ZNF8

Summary

ZNF8 (zinc finger protein 8, HGNC:13154) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger protein 8 (P17098). Transcriptional repressor.

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 negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within BMP signaling pathway. Predicted to be active in nucleus.

Source: NCBI Gene 7554 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_021089

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13154
Approved symbol	ZNF8
Name	zinc finger protein 8
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	HF.18, Zfp128
Ensembl gene	ENSG00000278129
Ensembl biotype	protein_coding
OMIM	194532
Entrez	7554

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000621650, ENST00000914383

RefSeq mRNA: 1 — MANE Select: NM_021089 NM_021089

CCDS: CCDS12974

Canonical transcript exons

ENST00000621650 — 4 exons

Exon	Start	End
ENSE00001337661	58278955	58279147
ENSE00003717446	58286110	58286205
ENSE00003723656	58294098	58302791
ENSE00003726946	58285717	58285843

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 84.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0360 / max 64.1693, expressed in 1733 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177823	7.7691	1729
177824	0.2669	126

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	84.05	gold quality
cortical plate	UBERON:0005343	80.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.31	gold quality
ganglionic eminence	UBERON:0004023	79.27	gold quality
ventricular zone	UBERON:0003053	76.78	gold quality
caput epididymis	UBERON:0004358	75.91	gold quality
cauda epididymis	UBERON:0004360	75.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.52	gold quality
corpus epididymis	UBERON:0004359	75.30	gold quality
cartilage tissue	UBERON:0002418	74.18	gold quality
stromal cell of endometrium	CL:0002255	73.91	gold quality
pigmented layer of retina	UBERON:0001782	73.86	gold quality
sperm	CL:0000019	72.72	silver quality
tibia	UBERON:0000979	72.24	silver quality
Brodmann (1909) area 23	UBERON:0013554	72.08	silver quality
embryo	UBERON:0000922	72.01	gold quality
middle temporal gyrus	UBERON:0002771	71.54	gold quality
male germ cell	CL:0000015	71.35	silver quality
germinal epithelium of ovary	UBERON:0001304	70.93	gold quality
pancreatic ductal cell	CL:0002079	70.47	silver quality
bronchial epithelial cell	CL:0002328	70.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	70.41	gold quality
primary visual cortex	UBERON:0002436	70.33	gold quality
cerebellar cortex	UBERON:0002129	70.31	gold quality
cerebellar hemisphere	UBERON:0002245	70.22	gold quality
endothelial cell	CL:0000115	70.19	gold quality
cerebellum	UBERON:0002037	70.14	gold quality
colonic epithelium	UBERON:0000397	70.12	gold quality
entorhinal cortex	UBERON:0002728	70.05	gold quality
trabecular bone tissue	UBERON:0002483	69.45	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.41

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BMP1	Repression
TGFB1	Repression

JASPAR motifs

Motif	Name	Family
MA1718.1	ZNF8	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:28273063

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

12 targeting ZNF8, 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-4533	100.00	69.48	2758
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-9898	99.00	67.89	500
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-6769A-5P	97.99	64.16	851

Literature-anchored findings (GeneRIF, showing 3)

• ZNF8-miR-552-5p Axis Modulates ACSL4-Mediated Ferroptosis in Hepatocellular Carcinoma. (PMID:37126948)
• ZNF8 promotes progression of gastrointestinal cancers via a p53-dependent mechanism. (PMID:39173856)
• ZNF8 Orchestrates with Smad3 to Promote Lung Metastasis by Recruiting SMYD3 in Breast Cancer. (PMID:39225541)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp128	ENSMUSG00000060397
rattus_norvegicus	LOC108348304	ENSRNOG00000031459

Paralogs (38): ZFX (ENSG00000005889), ZBTB11 (ENSG00000066422), ZFAT (ENSG00000066827), ZFY (ENSG00000067646), ZNF586 (ENSG00000083828), IKZF5 (ENSG00000095574), ZNF419 (ENSG00000105136), ZNF549 (ENSG00000121406), ZSCAN20 (ENSG00000121903), ZNF304 (ENSG00000131845), PRDM15 (ENSG00000141956), ZNF660 (ENSG00000144792), ZNF711 (ENSG00000147180), ZNF773 (ENSG00000152439), ZNF256 (ENSG00000152454), ZNF837 (ENSG00000152475), ZNF691 (ENSG00000164011), ZNF610 (ENSG00000167554), E4F1 (ENSG00000167967), ZNF562 (ENSG00000171466), ZNF561 (ENSG00000171469), ZNF584 (ENSG00000171574), ZIK1 (ENSG00000171649), ZNF570 (ENSG00000171827), ZSCAN2 (ENSG00000176371), ZNF552 (ENSG00000178935), ZNF154 (ENSG00000179909), ZNF792 (ENSG00000180884), ZNF793 (ENSG00000188227), ZNF548 (ENSG00000188785), ZNF79 (ENSG00000196152), ZNF418 (ENSG00000196724), ZNF772 (ENSG00000197128), ZNF583 (ENSG00000198440), ZNF480 (ENSG00000198464), ZNF551 (ENSG00000204519), ZNF134 (ENSG00000213762), ZNF587B (ENSG00000269343)

