ZNF574

Summary

ZNF574 (zinc finger protein 574, HGNC:26166) is a protein-coding gene on chromosome 19q13.2, encoding Zinc finger protein 574 (Q6ZN55). Part of a ribosome quality control that mediates surveillance of ribosome assembly and promotes degradation of ribosomes with assembly defects. It is a selective cancer dependency (DepMap: 72.0% of cell lines).

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 64763 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 142 total
• Cancer dependency (DepMap): dependent in 72.0% of screened cell lines
• MANE Select transcript: NM_022752

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26166
Approved symbol	ZNF574
Name	zinc finger protein 574
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22059
Ensembl gene	ENSG00000105732
Ensembl biotype	protein_coding
Entrez	64763

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000222339, ENST00000359044, ENST00000597391, ENST00000600245, ENST00000852237, ENST00000933758, ENST00000933761

RefSeq mRNA: 2 — MANE Select: NM_022752 NM_001330519, NM_022752

CCDS: CCDS12596, CCDS82356

Canonical transcript exons

ENST00000359044 — 2 exons

Exon	Start	End
ENSE00001510305	42076166	42076286
ENSE00003046952	42078587	42081552

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 91.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2892 / max 87.0869, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176112	13.2892	1797

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	91.46	gold quality
olfactory bulb	UBERON:0002264	91.38	gold quality
cerebellar vermis	UBERON:0004720	89.84	gold quality
right testis	UBERON:0004534	89.29	gold quality
left testis	UBERON:0004533	89.09	gold quality
oocyte	CL:0000023	89.08	gold quality
vena cava	UBERON:0004087	89.06	gold quality
tongue squamous epithelium	UBERON:0006919	88.16	silver quality
parotid gland	UBERON:0001831	87.70	gold quality
testis	UBERON:0000473	87.28	gold quality
tendon of biceps brachii	UBERON:0008188	86.94	silver quality
lateral nuclear group of thalamus	UBERON:0002736	86.53	gold quality
cervix squamous epithelium	UBERON:0006922	86.14	silver quality
nipple	UBERON:0002030	85.68	gold quality
body of tongue	UBERON:0011876	85.60	gold quality
secondary oocyte	CL:0000655	85.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.51	gold quality
inferior olivary complex	UBERON:0002127	85.49	gold quality
nasal cavity epithelium	UBERON:0005384	85.31	gold quality
male germ cell	CL:0000015	85.22	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	85.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	84.74	gold quality
sperm	CL:0000019	84.47	gold quality
subthalamic nucleus	UBERON:0001906	84.47	gold quality
cardia of stomach	UBERON:0001162	84.32	silver quality
tongue	UBERON:0001723	84.07	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.07	gold quality
vastus lateralis	UBERON:0001379	83.58	silver quality
pharyngeal mucosa	UBERON:0000355	83.05	gold quality
heart right ventricle	UBERON:0002080	82.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.78

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1982.1	ZNF574	Factors with multiple dispersed zinc fingers
MA1982.2	ZNF574	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:22955616

miRNA regulators (miRDB)

18 targeting ZNF574, 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-153-5P	99.89	73.86	6317
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-3085-5P	97.72	65.43	544
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-6777-3P	95.35	64.30	699

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• ZNF574 Promotes Ovarian Cancer Cell Proliferation and Migration through Regulating AKT and AMPK Signaling Pathways. (PMID:36197766)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:66472	ENSDARG00000075916
mus_musculus	Zfp574	ENSMUSG00000045252
rattus_norvegicus	Zfp574	ENSRNOG00000055761
drosophila_melanogaster	mld	FBGN0263490

Paralogs (36): ZNF302 (ENSG00000089335), ZNF184 (ENSG00000096654), CTCF (ENSG00000102974), ZBTB24 (ENSG00000112365), ZNF142 (ENSG00000115568), CTCFL (ENSG00000124092), ZNF473 (ENSG00000142528), ZNF827 (ENSG00000151612), ZNF689 (ENSG00000156853), ZNF208 (ENSG00000160321), ZNF91 (ENSG00000167232), ZNF526 (ENSG00000167625), ZNF764 (ENSG00000169951), ZNF747 (ENSG00000169955), ZNF282 (ENSG00000170265), ZNF160 (ENSG00000170949), ZNF497 (ENSG00000174586), ZBTB34 (ENSG00000177125), ZNF771 (ENSG00000179965), ZNF48 (ENSG00000180035), ZNF594 (ENSG00000180626), ZBTB37 (ENSG00000185278), ZFP92 (ENSG00000189420), ZNF107 (ENSG00000196247), ZNF729 (ENSG00000196350), ZNF569 (ENSG00000196437), ZNF420 (ENSG00000197050), ZNF785 (ENSG00000197162), ZNF665 (ENSG00000197497), ZNF181 (ENSG00000197841), ZNF347 (ENSG00000197937), ZNF84 (ENSG00000198040), ZBTB48 (ENSG00000204859), ZNF845 (ENSG00000213799), ZNF99 (ENSG00000213973), ZNF688 (ENSG00000229809)

Protein

Protein identifiers

Zinc finger protein 574 — Q6ZN55 (reviewed: Q6ZN55)

All UniProt accessions (3): Q6ZN55, A0A0C4DFM2, M0R133

UniProt curated annotations — full annotation on UniProt →

Function. Part of a ribosome quality control that mediates surveillance of ribosome assembly and promotes degradation of ribosomes with assembly defects.

