A	H512Q	0.998
5:178883988:C:G	H512Q	0.998
5:178883734:C:G	H428D	0.997
5:178883736:C:A	H428Q	0.997
5:178883736:C:G	H428Q	0.997
5:178883978:T:C	L509P	0.997
5:178883986:C:G	H512D	0.997
5:178884043:T:C	F531L	0.997
5:178884045:T:A	F531L	0.997
5:178884045:T:G	F531L	0.997
5:178883652:T:A	H400Q	0.996
5:178883652:T:G	H400Q	0.996
5:178883723:G:C	R424P	0.996
5:178883734:C:A	H428N	0.996
5:178883825:G:C	R458P	0.996
5:178883875:T:C	F475L	0.996
5:178883877:C:A	F475L	0.996

dbSNP variants (sampled 300 via entrez): RS1000006789 (5:178873694 T>TA), RS1000089818 (5:178864271 T>C), RS1000134128 (5:178860811 C>G,T), RS1000248736 (5:178880715 G>A), RS1000492876 (5:178869912 G>A,C), RS1000545371 (5:178870163 GAAAA>G,GAAA,GAAAAA,GAAAAAAAA), RS1000753051 (5:178860323 G>C,T), RS1000848244 (5:178880682 A>G), RS1000878284 (5:178876607 A>G), RS1000929785 (5:178870815 C>T), RS1001001823 (5:178871069 C>T), RS1001131510 (5:178864185 T>C), RS1001163136 (5:178876380 G>A), RS1001357667 (5:178879727 T>G), RS1001550657 (5:178874152 T>A,G)

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

4 associations (top):

Study	Trait	p-value
GCST007676_10	3-month functional outcome in ischaemic stroke (modified Rankin score)	2.000000e-06
GCST009305_17	California verbal learning test score	3.000000e-06
GCST009310_6	Sensorimotor dexterity	3.000000e-06
GCST010002_45	Refractive error	9.000000e-17

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement
EFO:0004874	memory performance
EFO:0008354	cognitive function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arbutin	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Phenobarbital	affects expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XW96	K562 eGFP-ZNF354B	Cancer cell line	Female

Clinical trials (associated diseases)

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