ZNF557

Summary

ZNF557 (zinc finger protein 557, HGNC:28632) is a protein-coding gene on chromosome 19p13.2, encoding Zinc finger protein 557 (Q8N988). 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 79230 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_024341

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28632
Approved symbol	ZNF557
Name	zinc finger protein 557
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC4054
Ensembl gene	ENSG00000130544
Ensembl biotype	protein_coding
Entrez	79230

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000252840, ENST00000414706, ENST00000882902, ENST00000882903, ENST00000882904, ENST00000882905, ENST00000936561, ENST00000944189, ENST00000944190, ENST00000944191

RefSeq mRNA: 3 — MANE Select: NM_024341 NM_001044387, NM_001044388, NM_024341

CCDS: CCDS42485, CCDS45945

Canonical transcript exons

ENST00000252840 — 8 exons

Exon	Start	End
ENSE00001053357	7070562	7070653
ENSE00001053360	7069703	7069773
ENSE00001053363	7074996	7075105
ENSE00001157657	7081360	7081455
ENSE00001286143	7082878	7087968
ENSE00001300243	7075655	7075743
ENSE00001724023	7076381	7076507
ENSE00001774114	7081970	7082052

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 82.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5473 / max 75.0329, expressed in 1792 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173527	9.4835	1775
173526	2.0638	1221

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.93	gold quality
calcaneal tendon	UBERON:0003701	74.62	gold quality
cortical plate	UBERON:0005343	73.97	gold quality
granulocyte	CL:0000094	73.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.50	gold quality
stromal cell of endometrium	CL:0002255	73.05	gold quality
ganglionic eminence	UBERON:0004023	71.84	gold quality
adrenal tissue	UBERON:0018303	71.02	gold quality
ventricular zone	UBERON:0003053	70.29	gold quality
leukocyte	CL:0000738	70.26	gold quality
monocyte	CL:0000576	70.03	gold quality
mononuclear cell	CL:0000842	69.84	gold quality
tendon	UBERON:0000043	69.75	gold quality
islet of Langerhans	UBERON:0000006	68.91	gold quality
colonic epithelium	UBERON:0000397	66.86	silver quality
hindlimb stylopod muscle	UBERON:0004252	65.48	gold quality
smooth muscle tissue	UBERON:0001135	64.82	gold quality
bone marrow cell	CL:0002092	64.58	silver quality
right adrenal gland	UBERON:0001233	64.52	gold quality
left adrenal gland	UBERON:0001234	64.40	gold quality
adrenal gland	UBERON:0002369	64.33	gold quality
lymph node	UBERON:0000029	64.32	gold quality
right adrenal gland cortex	UBERON:0035827	64.25	gold quality
pancreas	UBERON:0001264	64.20	gold quality
mucosa of transverse colon	UBERON:0004991	64.05	gold quality
tonsil	UBERON:0002372	63.98	gold quality
rectum	UBERON:0001052	63.92	gold quality
left adrenal gland cortex	UBERON:0035825	63.84	gold quality
tendon of biceps brachii	UBERON:0008188	63.44	silver quality
vermiform appendix	UBERON:0001154	62.92	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.07
E-MTAB-7303	no	183.87
E-MTAB-6142	no	36.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

141 targeting ZNF557, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-1305	99.91	71.43	3443

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF582 (ENSG00000018869), ZNF264 (ENSG00000083844), ZNF343 (ENSG00000088876), ZNF684 (ENSG00000117010), ZNF133 (ENSG00000125846), ZNF337 (ENSG00000130684), ZNF20 (ENSG00000132010), ZFP37 (ENSG00000136866), ZNF614 (ENSG00000142556), KRBOX4 (ENSG00000147121), ZNF599 (ENSG00000153896), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF558 (ENSG00000167785), 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 557 — Q8N988 (reviewed: Q8N988)

All UniProt accessions (1): Q8N988

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?
Q8N988-1	1	yes
Q8N988-2	2

RefSeq proteins (3): NP_001037852, NP_001037853, NP_077317* (*=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
IPR050758	Znf_C2H2-type	Family

Pfam: PF00096, PF01352, PF13465

UniProt features (13 total): zinc finger region 10, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N988-F1	75.19	0.23

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 72 (showing top): HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, PARENT_MTOR_SIGNALING_UP, CHEN_HOXA5_TARGETS_9HR_UP, chr19p13, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, TBK1.DF_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ATF6_TARGET_GENES, DMRT1_TARGET_GENES, ELF2_TARGET_GENES, NAB2_TARGET_GENES, RFX7_TARGET_GENES, ZNF30_TARGET_GENES

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

GO Molecular Function (7): 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), 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	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF557	RABEPK	Q7Z6M1	536
ZNF557	MBD3L4	A6NDZ8	528
ZNF557	LRRC8E	Q6NSJ5	476
ZNF557	OR4F17	Q8NGA8	471
ZNF557	TTC8	Q8TAM2	468
ZNF557	C2orf42	Q9NWW7	449
ZNF557	ALDH6A1	Q02252	444
ZNF557	MRC2	Q9UBG0	438
ZNF557	FRG2B	Q96QU4	433
ZNF557	ZC2HC1C	Q53FD0	432
ZNF557	MBD3L3	A6NE82	417
ZNF557	CLEC4E	Q9ULY5	405
ZNF557	THAP6	Q8TBB0	402
ZNF557	SS18L2	Q9UHA2	402
ZNF557	MBD3L5	A6NJ08	375

