ZNF578

Summary

ZNF578 (zinc finger protein 578, HGNC:26449) is a protein-coding gene on chromosome 19q13.41, encoding Zinc finger protein 578 (Q96N58). May be involved in transcriptional regulation.

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

Source: NCBI Gene 147660 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 120 total
• MANE Select transcript: NM_001099694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26449
Approved symbol	ZNF578
Name	zinc finger protein 578
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31384
Ensembl gene	ENSG00000258405
Ensembl biotype	protein_coding
Entrez	147660

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000421239, ENST00000601120

RefSeq mRNA: 2 — MANE Select: NM_001099694 NM_001099694, NM_001366182

CCDS: CCDS54310

Canonical transcript exons

ENST00000421239 — 6 exons

Exon	Start	End
ENSE00001695744	52510572	52516882
ENSE00002431956	52504655	52504781
ENSE00002633778	52453553	52453607
ENSE00002648745	52501827	52501908
ENSE00002676555	52491324	52491425
ENSE00003889647	52456868	52456958

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 84.48.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0547 / max 58.5584, expressed in 794 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177307	1.3603	698
177308	0.6944	134

Top tissues by expression

133 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	84.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.69	gold quality
cortical plate	UBERON:0005343	78.34	gold quality
ganglionic eminence	UBERON:0004023	73.34	gold quality
ventricular zone	UBERON:0003053	71.41	gold quality
testis	UBERON:0000473	70.69	gold quality
stromal cell of endometrium	CL:0002255	69.68	gold quality
right testis	UBERON:0004534	69.21	gold quality
endometrium	UBERON:0001295	69.00	gold quality
left testis	UBERON:0004533	68.45	gold quality
calcaneal tendon	UBERON:0003701	68.18	gold quality
granulocyte	CL:0000094	66.89	gold quality
cerebellar cortex	UBERON:0002129	66.79	gold quality
cerebellum	UBERON:0002037	66.77	gold quality
cerebellar hemisphere	UBERON:0002245	66.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.83	gold quality
apex of heart	UBERON:0002098	65.65	gold quality
nucleus accumbens	UBERON:0001882	65.63	gold quality
corpus callosum	UBERON:0002336	65.60	gold quality
cortex of kidney	UBERON:0001225	64.85	gold quality
placenta	UBERON:0001987	64.77	gold quality
putamen	UBERON:0001874	64.75	gold quality
caudate nucleus	UBERON:0001873	64.61	gold quality
heart left ventricle	UBERON:0002084	64.60	gold quality
kidney	UBERON:0002113	64.27	gold quality
heart	UBERON:0000948	63.38	gold quality
adult mammalian kidney	UBERON:0000082	63.22	gold quality
islet of Langerhans	UBERON:0000006	62.97	gold quality
myometrium	UBERON:0001296	62.96	gold quality
smooth muscle tissue	UBERON:0001135	62.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.84
E-CURD-89	no	140.32

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (11): ZNF761 (ENSG00000160336), ZNF701 (ENSG00000167562), ZNF816 (ENSG00000180257), ZNF766 (ENSG00000196214), ZNF765 (ENSG00000196417), ZNF860 (ENSG00000197385), ZNF813 (ENSG00000198346), ZNF525 (ENSG00000203326), ZNF468 (ENSG00000204604), ZNF888 (ENSG00000213793), (ENSG00000269825)

Protein

Protein identifiers

Zinc finger protein 578 — Q96N58 (reviewed: Q96N58)

All UniProt accessions (2): Q96N58, M0QZV4

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.