Subunit / interactions. Associates with defective pre-ribosomes.

Subcellular location. Cytoplasm. Nucleus.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZN55-1	1	yes
Q6ZN55-2	2

RefSeq proteins (2): NP_001317448, NP_073589* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050636	C2H2-ZF_domain-containing	Family

Pfam: PF00096, PF12874, PF13912

UniProt features (40 total): zinc finger region 20, modified residue 7, region of interest 3, compositionally biased region 3, sequence variant 3, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZN55-F1	63.54	0.08

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 (7): 113, 164, 298, 717, 724, 728, 832

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RIBOSOME_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, MARTINEZ_RB1_TARGETS_UP, MARTINEZ_RB1_TARGETS_DN, GOBP_ORGANELLE_ASSEMBLY, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEOLYSIS, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_RIBOSOME_BINDING

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), developmental process (GO:0032502)

GO Molecular Function (4): DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
biological_process	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

892 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF574	TMEM145	Q8NBT3	582
ZNF574	CNFN	Q9BYD5	549
ZNF574	CEACAM7	Q14002	526
ZNF574	PAFAH1B3	Q15102	525
ZNF574	MANBAL	Q9NQG1	490
ZNF574	PLEKHJ1	Q9NW61	477
ZNF574	TRMT1L	Q7Z2T5	451
ZNF574	PRR19	A6NJB7	447
ZNF574	TRMT10A	Q8TBZ6	433
ZNF574	PSG11	Q9UQ72	411
ZNF574	ZNF512	Q96ME7	407
ZNF574	PSG6	Q00889	405
ZNF574	NAA38	Q9BRA0	396
ZNF574	PSG4	Q00888	392
ZNF574	PSG1	P11462	391
ZNF574	TOMM40L	Q969M1	391

IntAct

95 interactions, top by confidence:

A	B	Type	Score
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
THAP12	ZNF574	psi-mi:“MI:0915”(physical association)	0.620
ZNF574	THAP12	psi-mi:“MI:0914”(association)	0.620
N	NOP56	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ZNF689	ZNF593	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZC3HAV1	KHNYN	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
NIFK	RSL1D1	psi-mi:“MI:0914”(association)	0.530
RPSA	RPS17	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZNF574	E2	psi-mi:“MI:0915”(physical association)	0.370
ZNF574	E7	psi-mi:“MI:0915”(physical association)	0.370
ZNF526	VAMP4	psi-mi:“MI:0914”(association)	0.350
Set	ZKSCAN1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
rl3_rl3l_human	NKRF	psi-mi:“MI:0914”(association)	0.350
rl36a_rl36l_human	IPO5	psi-mi:“MI:0914”(association)	0.350
IGHM	ESYT2	psi-mi:“MI:0914”(association)	0.350
RPS19	ZNF320	psi-mi:“MI:0914”(association)	0.350
PURG	ZNF320	psi-mi:“MI:0914”(association)	0.350
ZNF467	ZNF320	psi-mi:“MI:0914”(association)	0.350

BioGRID (301): ZNF574 (Affinity Capture-MS), ZNF574 (Affinity Capture-MS), ZNF574 (Affinity Capture-MS), ZNF574 (Affinity Capture-MS), ZNF574 (Affinity Capture-MS), ZNF574 (Affinity Capture-MS), ZNF574 (Reconstituted Complex), ZNF574 (Affinity Capture-MS), ZNF574 (Affinity Capture-MS), ZNF574 (Affinity Capture-MS), ZNF574 (Affinity Capture-MS), SHCBP1 (Affinity Capture-MS), PRKRIR (Affinity Capture-MS), TRIM41 (Affinity Capture-MS), ANKRD28 (Affinity Capture-MS)

ESM2 similar proteins: A2A5K6, A6QR00, D4A8X0, E9Q6W4, G3V893, O15015, O15156, O95863, P0CJ78, P10074, Q02085, Q13105, Q29RK0, Q3U3I9, Q4R8S8, Q504L7, Q5EBL2, Q5F293, Q5R4P8, Q5RJR4, Q60821, Q66K89, Q6DD87, Q6GL52, Q6NV66, Q6PGE4, Q6YND2, Q6ZN55, Q80VM4, Q8BI66, Q8BI69, Q8BIF9, Q8BY46, Q8CCE9, Q8CJ78, Q8JZL0, Q8N1W2, Q8NCA9, Q8TF50, Q8WUU4

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, E9PW05, E9PZZ1, G5EBU4, O15391, O60315, O62836, O75362, O77459, O95863, P08048, P0CS62, P0CS63, P10925, P15822, P17010, P17012, P20662, P22227, P25490, P28166, P31509, P31629, P36197, P52739, P52746, P56270, P56670, P56671, P60319, P80944, Q00899, Q00900