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
SMAD9	ZNF557	psi-mi:“MI:0915”(physical association)	0.370
ZNF557	SUV39H2	psi-mi:“MI:0915”(physical association)	0.370
ZNF557	CEP70	psi-mi:“MI:0915”(physical association)	0.370
ZNF557	IPO8	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): ZNF557 (Two-hybrid), ZNF557 (Two-hybrid), ZNF557 (Two-hybrid), CEP70 (Two-hybrid), ZNF557 (Two-hybrid), MTUS2 (Two-hybrid), CCNDBP1 (Two-hybrid), CCDC125 (Two-hybrid), GOLGA6L9 (Two-hybrid), ZNF557 (Affinity Capture-MS), ZNF557 (Affinity Capture-MS), ZNF557 (Affinity Capture-MS), ZNF557 (Proximity Label-MS), ZNF557 (Proximity Label-MS), ZNF557 (Proximity Label-MS)

ESM2 similar proteins: A2RRD8, A6NHJ4, B4DX44, O75346, P10077, P10755, P15621, P16372, P16373, P51786, P52737, P85977, Q0VGE8, Q14588, Q147U1, Q15928, Q15973, Q2M3X9, Q3KNS6, Q3MIS6, Q494X3, Q5HY98, Q5RBQ3, Q5REK1, Q5VIY5, Q60585, Q61751, Q6GQR8, Q7L2R6, Q7TSH9, Q8IYX0, Q8N782, Q8N823, Q8N988, Q8N9F8, Q8NA42, Q8NCK3, Q8NDP4, Q8NEP9, Q8TC21

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

974 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7069774:G:GG	donor_gain	1.0000
19:7074994:A:AG	acceptor_gain	1.0000
19:7074994:AG:A	acceptor_gain	1.0000
19:7074994:AGGGT:A	acceptor_gain	1.0000
19:7074995:G:GG	acceptor_gain	1.0000
19:7074995:GG:G	acceptor_gain	1.0000
19:7074995:GGGT:G	acceptor_gain	1.0000
19:7074995:GGGTG:G	acceptor_gain	1.0000
19:7075102:GCCG:G	donor_gain	1.0000
19:7075103:CCG:C	donor_gain	1.0000
19:7075106:G:C	donor_loss	1.0000
19:7075106:G:GG	donor_gain	1.0000
19:7075107:T:G	donor_loss	1.0000
19:7076380:GGGC:G	acceptor_gain	1.0000
19:7076503:ACTGG:A	donor_gain	1.0000
19:7076504:CTGG:C	donor_gain	1.0000
19:7076505:TGG:T	donor_gain	1.0000
19:7076506:GG:G	donor_gain	1.0000
19:7076506:GGG:G	donor_gain	1.0000
19:7076507:GG:G	donor_gain	1.0000
19:7076508:G:C	donor_loss	1.0000
19:7076508:G:GG	donor_gain	1.0000
19:7081353:T:G	acceptor_gain	1.0000
19:7081354:GTACA:G	acceptor_loss	1.0000
19:7081355:TACAG:T	acceptor_loss	1.0000
19:7081356:ACAG:A	acceptor_gain	1.0000
19:7081356:ACAGG:A	acceptor_gain	1.0000
19:7081357:CA:C	acceptor_loss	1.0000
19:7081358:A:AG	acceptor_gain	1.0000
19:7081358:AG:A	acceptor_gain	1.0000

AlphaMissense

2853 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7083100:T:C	F210L	0.998
19:7083102:C:A	F210L	0.998
19:7083102:C:G	F210L	0.998
19:7083184:T:C	F238L	0.998
19:7083186:C:A	F238L	0.998
19:7083186:C:G	F238L	0.998
19:7083436:T:C	F322L	0.998
19:7083438:C:A	F322L	0.998
19:7083438:C:G	F322L	0.998
19:7083455:T:C	L328P	0.998
19:7083520:T:C	F350L	0.997
19:7083522:T:A	F350L	0.997
19:7083522:T:G	F350L	0.997
19:7083465:C:A	H331Q	0.996
19:7083465:C:G	H331Q	0.996
19:7083477:T:A	H335Q	0.996
19:7083477:T:G	H335Q	0.996
19:7083539:T:C	L356P	0.996
19:7083268:T:C	F266L	0.995
19:7083270:C:A	F266L	0.995
19:7083270:C:G	F266L	0.995
19:7083688:T:C	F406L	0.995
19:7083690:C:A	F406L	0.995
19:7083690:C:G	F406L	0.995
19:7083119:T:C	L216P	0.994
19:7083185:T:C	F238S	0.994
19:7083352:T:C	F294L	0.994
19:7083354:C:A	F294L	0.994
19:7083354:C:G	F294L	0.994
19:7083371:T:C	L300P	0.994

dbSNP variants (sampled 300 via entrez): RS1000324555 (19:7074094 A>G), RS1000374614 (19:7079703 G>A), RS1000605260 (19:7074387 A>G), RS1000655743 (19:7085780 C>A,G), RS1000773911 (19:7068737 A>G), RS1000803783 (19:7074242 G>A), RS1000963681 (19:7072608 C>T), RS1001019963 (19:7083934 A>G), RS1001250866 (19:7084448 T>A), RS1001376196 (19:7078732 A>G), RS1001409437 (19:7072860 C>G), RS1001848375 (19:7069911 C>T), RS1001934401 (19:7080225 A>C), RS1002006239 (19:7073065 A>G), RS1002190902 (19:7077112 C>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

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Nickel	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
geraniol	increases expression	1
sodium arsenite	increases abundance, increases expression	1
cupric oxide	increases expression	1
resorcinol	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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