ZNF468

Summary

ZNF468 (zinc finger protein 468, HGNC:33105) is a protein-coding gene on chromosome 19q13.41, encoding Zinc finger protein 468 (Q5VIY5). 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 active in nucleus.

Source: NCBI Gene 90333 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_001008801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33105
Approved symbol	ZNF468
Name	zinc finger protein 468
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204604
Ensembl biotype	protein_coding
OMIM	616841
Entrez	90333

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 nonsense_mediated_decay

ENST00000243639, ENST00000595646, ENST00000597924, ENST00000601847, ENST00000601980, ENST00000602144, ENST00000956998

RefSeq mRNA: 2 — MANE Select: NM_001008801 NM_001008801, NM_001277120

CCDS: CCDS33094, CCDS62781

Canonical transcript exons

ENST00000595646 — 4 exons

Exon	Start	End
ENSE00003096409	52857572	52857619
ENSE00003224390	52838010	52842151
ENSE00003625476	52849087	52849213
ENSE00003644211	52854258	52854345

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 89.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.1086 / max 51.8163, expressed in 1236 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182536	3.1086	1236

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	89.35	gold quality
placenta	UBERON:0001987	88.09	gold quality
secondary oocyte	CL:0000655	87.73	gold quality
germinal epithelium of ovary	UBERON:0001304	87.71	gold quality
islet of Langerhans	UBERON:0000006	86.13	gold quality
eye	UBERON:0000970	85.81	gold quality
epithelium of nasopharynx	UBERON:0001951	85.68	gold quality
nasopharynx	UBERON:0001728	85.67	gold quality
buccal mucosa cell	CL:0002336	84.90	silver quality
amniotic fluid	UBERON:0000173	84.82	gold quality
oocyte	CL:0000023	84.04	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.94	gold quality
colonic mucosa	UBERON:0000317	83.21	gold quality
parietal pleura	UBERON:0002400	82.92	gold quality
endometrium	UBERON:0001295	82.27	gold quality
pleura	UBERON:0000977	81.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.49	gold quality
adrenal tissue	UBERON:0018303	81.36	gold quality
visceral pleura	UBERON:0002401	81.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.74	gold quality
bronchial epithelial cell	CL:0002328	80.23	gold quality
cortical plate	UBERON:0005343	80.20	gold quality
rectum	UBERON:0001052	80.11	gold quality
mammary duct	UBERON:0001765	79.99	silver quality
esophagus squamous epithelium	UBERON:0006920	79.89	gold quality
pancreas	UBERON:0001264	79.73	gold quality
corpus epididymis	UBERON:0004359	79.52	gold quality
skin of hip	UBERON:0001554	78.77	gold quality
granulocyte	CL:0000094	78.19	gold quality
leukocyte	CL:0000738	78.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.46
E-GEOD-99795	no	151.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting ZNF468, 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-3925-3P	100.00	69.95	1237
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4803	99.98	71.99	3117
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-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 3)

• 2 splice variants ZNF468.1 and ZNF468.2 contain 11 C2H2-type zinc finger motifs at their C-termini. They are widely expressed in normal human tissues, except in heart and brain, and they are also co-expressional. (PMID:16144304)
• ZNF468 inhibits irradiation-induced G2/M cell cycle arrest and apoptosis by facilitating AURKA transcription in Esophageal Squamous Cell Carcinoma. (PMID:38368674)
• ZNF468-mediated epigenetic upregulation of VEGF-C facilitates lymphangiogenesis and lymphatic metastasis in ESCC via PI3K/Akt and ERK1/2 signaling pathways. (PMID:39141315)

Cross-species orthologs

0 orthologs

Paralogs (11): ZNF761 (ENSG00000160336), ZNF701 (ENSG00000167562), ZNF816 (ENSG00000180257), ZNF766 (ENSG00000196214), ZNF765 (ENSG00000196417), ZNF860 (ENSG00000197385), ZNF813 (ENSG00000198346), ZNF525 (ENSG00000203326), ZNF888 (ENSG00000213793), ZNF578 (ENSG00000258405), (ENSG00000269825)

Protein

Protein identifiers

Zinc finger protein 468 — Q5VIY5 (reviewed: Q5VIY5)

All UniProt accessions (5): M0QYC0, M0QYE7, M0QZR5, M0R171, Q5VIY5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Isoform 1 and isoform 2 are highly expressed in placenta, pancreas, and small intestine. Lower expression in colon, ovary, testis, prostate, thymus, spleen, kidney, and liver. No expression detected in heart and brain.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VIY5-1	1, ZNF468.1	yes
Q5VIY5-2	2, ZNF468.2

RefSeq proteins (2): NP_001008801, NP_001264049 (=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
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF01352, PF13465

UniProt features (18 total): zinc finger region 11, sequence variant 2, sequence conflict 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VIY5-F1	65.57	0.26

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 96 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, WEI_MYCN_TARGETS_WITH_E_BOX, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, CHEN_HOXA5_TARGETS_9HR_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, JOHNSTONE_PARVB_TARGETS_2_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ELF2_TARGET_GENES, ZBTB12_TARGET_GENES, MIR548AJ_3P_MIR548X_3P, MIR548AE_3P_MIR548AQ_3P

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), negative regulation of macromolecule biosynthetic process (GO:0010558)