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 modulates host translation machinery	10	53.2×	4e-14
Eukaryotic Translation Initiation	9	47.9×	2e-12
Cap-dependent Translation Initiation	9	47.9×	2e-12
Eukaryotic Translation Elongation	9	43.2×	4e-12
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	9	42.2×	5e-12
Influenza Viral RNA Transcription and Replication	10	37.1×	1e-12
Nonsense-Mediated Decay (NMD)	9	36.2×	2e-11
SARS-CoV-2 modulates host translation machinery	9	34.8×	3e-11

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	14	28.8×	2e-14
ribosomal small subunit biogenesis	10	25.3×	8e-10
regulation of alternative mRNA splicing, via spliceosome	8	21.7×	3e-07
rRNA processing	11	17.3×	4e-09
translation	13	14.8×	8e-10
RNA splicing	7	6.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	137
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

468 predictions. Top by Δscore:

Variant	Effect	Δscore
19:42078585:A:AG	acceptor_gain	1.0000
19:42078586:G:GA	acceptor_gain	1.0000
19:42078586:GC:G	acceptor_gain	1.0000
19:42078586:GCCC:G	acceptor_gain	1.0000
19:42078586:GCCCA:G	acceptor_gain	1.0000
19:42078572:T:A	acceptor_gain	0.9900
19:42078586:GCC:G	acceptor_gain	0.9900
19:42070967:C:T	donor_gain	0.9700
19:42078570:ACT:A	acceptor_gain	0.9600
19:42078571:C:G	acceptor_gain	0.9600
19:42070905:G:GT	donor_gain	0.9500
19:42070803:A:G	donor_gain	0.9400
19:42070939:C:T	donor_gain	0.9300
19:42076129:G:GT	donor_gain	0.9300
19:42078570:A:AG	acceptor_gain	0.9300
19:42070789:A:T	donor_gain	0.9200
19:42076130:A:T	donor_gain	0.9200
19:42070869:G:GT	donor_gain	0.9100
19:42070870:G:T	donor_gain	0.9100
19:42078581:TTCCA:T	acceptor_gain	0.9000
19:42078582:TCCAG:T	acceptor_gain	0.9000
19:42078583:CCAGC:C	acceptor_gain	0.9000
19:42078584:CAGC:C	acceptor_gain	0.9000
19:42078585:A:C	acceptor_gain	0.9000
19:42078586:G:T	acceptor_gain	0.9000
19:42076282:AGCAG:A	donor_loss	0.8800
19:42076284:CAGGT:C	donor_loss	0.8800
19:42076285:AGG:A	donor_loss	0.8800
19:42076286:GG:G	donor_loss	0.8800
19:42076287:GTGAG:G	donor_loss	0.8800

AlphaMissense

5740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:42080179:T:C	C525R	1.000
19:42080284:T:C	F560L	1.000
19:42080285:T:C	F560S	1.000
19:42080286:C:A	F560L	1.000
19:42080286:C:G	F560L	1.000
19:42080908:T:C	C768R	1.000
19:42080929:T:C	F775L	1.000
19:42080931:C:A	F775L	1.000
19:42080931:C:G	F775L	1.000
19:42081013:T:C	F803L	1.000
19:42081014:T:C	F803S	1.000
19:42081015:T:A	F803L	1.000
19:42081015:T:G	F803L	1.000
19:42081076:T:C	C824R	1.000
19:42078988:T:C	C128R	0.999
19:42079009:T:C	F135L	0.999
19:42079010:T:C	F135S	0.999
19:42079011:T:A	F135L	0.999
19:42079011:T:G	F135L	0.999
19:42079274:T:C	F223S	0.999
19:42079618:T:C	C338R	0.999
19:42079786:T:C	C394R	0.999
19:42079804:T:C	F400L	0.999
19:42079806:T:A	F400L	0.999
19:42079806:T:G	F400L	0.999
19:42080008:T:C	C468R	0.999
19:42080095:T:C	C497R	0.999
19:42080181:C:G	C525W	0.999
19:42080188:T:C	C528R	0.999
19:42080190:C:G	C528W	0.999

dbSNP variants (sampled 300 via entrez): RS1000238800 (19:42068839 G>A), RS1000480941 (19:42081351 A>G), RS1000571702 (19:42069746 G>A,T), RS1000800980 (19:42075327 G>A), RS1000853440 (19:42075577 G>T), RS1000904965 (19:42075167 G>A,C), RS1001063205 (19:42069325 G>A,T), RS1001220306 (19:42066526 G>A), RS1001315755 (19:42074448 C>T), RS1001410872 (19:42069148 G>A,T), RS1001475908 (19:42077949 G>A), RS1001504705 (19:42069498 G>A), RS1001529736 (19:42078276 G>A,T), RS1001740574 (19:42071791 G>A), RS1001807824 (19:42076464 C>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
GCST010143_27	Meat-related diet	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
PCI 5002	increases expression, affects cotreatment	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Potassium Chloride	decreases response to substance, increases expression	1
Smoke	decreases expression	1
Dronabinol	increases expression, decreases response to substance	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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