RefSeq proteins (2): NP_001093164, NP_001353111 (=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, PF13912

UniProt features (15 total): zinc finger region 12, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N58-F1	65.31	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, TRIP13_TARGET_GENES, MIR616_5P, MIR371B_5P, MIR373_5P, MIR6809_3P, MIR6833_3P, MIR6873_3P, MIR4768_5P, MIR450A_1_3P, MIR3925_3P, MIR3064_3P, MIR19A_5P

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 cis-regulatory region sequence-specific DNA binding (GO:0000978), 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)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
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
cis-regulatory region sequence-specific DNA binding	1
chromatin	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

347 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF578	DAP3	P51398	493
ZNF578	PKIB	Q9C010	491
ZNF578	NUP210L	Q5VU65	447
ZNF578	Q6GMV1	Q6GMV1	432
ZNF578	C12orf42	Q96LP6	413
ZNF578	GOLPH3L	Q9H4A5	398
ZNF578	SLC4A8	Q2Y0W8	383
ZNF578	TBL1Y	Q9BQ87	373
ZNF578	RNASEH1	O60930	372
ZNF578	KLHDC4	Q8TBB5	359
ZNF578	ABCC2	Q92887	353
ZNF578	CPN2	P22792	348
ZNF578	TCEAL2	Q9H3H9	348
ZNF578	TBL1X	O60907	348
ZNF578	LRRC41	Q15345	336

IntAct

38 interactions, top by confidence:

A	B	Type	Score
KRTAP12-3	ZNF578	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	ZNF578	psi-mi:“MI:0915”(physical association)	0.560
ZNF578	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
ZNF526	ZNF578	psi-mi:“MI:0915”(physical association)	0.560
CCNDBP1	ZNF578	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	ZNF578	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	ZNF578	psi-mi:“MI:0915”(physical association)	0.560
ZNF578	CIB3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	ZNF578	psi-mi:“MI:0915”(physical association)	0.560
ZNF578	KRTAP17-1	psi-mi:“MI:0915”(physical association)	0.560
ZNF578	MDFI	psi-mi:“MI:0915”(physical association)	0.560
CEP70	ZNF578	psi-mi:“MI:0915”(physical association)	0.560
ZNF578	IPO8	psi-mi:“MI:0914”(association)	0.350
ZNF578	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	GOLGA6L9	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	MDFI	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	ZNF526	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.000
GOLGA6L9	ZNF578	psi-mi:“MI:0915”(physical association)	0.000
ZNF526	ZNF578	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	CEP70	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	KRTAP17-1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): ZNF578 (Two-hybrid), ZNF578 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), ZNF578 (Two-hybrid), ZNF578 (Two-hybrid), ZNF578 (Two-hybrid), ZNF578 (Two-hybrid), ZNF578 (Two-hybrid), ZNF578 (Two-hybrid), ZNF578 (Two-hybrid), ZNF578 (Two-hybrid), ZNF578 (Two-hybrid)

ESM2 similar proteins: A0A087WUV0, A0JNB1, A2VDP4, B2RUI1, P0CG31, P10072, P17025, P17036, P17097, P18733, P51814, Q08ER8, Q09FC8, Q0VGE8, Q14590, Q15937, Q16600, Q2M3X9, Q4V8A8, Q5CZA5, Q5R8G9, Q5RBX0, Q5VIY5, Q68DI1, Q6J6I6, Q6NX49, Q6P1L6, Q6PG37, Q6ZMS4, Q6ZMW2, Q80YP6, Q86UD4, Q86Y25, Q8IZ26, Q8N184, Q8NB42, Q8NEK5, Q8TAF7, Q8TF47, Q8WXB4

Diamond homologs: A0A1W2PQL4, A2RRD8, A2VDQ7, A6NHJ4, A6NK75, A6NN14, A6NNF4, A6NP11, B4DX44, B4DXR9, E9PW05, O14628, O43345, O75290, O75346, O75373, O75820, P0CB33, P0CJ79, P0DKX0, P10755, P17032, P17035, P52738, Q02386, Q03923, Q03936, Q05481, Q08AN1, Q09FC8, Q0VGE8, Q14586, Q14593, Q147U1, Q15928, Q3MIS6, Q3SXZ3, Q494X3, Q4R6C2, Q5HY98

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1218 predictions. Top by Δscore:

Variant	Effect	Δscore
19:52456947:A:T	donor_gain	1.0000
19:52481415:GGCCC:G	donor_gain	1.0000
19:52501820:C:G	acceptor_gain	1.0000
19:52501822:T:G	acceptor_gain	1.0000
19:52501822:TACAG:T	acceptor_loss	1.0000
19:52501825:A:AG	acceptor_gain	1.0000
19:52501825:AG:A	acceptor_gain	1.0000
19:52501825:AGG:A	acceptor_loss	1.0000
19:52501826:G:GC	acceptor_loss	1.0000
19:52501826:G:GG	acceptor_gain	1.0000
19:52501826:GG:G	acceptor_gain	1.0000
19:52501826:GGATT:G	acceptor_gain	1.0000
19:52501904:CTCAG:C	donor_loss	1.0000
19:52501906:CAGG:C	donor_loss	1.0000
19:52501907:AG:A	donor_loss	1.0000
19:52501908:GGT:G	donor_loss	1.0000
19:52501910:T:G	donor_loss	1.0000
19:52504742:G:T	donor_gain	1.0000
19:52504774:GGCT:G	donor_gain	1.0000
19:52504775:GCTG:G	donor_gain	1.0000
19:52510571:GAT:G	acceptor_gain	1.0000
19:52456866:A:AG	acceptor_gain	0.9900
19:52456866:AG:A	acceptor_gain	0.9900
19:52456867:G:GG	acceptor_gain	0.9900
19:52456867:GG:G	acceptor_gain	0.9900
19:52456867:GGATT:G	acceptor_gain	0.9900
19:52456946:G:GT	donor_gain	0.9900
19:52456954:CTTAG:C	donor_loss	0.9900
19:52456955:TTAGG:T	donor_loss	0.9900
19:52456956:TAGG:T	donor_loss	0.9900

AlphaMissense

3965 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:52511603:T:C	F408L	0.996
19:52511605:T:A	F408L	0.996
19:52511605:T:G	F408L	0.996
19:52511939:T:C	F520L	0.996
19:52511941:T:A	F520L	0.996
19:52511941:T:G	F520L	0.996
19:52512023:T:C	F548L	0.995
19:52512025:C:A	F548L	0.995
19:52512025:C:G	F548L	0.995
19:52511687:T:C	F436L	0.994
19:52511689:T:A	F436L	0.994
19:52511689:T:G	F436L	0.994
19:52511855:T:C	F492L	0.994
19:52511857:C:A	F492L	0.994
19:52511857:C:G	F492L	0.994
19:52511351:T:C	F324L	0.993
19:52511353:C:A	F324L	0.993
19:52511353:C:G	F324L	0.993
19:52511435:T:C	F352L	0.993
19:52511437:C:A	F352L	0.993
19:52511437:C:G	F352L	0.993
19:52511267:T:C	F296L	0.988
19:52511269:C:A	F296L	0.988
19:52511269:C:G	F296L	0.988
19:52511622:T:C	L414P	0.987
19:52511771:T:C	F464L	0.987
19:52511773:C:A	F464L	0.987
19:52511773:C:G	F464L	0.987
19:52511964:G:C	R528P	0.987
19:52511630:C:G	H417D	0.983

dbSNP variants (sampled 300 via entrez): RS1000002374 (19:52480238 T>G), RS1000005141 (19:52508748 T>C), RS1000063774 (19:52466795 A>G), RS1000077397 (19:52473217 C>A,T), RS1000094713 (19:52472065 T>A,G), RS1000128919 (19:52507645 T>C), RS1000142400 (19:52456293 G>A), RS1000158853 (19:52496177 C>A,G), RS1000200471 (19:52492323 G>A), RS1000277978 (19:52475241 A>G), RS1000306498 (19:52495855 C>G), RS1000328185 (19:52463183 C>G,T), RS1000372734 (19:52467137 A>G), RS1000480628 (19:52457698 A>C), RS1000554801 (19:52516925 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

2 associations (top):

Study	Trait	p-value
GCST002981_4	Longitudinal alcohol consumption	3.000000e-07
GCST008158_83	Body mass index	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
aflatoxin B2	increases methylation	1
hydroquinone	increases expression	1
Formaldehyde	increases expression	1
Oxygen	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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