ZNF658

Summary

ZNF658 (zinc finger protein 658, HGNC:25226) is a protein-coding gene on chromosome 9q21.11, encoding Zinc finger protein 658 (Q5TYW1). Mediates transcriptional repression in response to zinc. It is a selective cancer dependency (DepMap: 23.3% of cell lines).

Enables transcription cis-regulatory region binding activity. Involved in cellular response to zinc ion; negative regulation of DNA-templated transcription; and ribosome biogenesis. Predicted to be active in nucleus.

Source: NCBI Gene 26149 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 200 total
• Cancer dependency (DepMap): dependent in 23.3% of screened cell lines
• MANE Select transcript: NM_033160

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25226
Approved symbol	ZNF658
Name	zinc finger protein 658
Location	9q21.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC35232, DKFZp572C163, FLJ32813
Ensembl gene	ENSG00000274349
Ensembl biotype	protein_coding
OMIM	616290
Entrez	26149

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000612867, ENST00000616544, ENST00000619435, ENST00000619925, ENST00000621015, ENST00000621410, ENST00000622180, ENST00000851907, ENST00000967696, ENST00000967697

RefSeq mRNA: 2 — MANE Select: NM_033160 NM_001317916, NM_033160

CCDS: CCDS75846

Canonical transcript exons

ENST00000621410 — 5 exons

Exon	Start	End
ENSE00003712830	66900725	66900836
ENSE00003721129	66908238	66908364
ENSE00003729860	66903518	66903576
ENSE00003734161	66917805	66921426
ENSE00003784188	66908639	66908734

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 83.97.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	83.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.88	gold quality
corpus callosum	UBERON:0002336	75.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.57	gold quality
cortical plate	UBERON:0005343	75.38	gold quality
islet of Langerhans	UBERON:0000006	74.96	gold quality
skeletal muscle tissue	UBERON:0001134	74.80	gold quality
ventricular zone	UBERON:0003053	74.06	gold quality
muscle tissue	UBERON:0002385	73.51	gold quality
endometrium	UBERON:0001295	73.13	gold quality
muscle of leg	UBERON:0001383	73.08	gold quality
heart left ventricle	UBERON:0002084	72.45	gold quality
zone of skin	UBERON:0000014	72.44	gold quality
gastrocnemius	UBERON:0001388	72.40	gold quality
skin of leg	UBERON:0001511	72.38	gold quality
skin of abdomen	UBERON:0001416	72.26	gold quality
smooth muscle tissue	UBERON:0001135	72.24	gold quality
ganglionic eminence	UBERON:0004023	71.89	gold quality
heart	UBERON:0000948	71.73	gold quality
urinary bladder	UBERON:0001255	71.44	gold quality
right atrium auricular region	UBERON:0006631	71.02	gold quality
pancreas	UBERON:0001264	70.79	gold quality
tonsil	UBERON:0002372	70.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.32	gold quality
lower esophagus	UBERON:0013473	70.31	gold quality
right adrenal gland cortex	UBERON:0035827	70.16	gold quality
right adrenal gland	UBERON:0001233	70.08	gold quality
apex of heart	UBERON:0002098	69.97	gold quality
ovary	UBERON:0000992	69.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting ZNF658, 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-4282	99.99	75.36	6408
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-548AR-3P	99.85	71.26	3889
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-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-3920	97.75	69.02	1168
HSA-MIR-27B-5P	97.34	66.55	549
HSA-MIR-10397-5P	97.31	69.06	710
HSA-MIR-6892-5P	97.27	68.60	847

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Genomic Characterization of the Zinc Transcriptional Regulatory Element Reveals Potential Functional Roles of ZNF658 (PMID:30734197)

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), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger protein 658 — Q5TYW1 (reviewed: Q5TYW1)

All UniProt accessions (5): Q5TYW1, A0A087WVA2, A0A087WZ36, A0A087X0H1, A0A087X186

UniProt curated annotations — full annotation on UniProt →

Function. Mediates transcriptional repression in response to zinc. Represses several genes, including SLC30A5, SLC30A10 and CBWD1, by binding to the zinc transcriptional regulatory element (ZTRE) (5’-C[AC]C[TAG]CC[TC]-N(0-50)-[GA]G[ATC]G[TG]G-3’) found in the promoter region. May play a role in the control of ribosome biogenesis, regulating predominantly rRNA levels, as well as those of several ribosomal proteins, thus coordinating this highly zinc-demanding process with the available zinc supply.

