ZNF558

Summary

ZNF558 (zinc finger protein 558, HGNC:26422) is a protein-coding gene on chromosome 19p13.2, encoding Zinc finger protein 558 (Q96NG5). May be involved in transcriptional regulation.

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

Source: NCBI Gene 148156 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_144693

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26422
Approved symbol	ZNF558
Name	zinc finger protein 558
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30932
Ensembl gene	ENSG00000167785
Ensembl biotype	protein_coding
Entrez	148156

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000301475, ENST00000593891, ENST00000595786, ENST00000596172, ENST00000597304, ENST00000599938, ENST00000601372, ENST00000869419, ENST00000869420, ENST00000869421, ENST00000869422, ENST00000869423, ENST00000971724, ENST00000971725, ENST00000971726, ENST00000971727, ENST00000971728, ENST00000971729, ENST00000971730, ENST00000971731, ENST00000971732, ENST00000971733, ENST00000971734, ENST00000971735

RefSeq mRNA: 1 — MANE Select: NM_144693 NM_144693

CCDS: CCDS12208

Canonical transcript exons

ENST00000601372 — 10 exons

Exon	Start	End
ENSE00001153986	8822003	8822091
ENSE00003012103	8806170	8812063
ENSE00003039224	8831318	8831401
ENSE00003045567	8832209	8832304
ENSE00003049458	8825002	8825108
ENSE00003114735	8824082	8824417
ENSE00003490038	8821180	8821306
ENSE00003543455	8812561	8812643
ENSE00003543535	8822629	8822724
ENSE00003615830	8813127	8813222

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 89.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5479 / max 49.4953, expressed in 1420 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178975	1.8317	1015
178974	1.7161	988

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	89.62	gold quality
cortical plate	UBERON:0005343	89.19	gold quality
secondary oocyte	CL:0000655	89.11	gold quality
left ovary	UBERON:0002119	88.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.88	gold quality
lower esophagus	UBERON:0013473	88.87	gold quality
ganglionic eminence	UBERON:0004023	88.79	gold quality
right uterine tube	UBERON:0001302	88.72	gold quality
tibialis anterior	UBERON:0001385	88.70	silver quality
left uterine tube	UBERON:0001303	88.26	gold quality
right ovary	UBERON:0002118	88.20	gold quality
smooth muscle tissue	UBERON:0001135	88.06	gold quality
epithelial cell of pancreas	CL:0000083	87.67	silver quality
oocyte	CL:0000023	87.52	gold quality
ventricular zone	UBERON:0003053	87.52	gold quality
ovary	UBERON:0000992	87.36	gold quality
oviduct epithelium	UBERON:0004804	87.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.23	gold quality
lower esophagus mucosa	UBERON:0035834	86.75	gold quality
fallopian tube	UBERON:0003889	86.64	gold quality
right lobe of thyroid gland	UBERON:0001119	86.63	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.59	gold quality
endocervix	UBERON:0000458	86.55	gold quality
body of pancreas	UBERON:0001150	86.30	gold quality
left lobe of thyroid gland	UBERON:0001120	86.11	gold quality
thyroid gland	UBERON:0002046	86.08	gold quality
tibia	UBERON:0000979	86.07	gold quality
tibial nerve	UBERON:0001323	85.96	gold quality
descending thoracic aorta	UBERON:0002345	85.87	gold quality
right adrenal gland	UBERON:0001233	85.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.82

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2335.1	ZNF558	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:28273063

miRNA regulators (miRDB)

69 targeting ZNF558, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-545-5P	99.66	70.18	2308

Literature-anchored findings (GeneRIF, showing 1)

• A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development. (PMID:34624206)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp558	ENSMUSG00000074500
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF582 (ENSG00000018869), ZNF264 (ENSG00000083844), ZNF343 (ENSG00000088876), ZNF684 (ENSG00000117010), ZNF133 (ENSG00000125846), ZNF557 (ENSG00000130544), ZNF337 (ENSG00000130684), ZNF20 (ENSG00000132010), ZFP37 (ENSG00000136866), ZNF614 (ENSG00000142556), KRBOX4 (ENSG00000147121), ZNF599 (ENSG00000153896), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF35 (ENSG00000169981), ZNF778 (ENSG00000170100), ZNF439 (ENSG00000171291), ZNF440 (ENSG00000171295), ZNF556 (ENSG00000172000), ZNF554 (ENSG00000172006), ZNF596 (ENSG00000172748), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF404 (ENSG00000176222), ZNF491 (ENSG00000177599), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF875 (ENSG00000181666), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300), ZNF70 (ENSG00000187792)