Protein

Protein identifiers

Zinc finger protein 8 — P17098 (reviewed: P17098)

Alternative names: Zinc finger protein HF.18

All UniProt accessions (1): P17098

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. May modulate BMP and TGF-beta signal transduction, through its interaction with SMAD proteins.

Subunit / interactions. Interacts with SMAD1 (via MH1 and MH2 domains). Interacts with SMAD5. Interacts weakly with SMAD2. Interacts weakly with SMAD3 and SMAD4.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously present in many human cell lines of different embryological derivation.

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

RefSeq proteins (1): NP_066575* (*=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

UniProt features (22 total): zinc finger region 7, cross-link 4, region of interest 3, compositionally biased region 3, sequence conflict 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17098-F1	58.52	0.03

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 (4): 174, 249, 441, 545

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, GCM_MYCL1, GCM_RING1, GCM_FCGR2B, GCM_DPF2, WTGAAAT_UNKNOWN, GCM_TEC, GCM_CDH5, KAYO_AGING_MUSCLE_UP, GCM_LTK, GCM_BECN1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GCM_BNIP1, VERHAAK_GLIOBLASTOMA_CLASSICAL

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), BMP signaling pathway (GO:0030509), 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), 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 transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	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
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF8	ZNF385B	Q569K4	488
ZNF8	ZNF827	Q17R98	473
ZNF8	GARIN6	Q8NEG0	467
ZNF8	TSHZ3	Q63HK5	464
ZNF8	HORMAD2	Q8N7B1	402
ZNF8	A0A0U1RQV1	A0A0U1RQV1	373
ZNF8	HORMAD1	Q86X24	362
ZNF8	RSPRY1	Q96DX4	359
ZNF8	ZBTB3	Q9H5J0	354
ZNF8	EWSR1	Q01844	352
ZNF8	MSH3	P20585	349
ZNF8	LIMS3	P0CW19	349
ZNF8	ERVFRD-1	P60508	349
ZNF8	MSH6	P52701	348
ZNF8	FBLN2	P98095	333

IntAct

31 interactions, top by confidence:

A	B	Type	Score
ZNF8	TRIM28	psi-mi:“MI:0914”(association)	0.730
ZNF8	AP1M1	psi-mi:“MI:0915”(physical association)	0.560
ZNF8	ZNF114	psi-mi:“MI:0915”(physical association)	0.560
ZNF8	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530
TIMM50	ZNF724	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
Trim28	FTH1	psi-mi:“MI:0915”(physical association)	0.400
CBX5	ZNF568	psi-mi:“MI:0914”(association)	0.350
CBX3	KPNA4	psi-mi:“MI:0914”(association)	0.350
ZNF8	TRIM24	psi-mi:“MI:0914”(association)	0.350
WEE1	ZNF316	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MED19	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
FBLN2	ZNF316	psi-mi:“MI:0914”(association)	0.350
KCNA4	POLRMT	psi-mi:“MI:0914”(association)	0.350
PTX3	POLRMT	psi-mi:“MI:0914”(association)	0.350
ZNF8	METTL15	psi-mi:“MI:0914”(association)	0.350
PTX3	OFD1	psi-mi:“MI:0914”(association)	0.350
ZNF8	NFX1	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
AP1M1	ZNF8	psi-mi:“MI:0915”(physical association)	0.000
ZNF114	ZNF8	psi-mi:“MI:0915”(physical association)	0.000
MCRS1	ZNF8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (80): ZNF8 (Affinity Capture-RNA), ZNF8 (Affinity Capture-RNA), ZNF8 (Proximity Label-MS), ZNF8 (Affinity Capture-MS), ZNF8 (Affinity Capture-RNA), ZNF8 (Two-hybrid), ZNF8 (Two-hybrid), ZNF8 (Two-hybrid), ZNF8 (Affinity Capture-MS), ZNF8 (Positive Genetic), ZNF8 (Proximity Label-MS), ZNF8 (Proximity Label-MS), ZNF8 (Proximity Label-MS), ZNF8 (Affinity Capture-MS), ZNF8 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P9, A2AVR2, A6QPT6, B2KFW1, O14978, P17029, P17040, P17098, P25233, P70503, Q13342, Q14D33, Q3SYK4, Q3V3Q4, Q4KLI1, Q4R8H9, Q4V8E9, Q5PPP4, Q5R670, Q5R7U0, Q5VWK0, Q61066, Q63HK3, Q68CQ1, Q6PCZ4, Q7TS72, Q80ZG2, Q8BGS3, Q8CF60, Q8IWY8, Q8N660, Q8NDZ0, Q8TD17, Q921B4, Q923B3, Q96D09, Q96GC6, Q96JL9, Q96M43, Q99608