GO Molecular Function (5): 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), 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 macromolecule biosynthetic process	2
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
gene expression	1
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
negative regulation of macromolecule metabolic 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
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF468	KRTAP9-2	Q9BYQ4	444
ZNF468	TFE3	P19532	428
ZNF468	SUGT1	Q9Y2Z0	347
ZNF468	WWC3	Q9ULE0	336
ZNF468	SRP9	P49458	330
ZNF468	RPS6KC1	Q96S38	324
ZNF468	MACIR	Q96GV9	323
ZNF468	MINPP1	Q9UNW1	322
ZNF468	MBTD1	Q05BQ5	304
ZNF468	GLMN	Q92990	298
ZNF468	ALG8	Q9BVK2	272
ZNF468	SETDB1	Q15047	255
ZNF468	EEF1AKMT2	Q5JPI9	253
ZNF468	TRIM28	Q13263	239
ZNF468	PAFAH1B3	Q15102	239

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
BMP2K	ZNF468	psi-mi:“MI:0915”(physical association)	0.370
ZNF468	NHERF1	psi-mi:“MI:0915”(physical association)	0.370
AATF	ZNF468	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (8): ZNF468 (Affinity Capture-MS), ZNF468 (Affinity Capture-MS), ZNF468 (Affinity Capture-MS), ZNF468 (Affinity Capture-MS), ZNF468 (Affinity Capture-MS), ZNF468 (Affinity Capture-RNA), ZNF468 (Two-hybrid), ZNF468 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

886 predictions. Top by Δscore:

Variant	Effect	Δscore
19:52849081:CCTCA:C	donor_loss	1.0000
19:52849082:CTCAC:C	donor_loss	1.0000
19:52849083:TCA:T	donor_loss	1.0000
19:52849084:CA:C	donor_loss	1.0000
19:52849085:AC:A	donor_gain	1.0000
19:52849086:CC:C	donor_gain	1.0000
19:52849126:C:A	donor_gain	1.0000
19:52849210:GACC:G	acceptor_gain	1.0000
19:52849211:ACCC:A	acceptor_loss	1.0000
19:52849212:CC:C	acceptor_gain	1.0000
19:52849213:CC:C	acceptor_gain	1.0000
19:52849213:CCTGA:C	acceptor_loss	1.0000
19:52849214:C:A	acceptor_loss	1.0000
19:52854252:TCTCA:T	donor_loss	1.0000
19:52854253:CTCA:C	donor_loss	1.0000
19:52854254:TCA:T	donor_loss	1.0000
19:52854255:CA:C	donor_loss	1.0000
19:52854256:ACCTG:A	donor_loss	1.0000
19:52854257:C:A	donor_loss	1.0000
19:52854341:CAATC:C	acceptor_gain	1.0000
19:52854344:TCC:T	acceptor_loss	1.0000
19:52854346:C:CC	acceptor_gain	1.0000
19:52854346:CTG:C	acceptor_loss	1.0000
19:52854347:T:C	acceptor_loss	1.0000
19:52849079:AT:A	donor_gain	0.9900
19:52849085:A:AC	donor_gain	0.9900
19:52849086:C:CC	donor_gain	0.9900
19:52849209:AGACC:A	acceptor_gain	0.9900
19:52849214:C:CC	acceptor_gain	0.9900
19:52849219:A:AC	acceptor_gain	0.9900

AlphaMissense

3494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:52840950:G:C	F448L	0.995
19:52840950:G:T	F448L	0.995
19:52840952:A:G	F448L	0.995
19:52840782:G:C	F504L	0.994
19:52840782:G:T	F504L	0.994
19:52840784:A:G	F504L	0.994
19:52840866:G:C	F476L	0.994
19:52840866:G:T	F476L	0.994
19:52840868:A:G	F476L	0.994
19:52841034:G:C	F420L	0.994
19:52841034:G:T	F420L	0.994
19:52841036:A:G	F420L	0.994
19:52841118:G:C	F392L	0.992
19:52841118:G:T	F392L	0.992
19:52841120:A:G	F392L	0.992
19:52841370:G:C	F308L	0.989
19:52841370:G:T	F308L	0.989
19:52841372:A:G	F308L	0.989
19:52841202:A:C	F364L	0.988
19:52841202:A:T	F364L	0.988
19:52841204:A:G	F364L	0.988
19:52840849:A:G	L482P	0.986
19:52841029:C:G	R422P	0.986
19:52849178:G:C	F17L	0.986
19:52849178:G:T	F17L	0.986
19:52849180:A:G	F17L	0.986
19:52841454:A:C	F280L	0.985
19:52841454:A:T	F280L	0.985
19:52841456:A:G	F280L	0.985
19:52841286:G:C	F336L	0.984

dbSNP variants (sampled 300 via entrez): RS1000139315 (19:52839742 T>C), RS1000280717 (19:52859069 A>G), RS1000435756 (19:52854159 A>C,G), RS1000444926 (19:52839599 T>C), RS1000568923 (19:52859582 G>A), RS1000719259 (19:52858859 C>T), RS1000770548 (19:52855255 T>C), RS1000778194 (19:52850755 C>G,T), RS1000859836 (19:52845897 G>C), RS1001078671 (19:52846139 G>A), RS1001194756 (19:52847227 T>G), RS1001306375 (19:52851587 T>A), RS1001373339 (19:52850743 C>A,T), RS1001689843 (19:52840217 C>T), RS1002122427 (19:52840465 T>C)

Disease associations

OMIM: gene MIM:616841 | 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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases methylation	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
geraniol	increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Gallic Acid	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Nicotine	increases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1
Dronabinol	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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