Subcellular location. Nucleus.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TYW1-1	1	yes
Q5TYW1-2	2

RefSeq proteins (2): NP_001304845, NP_149350* (*=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
IPR050826	Krueppel_C2H2_ZnFinger	Family

Pfam: PF00096, PF01352

UniProt features (30 total): zinc finger region 24, splice variant 2, chain 1, domain 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TYW1-F1	60.24	0.03

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 (1): 178

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 41 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_RESPONSE_TO_ZINC_ION, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_RESPONSE_TO_METAL_ION, GHO_ATF5_TARGETS_UP, GOBP_CELLULAR_RESPONSE_TO_ZINC_ION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, chr9q21, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ZWANG_DOWN_BY_2ND_EGF_PULSE, MIR548AR_3P, MIR548F_3P, MIR548BC

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), ribosome biogenesis (GO:0042254), negative regulation of DNA-templated transcription (GO:0045892), cellular response to zinc ion (GO:0071294), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): transcription cis-regulatory region binding (GO:0000976), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

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 DNA-templated transcription	2
DNA-templated transcription	2
transcription by RNA polymerase II	1
ribonucleoprotein complex biogenesis	1
negative regulation of RNA biosynthetic process	1
response to zinc ion	1
cellular response to metal ion	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF658	GOLGA6L7	A0A1B0GV03	621
ZNF658	OR5J2	Q8NH18	574
ZNF658	C2orf81	A6NN90	433
ZNF658	CHD8	Q9HCK8	433
ZNF658	SLC30A5	Q8TAD4	421
ZNF658	CCDC154	A6NI56	400
ZNF658	KIAA0319L	Q8IZA0	396
ZNF658	EPB41L4A	Q9HCS5	395
ZNF658	LRRC3C	A6NJW4	394
ZNF658	GALNTL5	Q7Z4T8	394
ZNF658	SGCZ	Q96LD1	390
ZNF658	STMP1	E0CX11	390
ZNF658	TLK2	Q86UE8	381
ZNF658	TLK1	Q9UKI8	376
ZNF658	IQCN	Q9H0B3	370

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
ZNF658	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ZNF658	DNAJB5	psi-mi:“MI:0914”(association)	0.350
GOLGA2	MYO1C	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (13): ZNF658 (Affinity Capture-MS), ZNF658 (Affinity Capture-MS), ZNF658 (Proximity Label-MS), TRIM28 (Affinity Capture-MS), DNAJB5 (Affinity Capture-MS), TRIM39 (Affinity Capture-MS), NDOR1 (Affinity Capture-MS), ZNF658 (Affinity Capture-MS), ZNF658 (Affinity Capture-MS), ZNF658 (Affinity Capture-MS), ZNF658 (Cross-Linking-MS (XL-MS)), ZNF658 (Affinity Capture-RNA), ZNF658 (Affinity Capture-MS)

ESM2 similar proteins: A2VDP4, A6NHJ4, O94892, P0CJ79, P17014, P17021, P17025, P17032, P17035, P18733, P51508, P51814, Q06730, Q06732, Q09FC8, Q0VGE8, Q14586, Q32M78, Q3MIS6, Q5JVG2, Q5R4K8, Q5R9S5, Q5RBQ3, Q5RCJ2, Q5RER9, Q5TYW1, Q5VIY5, Q6P560, Q6PDB4, Q6ZMW2, Q6ZN06, Q6ZNA1, Q76KX8, Q7L2R6, Q86Y25, Q8N184, Q8N823, Q8N883, Q8N8J6, Q8NEP9

Diamond homologs: A0JPL0, A2VDP4, A6QLU5, A6QPT6, A8MQ14, A8MUZ8, A8MWA4, B1APH4, B2RXC5, E9PYI1, E9Q8G5, O75290, O94892, P08042, P0CH99, P0CI00, P17014, P17025, P17030, P17031, P17032, P17098, P21506, P51508, P51523, P51786, P51814, P52736, P52738, Q02525, Q03923, Q03936, Q06730, Q06732, Q0VCB0, Q13401, Q14587, Q16587, Q2M218, Q2M3X9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	182
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

800 predictions. Top by Δscore:

Variant	Effect	Δscore
9:66908359:C:CC	donor_gain	1.0000
9:66908360:A:AC	donor_gain	1.0000
9:66908363:C:CC	donor_gain	1.0000
9:66908363:CC:C	donor_gain	1.0000
9:66908363:CCC:C	donor_gain	1.0000
9:66908363:CCCA:C	donor_gain	1.0000
9:66908364:A:AC	donor_gain	1.0000
9:66908364:A:C	donor_loss	1.0000
9:66908364:AC:A	donor_gain	1.0000
9:66908364:ACC:A	donor_gain	1.0000
9:66908365:CA:C	donor_loss	1.0000
9:66908366:TCA:T	donor_loss	1.0000
9:66908367:CTCA:C	donor_loss	1.0000
9:66908368:GCTCA:G	donor_loss	1.0000
9:66908637:CC:C	acceptor_gain	1.0000
9:66908638:TC:T	acceptor_gain	1.0000
9:66908638:TCC:T	acceptor_loss	1.0000
9:66908640:TATC:T	acceptor_gain	1.0000
9:66908733:C:T	donor_loss	1.0000
9:66908736:TCA:T	donor_loss	1.0000
9:66900935:T:TA	donor_gain	0.9900
9:66903024:AG:A	donor_gain	0.9900
9:66903515:C:CC	acceptor_gain	0.9900
9:66908226:CATT:C	acceptor_gain	0.9900
9:66908234:T:G	acceptor_loss	0.9900
9:66908235:C:CC	acceptor_gain	0.9900
9:66908636:C:CC	acceptor_gain	0.9900
9:66908733:C:CC	donor_gain	0.9900
9:66908734:A:AC	donor_gain	0.9900
9:66917803:CC:C	acceptor_gain	0.9900

AlphaMissense

7092 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:66920069:T:C	F835L	0.997
9:66920071:C:A	F835L	0.997
9:66920071:C:G	F835L	0.997
9:66919313:T:C	F583L	0.996
9:66919315:T:A	F583L	0.996
9:66919315:T:G	F583L	0.996
9:66919901:T:C	F779L	0.996
9:66919903:C:A	F779L	0.996
9:66919903:C:G	F779L	0.996
9:66920153:T:C	F863L	0.996
9:66920155:T:A	F863L	0.996
9:66920155:T:G	F863L	0.996
9:66920573:T:C	F1003L	0.996
9:66920575:T:A	F1003L	0.996
9:66920575:T:G	F1003L	0.996
9:66919565:T:C	F667L	0.995
9:66919567:C:A	F667L	0.995
9:66919567:C:G	F667L	0.995
9:66919985:T:C	F807L	0.995
9:66919987:T:A	F807L	0.995
9:66919987:T:G	F807L	0.995
9:66919229:T:C	F555L	0.994
9:66919231:C:A	F555L	0.994
9:66919231:C:G	F555L	0.994
9:66919733:T:C	F723L	0.994
9:66919735:T:A	F723L	0.994
9:66919735:T:G	F723L	0.994
9:66919649:T:C	F695L	0.993
9:66919651:T:A	F695L	0.993
9:66919651:T:G	F695L	0.993

dbSNP variants (sampled 300 via entrez): RS1000002444 (9:66900679 C>G,T), RS1000141849 (9:66905299 C>A), RS1000217611 (9:66922428 T>G), RS1000422865 (9:66916213 C>A,T), RS1000515112 (9:66905640 C>T), RS1000597866 (9:66901867 C>T), RS1000703422 (9:66928887 T>C,G), RS1000717666 (9:66929111 C>T), RS1000752969 (9:66916670 T>A,C), RS1000837082 (9:66911928 G>A,T), RS1001003064 (9:66901514 T>C), RS1001115214 (9:66906905 C>T), RS1001211484 (9:66906290 G>A), RS1001364507 (9:66901175 T>A,C,G), RS1001395621 (9:66901020 G>C)

Disease associations

OMIM: gene MIM:616290 | 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

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
avobenzone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Glyphosate	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Estradiol	affects expression	1
Formaldehyde	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Potassium Chloride	decreases response to substance, decreases expression	1
Dronabinol	decreases expression, decreases response to substance	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases 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_XW73	HEK293 eGFP-ZNF658	Transformed cell line	Female

Clinical trials (associated diseases)

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