ZNF581

Summary

ZNF581 (zinc finger protein 581, HGNC:25017) is a protein-coding gene on chromosome 19q13.42, encoding Zinc finger protein 581 (Q9P0T4). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity 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 nucleus.

Source: NCBI Gene 51545 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_016535

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25017
Approved symbol	ZNF581
Name	zinc finger protein 581
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	HSPC189, FLJ22550
Ensembl gene	ENSG00000171425
Ensembl biotype	protein_coding
Entrez	51545

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000270451, ENST00000585995, ENST00000587252, ENST00000588537, ENST00000899838, ENST00000899839, ENST00000928293, ENST00000928294, ENST00000928295, ENST00000957826

RefSeq mRNA: 1 — MANE Select: NM_016535 NM_016535

CCDS: CCDS12932

Canonical transcript exons

ENST00000270451 — 2 exons

Exon	Start	End
ENSE00001509539	55643649	55643774
ENSE00003850765	55644553	55645623

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 93.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.1997 / max 352.4811, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177661	53.1997	1818
177657	28.1466	1807

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.80	gold quality
upper arm skin	UBERON:0004263	91.75	silver quality
left ventricle myocardium	UBERON:0006566	91.34	gold quality
lower esophagus mucosa	UBERON:0035834	90.73	gold quality
granulocyte	CL:0000094	90.64	gold quality
left ovary	UBERON:0002119	89.98	gold quality
tendon of biceps brachii	UBERON:0008188	89.52	silver quality
leukocyte	CL:0000738	89.27	gold quality
monocyte	CL:0000576	89.16	gold quality
body of pancreas	UBERON:0001150	89.09	gold quality
right ovary	UBERON:0002118	89.09	gold quality
blood	UBERON:0000178	88.93	gold quality
ovary	UBERON:0000992	87.77	gold quality
skin of leg	UBERON:0001511	87.58	gold quality
skin of abdomen	UBERON:0001416	87.48	gold quality
apex of heart	UBERON:0002098	87.43	gold quality
spleen	UBERON:0002106	87.27	gold quality
oocyte	CL:0000023	87.04	gold quality
endocervix	UBERON:0000458	86.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.68	gold quality
body of stomach	UBERON:0001161	86.45	gold quality
right uterine tube	UBERON:0001302	86.37	gold quality
zone of skin	UBERON:0000014	86.34	gold quality
right adrenal gland cortex	UBERON:0035827	86.33	gold quality
esophagus mucosa	UBERON:0002469	86.24	gold quality
stromal cell of endometrium	CL:0002255	86.22	gold quality
ectocervix	UBERON:0012249	86.21	gold quality
right adrenal gland	UBERON:0001233	85.93	gold quality
body of uterus	UBERON:0009853	85.86	gold quality
left adrenal gland cortex	UBERON:0035825	85.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting ZNF581, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-492	94.02	64.46	413

Cross-species orthologs

0 orthologs

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger protein 581 — Q9P0T4 (reviewed: Q9P0T4)

All UniProt accessions (2): Q9P0T4, K7EM32

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_057619* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13894

UniProt features (8 total): zinc finger region 4, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0T4-F1	70.16	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, FOXO4_01, ACEVEDO_LIVER_CANCER_UP, GARY_CD5_TARGETS_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, KRIEG_HYPOXIA_NOT_VIA_KDM3A, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ALKBH3_TARGET_GENES, ARID5B_TARGET_GENES, ARNT2_TARGET_GENES, CEBPZ_TARGET_GENES, DIDO1_TARGET_GENES, DLX4_TARGET_GENES, ELF2_TARGET_GENES

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity (GO:0003700), 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
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	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

312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF581	CCDC97	Q96F63	593
ZNF581	DYRK1B	Q9Y463	367
ZNF581	ALPK2	Q86TB3	302
ZNF581	MAP3K19	Q56UN5	286
ZNF581	DYRK4	Q9NR20	248
ZNF581	DYRK1A	Q13627	246
ZNF581	TRIM25	Q14258	244
ZNF581	OTOA	Q7RTW8	238
ZNF581	DYRK3	O43781	196
ZNF581	CRIM1	Q9NZV1	177
ZNF581	DYRK2	Q92630	153
ZNF581	PRRX1	P54821	133
ZNF581	MAPK7	Q13164	97
ZNF581	CARD11	Q9BXL7	91
ZNF581	GPATCH3	Q96I76	80

IntAct

384 interactions, top by confidence:

A	B	Type	Score
TRIM23	ZNF581	psi-mi:“MI:0915”(physical association)	0.830
ZNF581	MDFI	psi-mi:“MI:0915”(physical association)	0.830
ZNF581	TRIM23	psi-mi:“MI:0915”(physical association)	0.830
MDFI	ZNF581	psi-mi:“MI:0915”(physical association)	0.830
PNMA1	ZNF581	psi-mi:“MI:0915”(physical association)	0.790
ZNF581	PNMA1	psi-mi:“MI:0915”(physical association)	0.790
ZNF581	FSD2	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	ZNF581	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	ZNF581	psi-mi:“MI:0915”(physical association)	0.720
KRT40	ZNF581	psi-mi:“MI:0915”(physical association)	0.720
ZNF581	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
LNX1	ZNF581	psi-mi:“MI:0915”(physical association)	0.720
TRAF4	ZNF581	psi-mi:“MI:0915”(physical association)	0.720
ZNF581	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
ZNF581	KRT40	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	ZNF581	psi-mi:“MI:0915”(physical association)	0.720
ZNF581	LNX1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (145): ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid), ZNF581 (Two-hybrid)

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: Q96C55, Q9D0B1, Q9DB38, Q9P0T4, Q9UK33, Q5NBY9, Q9HBE1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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
Keratinization	11	17.0×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1336 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55635628:GGACA:G	donor_gain	1.0000
19:55635629:GACA:G	donor_gain	1.0000
19:55635619:G:GT	donor_gain	0.9900
19:55635636:G:GG	donor_gain	0.9900
19:55641088:G:GT	donor_gain	0.9900
19:55641122:G:T	donor_gain	0.9900
19:55641180:CGGGG:C	donor_loss	0.9900
19:55641181:GGG:G	donor_gain	0.9900
19:55641181:GGGGT:G	donor_loss	0.9900
19:55641182:GG:G	donor_gain	0.9900
19:55641182:GGG:G	donor_gain	0.9900
19:55641182:GGGTA:G	donor_loss	0.9900
19:55641183:GG:G	donor_gain	0.9900
19:55641183:GGTA:G	donor_loss	0.9900
19:55641184:G:GC	donor_loss	0.9900
19:55641184:G:GG	donor_gain	0.9900
19:55641185:T:A	donor_loss	0.9900
19:55641249:G:T	donor_gain	0.9900
19:55642488:C:A	acceptor_gain	0.9900
19:55642495:A:AG	acceptor_gain	0.9900
19:55642496:G:GG	acceptor_gain	0.9900
19:55642496:GCT:G	acceptor_gain	0.9900
19:55635632:A:G	donor_gain	0.9800
19:55640125:GCT:G	acceptor_gain	0.9800
19:55641122:G:GT	donor_gain	0.9800
19:55641249:G:GT	donor_gain	0.9800
19:55642485:C:CA	acceptor_gain	0.9800
19:55642495:AGCT:A	acceptor_gain	0.9800
19:55642496:G:GA	acceptor_loss	0.9800
19:55642496:GC:G	acceptor_gain	0.9800

AlphaMissense

1271 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:55644941:T:C	F124L	1.000
19:55644943:C:A	F124L	1.000
19:55644943:C:G	F124L	1.000
19:55645115:T:C	F182L	1.000
19:55645117:T:A	F182L	1.000
19:55645117:T:G	F182L	1.000
19:55644857:T:A	F96I	0.999
19:55644857:T:C	F96L	0.999
19:55644859:C:A	F96L	0.999
19:55644859:C:G	F96L	0.999
19:55644876:T:C	L102P	0.999
19:55644884:C:A	H105N	0.999
19:55644884:C:G	H105D	0.999
19:55644886:C:A	H105Q	0.999
19:55644886:C:G	H105Q	0.999
19:55644898:C:A	H109Q	0.999
19:55644898:C:G	H109Q	0.999
19:55644914:T:C	F115L	0.999
19:55644916:C:A	F115L	0.999
19:55644916:C:G	F115L	0.999
19:55644920:T:C	C117R	0.999
19:55644930:G:A	C120Y	0.999
19:55644941:T:A	F124I	0.999
19:55644942:T:C	F124S	0.999
19:55644968:C:A	H133N	0.999
19:55645031:T:C	F154L	0.999
19:55645033:C:A	F154L	0.999
19:55645033:C:G	F154L	0.999
19:55645094:T:C	C175R	0.999
19:55645116:T:C	F182S	0.999

dbSNP variants (sampled 300 via entrez): RS1000077102 (19:55636294 G>A), RS1000112651 (19:55641738 G>A), RS1000309984 (19:55638962 C>T), RS1000340668 (19:55644460 C>A,T), RS1000373375 (19:55644206 G>A), RS1000552710 (19:55636543 A>G), RS1000683479 (19:55639217 C>T), RS1000720185 (19:55633292 A>G), RS1001076803 (19:55645534 G>A), RS1001159281 (19:55635308 T>A), RS1001170466 (19:55644564 C>T), RS1001512786 (19:55642941 C>A,G), RS1001617916 (19:55642640 GC>G), RS1001687946 (19:55639906 C>A,T), RS1002134977 (19:55643627 C>G,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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
afuresertib	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cupric chloride	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	affects expression	1
monomethylarsonous acid	increases expression	1
K 7174	increases expression	1
dimethylarsinous acid	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Carbamazepine	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diuron	decreases expression	1
Hydrogen Peroxide	affects expression	1
Niclosamide	increases expression	1
Ozone	increases abundance, affects expression	1
Quercetin	increases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Vincristine	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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