Protein

Protein identifiers

Zinc finger protein 558 — Q96NG5 (reviewed: Q96NG5)

All UniProt accessions (1): Q96NG5

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96NG5-1	1	yes
Q96NG5-2	2

RefSeq proteins (1): NP_653294* (*=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, PF13465, PF13912

UniProt features (12 total): zinc finger region 9, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NG5-F1	73.94	0.33

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 46 (showing top): chr19p13, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CHAF1B_TARGET_GENES, DIDO1_TARGET_GENES, ELF2_TARGET_GENES, KAT5_TARGET_GENES, LHX9_TARGET_GENES, NFKBIA_TARGET_GENES, RBM34_TARGET_GENES, ZBTB12_TARGET_GENES, ZNF146_TARGET_GENES, MIR300, MIR381_3P, MIR33A_3P

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 transcription regulatory region sequence-specific DNA binding (GO:0000977), 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
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
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	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

616 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF558	TRIM61	Q5EBN2	644
ZNF558	OR2Z1	Q8NG97	635
ZNF558	SPATA18	Q8TC71	478
ZNF558	MBD3L1	Q8WWY6	469
ZNF558	LCE2D	Q5TA82	413
ZNF558	TAF9B	Q9HBM6	396
ZNF558	MAGEA11	P43364	394
ZNF558	PRAMEF14	Q5SWL7	366
ZNF558	ZNF608	Q9ULD9	365
ZNF558	ZZZ3	Q8IYH5	359
ZNF558	FCGR2A	P12318	353
ZNF558	ACTL9	Q8TC94	352
ZNF558	FSTL4	Q6MZW2	346
ZNF558	ZBTB21	Q9ULJ3	342
ZNF558	C9JR48	C9JR48	327

IntAct

36 interactions, top by confidence:

A	B	Type	Score
GSDMD	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
LZIC	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
MFAP1	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
CLK2	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
HEXIM2	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
ZNF558	MAD2L2	psi-mi:“MI:0915”(physical association)	0.560
EIF1AD	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
UBTFL1	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
CSNK2A1	ZNF558	psi-mi:“MI:0915”(physical association)	0.560
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
ZNF558	RCBTB2	psi-mi:“MI:0914”(association)	0.350
ZNF558	SERPINA1	psi-mi:“MI:0914”(association)	0.350
CLK2	ZNF558	psi-mi:“MI:0915”(physical association)	0.000
EFEMP2	ZNF558	psi-mi:“MI:0915”(physical association)	0.000
LZIC	ZNF558	psi-mi:“MI:0915”(physical association)	0.000
MFAP1	ZNF558	psi-mi:“MI:0915”(physical association)	0.000
HEXIM2	ZNF558	psi-mi:“MI:0915”(physical association)	0.000
UBTFL1	ZNF558	psi-mi:“MI:0915”(physical association)	0.000
CSNK2A1	ZNF558	psi-mi:“MI:0915”(physical association)	0.000
MAD2L2	ZNF558	psi-mi:“MI:0915”(physical association)	0.000
EIF1AD	ZNF558	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): ZNF558 (Affinity Capture-RNA), ZNF558 (Affinity Capture-RNA), ALB (Affinity Capture-MS), APOA1 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), RCBTB2 (Affinity Capture-MS), APOA1 (Affinity Capture-MS), SERPINA1 (Affinity Capture-MS), RCBTB2 (Affinity Capture-MS), FTL (Affinity Capture-MS), ALB (Affinity Capture-MS), ZNF558 (Two-hybrid), ZNF558 (Two-hybrid), ZNF558 (Two-hybrid), ZNF558 (Two-hybrid)

ESM2 similar proteins: A0JPL0, A1L1L7, A3KN32, A3KN36, D3ZVT0, O43296, P08042, P16373, P17023, P17031, P52738, P85977, Q02975, Q12901, Q14592, Q29RZ4, Q3KNS6, Q4R6J4, Q4V8A8, Q571J5, Q5CZA5, Q5JNZ3, Q5R7I8, Q5RB33, Q5RBY9, Q5T5D7, Q61751, Q61967, Q62396, Q6GQR8, Q6ZNG0, Q6ZS27, Q7Z398, Q8BI99, Q8BIQ3, Q8IVC4, Q8IZ26, Q8N988, Q8N9Z0, Q8NDP4