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

955 predictions. Top by Δscore:

Variant	Effect	Δscore
19:58285713:TCAGG:T	acceptor_loss	1.0000
19:58285714:CAG:C	acceptor_loss	1.0000
19:58285714:CAGG:C	acceptor_loss	1.0000
19:58285715:A:AG	acceptor_gain	1.0000
19:58285715:AGGA:A	acceptor_loss	1.0000
19:58285716:G:GC	acceptor_loss	1.0000
19:58285716:G:GG	acceptor_gain	1.0000
19:58285840:ATAGG:A	donor_gain	1.0000
19:58285841:TAGG:T	donor_gain	1.0000
19:58285841:TAGGT:T	donor_gain	1.0000
19:58285842:AGGTA:A	donor_gain	1.0000
19:58285843:GGTAA:G	donor_gain	1.0000
19:58285844:G:C	donor_gain	1.0000
19:58285844:G:GA	donor_gain	1.0000
19:58285844:G:GG	donor_gain	1.0000
19:58285845:T:A	donor_gain	1.0000
19:58286102:A:AG	acceptor_gain	1.0000
19:58286103:T:G	acceptor_gain	1.0000
19:58286105:TCCA:T	acceptor_loss	1.0000
19:58286106:CCAG:C	acceptor_loss	1.0000
19:58286107:CAG:C	acceptor_loss	1.0000
19:58286107:CAGG:C	acceptor_loss	1.0000
19:58286108:A:AG	acceptor_gain	1.0000
19:58286108:A:T	acceptor_loss	1.0000
19:58286108:AG:A	acceptor_gain	1.0000
19:58286108:AGGTC:A	acceptor_loss	1.0000
19:58286109:G:GG	acceptor_gain	1.0000
19:58286109:G:GT	acceptor_gain	1.0000
19:58286109:GG:G	acceptor_gain	1.0000
19:58286109:GGT:G	acceptor_gain	1.0000

AlphaMissense

3808 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:58294688:T:C	F294L	1.000
19:58294690:C:A	F294L	1.000
19:58294690:C:G	F294L	1.000
19:58294772:T:C	F322L	1.000
19:58294774:C:A	F322L	1.000
19:58294774:C:G	F322L	1.000
19:58294856:T:C	F350L	1.000
19:58294858:C:A	F350L	1.000
19:58294858:C:G	F350L	1.000
19:58294940:T:C	F378L	1.000
19:58294942:C:A	F378L	1.000
19:58294942:C:G	F378L	1.000
19:58294604:T:C	F266L	0.999
19:58294605:T:C	F266S	0.999
19:58294606:T:A	F266L	0.999
19:58294606:T:G	F266L	0.999
19:58294623:T:C	L272P	0.999
19:58294631:C:G	H275D	0.999
19:58294689:T:C	F294S	0.999
19:58294715:C:G	H303D	0.999
19:58294717:T:A	H303Q	0.999
19:58294717:T:G	H303Q	0.999
19:58294722:G:C	R305P	0.999
19:58294773:T:C	F322S	0.999
19:58294791:T:C	L328P	0.999
19:58294799:C:G	H331D	0.999
19:58294807:G:C	R333S	0.999
19:58294807:G:T	R333S	0.999
19:58294857:T:C	F350S	0.999
19:58294883:C:G	H359D	0.999

dbSNP variants (sampled 300 via entrez): RS1000019488 (19:58286804 G>A), RS1000169333 (19:58298315 C>A), RS1000233911 (19:58290822 G>A), RS1000256372 (19:58284205 C>T), RS1000280390 (19:58293444 G>A), RS1000289380 (19:58277760 A>G), RS1000306615 (19:58278092 C>G,T), RS1000379856 (19:58278451 C>T), RS1000456361 (19:58302012 T>C), RS1000665813 (19:58296404 G>C,T), RS1000691701 (19:58284020 C>T), RS1000909682 (19:58299468 C>G), RS1001015180 (19:58296240 A>G), RS1001057067 (19:58283720 C>T), RS1001183876 (19:58299405 C>T)

Disease associations

OMIM: gene MIM:194532 | 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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric oxide	increases expression	1
resorcinol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Leflunomide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	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_HD44	HEK293 eGFP-ZNF8	Transformed cell line	Female

Clinical trials (associated diseases)

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