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1788 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8812555:TCTTA:T	donor_loss	1.0000
19:8812556:CTTAC:C	donor_loss	1.0000
19:8812557:TTACC:T	donor_loss	1.0000
19:8812558:TACCG:T	donor_loss	1.0000
19:8812559:A:C	donor_loss	1.0000
19:8812560:C:CT	donor_loss	1.0000
19:8812640:AAATC:A	acceptor_loss	1.0000
19:8812642:ATCTG:A	acceptor_loss	1.0000
19:8812643:TC:T	acceptor_loss	1.0000
19:8812644:C:A	acceptor_loss	1.0000
19:8812644:C:CC	acceptor_gain	1.0000
19:8812645:T:G	acceptor_loss	1.0000
19:8813121:GCTCA:G	donor_loss	1.0000
19:8813122:CTCA:C	donor_loss	1.0000
19:8813124:CAC:C	donor_loss	1.0000
19:8813125:A:AT	donor_loss	1.0000
19:8813219:CACC:C	acceptor_gain	1.0000
19:8813221:CC:C	acceptor_gain	1.0000
19:8813222:CCTA:C	acceptor_gain	1.0000
19:8813223:CT:C	acceptor_loss	1.0000
19:8813224:T:C	acceptor_loss	1.0000
19:8821174:GCTTA:G	donor_loss	1.0000
19:8821175:CTTAC:C	donor_loss	1.0000
19:8821176:TTACC:T	donor_loss	1.0000
19:8821177:TACCT:T	donor_loss	1.0000
19:8821178:A:AC	donor_gain	1.0000
19:8821178:ACCTA:A	donor_loss	1.0000
19:8821179:C:CA	donor_gain	1.0000
19:8821179:CCT:C	donor_gain	1.0000
19:8821179:CCTA:C	donor_gain	1.0000

AlphaMissense

2679 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8811503:G:C	F329L	0.996
19:8811503:G:T	F329L	0.996
19:8811505:A:G	F329L	0.996
19:8811587:G:C	F301L	0.996
19:8811587:G:T	F301L	0.996
19:8811589:A:G	F301L	0.996
19:8811839:A:C	F217L	0.996
19:8811839:A:T	F217L	0.996
19:8811841:A:G	F217L	0.996
19:8811335:G:C	F385L	0.995
19:8811335:G:T	F385L	0.995
19:8811337:A:G	F385L	0.995
19:8811671:G:C	F273L	0.995
19:8811671:G:T	F273L	0.995
19:8811673:A:G	F273L	0.995
19:8811755:G:C	F245L	0.995
19:8811755:G:T	F245L	0.995
19:8811757:A:G	F245L	0.995
19:8811923:G:C	F189L	0.995
19:8811923:G:T	F189L	0.995
19:8811925:A:G	F189L	0.995
19:8811419:A:C	F357L	0.994
19:8811419:A:T	F357L	0.994
19:8811421:A:G	F357L	0.994
19:8811560:G:C	H310Q	0.992
19:8811560:G:T	H310Q	0.992
19:8811812:A:C	H226Q	0.992
19:8811812:A:T	H226Q	0.992
19:8811570:A:G	L307P	0.991
19:8811906:A:G	L195P	0.991

dbSNP variants (sampled 300 via entrez): RS1000158420 (19:8835918 C>A,T), RS1000201811 (19:8838878 A>G), RS1000262306 (19:8821049 G>A,C,T), RS1000263113 (19:8823228 C>T), RS1000326254 (19:8828063 T>A,C), RS1000459045 (19:8833545 GTC>G), RS1000577804 (19:8836523 G>A), RS1000726641 (19:8830994 T>C), RS1000796399 (19:8825696 A>T), RS1000831242 (19:8833342 A>G,T), RS1000894868 (19:8815576 T>C,G), RS1000906547 (19:8836711 C>T), RS1000977232 (19:8819734 T>C), RS1001070718 (19:8806079 T>C), RS1001279527 (19:8824561 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
cupric oxide	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression, affects cotreatment	1
Particulate Matter	increases abundance, 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_HD28	HEK293 eGFP-ZNF558	Transformed cell line	Female

Clinical trials (associated diseases)

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