ZNF382

Summary

ZNF382 (zinc finger protein 382, HGNC:17409) is a protein-coding gene on chromosome 19q13.12, encoding Zinc finger protein 382 (Q96SR6). Functions as a sequence-specific transcriptional repressor.

This gene encodes a KRAB domain zinc finger transcription factor (KZNF). KZNFs play critical roles in the regulation of many cellular processes including differentiation, proliferation and apoptosis. The encoded protein inhibits activating protein 1 (AP-1) and nuclear factor kappa-B (NF-kB) signaling and may function as a tumor suppressor in multiple carcinomas. This gene is found in a cluster with other zinc finger protein genes on the long arm of chromosome 19, and alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 84911 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 71 total
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_032825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17409
Approved symbol	ZNF382
Name	zinc finger protein 382
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14686, KS1
Ensembl gene	ENSG00000161298
Ensembl biotype	protein_coding
OMIM	609516
Entrez	84911

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000292928, ENST00000423582, ENST00000435416, ENST00000439428, ENST00000460384, ENST00000460670, ENST00000463910, ENST00000585467, ENST00000590785, ENST00000884594, ENST00000884595, ENST00000884596, ENST00000949445, ENST00000949446

RefSeq mRNA: 5 — MANE Select: NM_032825 NM_001256838, NM_001398490, NM_001398491, NM_001398492, NM_032825

CCDS: CCDS33004, CCDS58659

Canonical transcript exons

ENST00000292928 — 5 exons

Exon	Start	End
ENSE00001150836	36609902	36610053
ENSE00001862679	36605313	36605347
ENSE00001947359	36626130	36634114
ENSE00003476217	36607552	36607622
ENSE00003650857	36610650	36610742

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 90.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.3109 / max 72.8318, expressed in 1132 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175522	3.1417	1112
175521	0.1692	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	90.26	gold quality
cerebellar hemisphere	UBERON:0002245	89.35	gold quality
cerebellar cortex	UBERON:0002129	89.18	gold quality
cerebellum	UBERON:0002037	87.26	gold quality
cortical plate	UBERON:0005343	85.20	gold quality
oviduct epithelium	UBERON:0004804	82.09	gold quality
ganglionic eminence	UBERON:0004023	81.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.01	gold quality
right frontal lobe	UBERON:0002810	79.93	gold quality
secondary oocyte	CL:0000655	79.78	gold quality
ventricular zone	UBERON:0003053	79.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.59	gold quality
adrenal tissue	UBERON:0018303	77.34	gold quality
endothelial cell	CL:0000115	77.16	silver quality
right uterine tube	UBERON:0001302	76.92	gold quality
prefrontal cortex	UBERON:0000451	76.28	gold quality
anterior cingulate cortex	UBERON:0009835	76.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.52	gold quality
neocortex	UBERON:0001950	75.41	gold quality
primary visual cortex	UBERON:0002436	75.15	gold quality
frontal cortex	UBERON:0001870	75.05	gold quality
apex of heart	UBERON:0002098	74.14	gold quality
pituitary gland	UBERON:0000007	74.00	gold quality
adenohypophysis	UBERON:0002196	73.91	gold quality
Brodmann (1909) area 23	UBERON:0013554	73.89	silver quality
heart left ventricle	UBERON:0002084	73.86	gold quality
islet of Langerhans	UBERON:0000006	73.73	gold quality
cerebral cortex	UBERON:0000956	73.34	gold quality
cardiac ventricle	UBERON:0002082	73.28	gold quality
brain	UBERON:0000955	73.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	6.30

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
CDK6	Repression
CXCL14
HMGA2	Repression
ID1	Repression
IKBKE	Repression
JUN	Repression
MITF	Repression
MYC	Repression
NFKB1	Repression
STAT3	Repression
STAT5B	Repression

JASPAR motifs

Motif	Name	Family
MA1594.1	ZNF382	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:27852650

Upstream regulators (CollecTRI, top): JUN, TET1

miRNA regulators (miRDB)

81 targeting ZNF382, 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-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734

Literature-anchored findings (GeneRIF, showing 10)

• mapped to chromosome 19q13.13; transcript specific for ZNF382 is expressed at very early embryonic stage; at the adult stage, ZNF382 expression is restricted largely to heart tissue (PMID:12459182)
• ZNF382 is a functional tumor suppressor frequently methylated in multiple carcinomas. (PMID:20682794)
• Expression of MAGE I proteins, MAGE-A3 or MAGE-C2, relieved repression of a reporter gene by ZNF382 and MAGE I expression relieved KAP1 mediated ID1 repression. (PMID:21876767)
• Methylation changes of GFRA1, SRF, and ZNF382 may be a potential biomarker set for prediction of gastric carcinoma metastasis. (PMID:25009298)
• Data suggests that zinc finger protein 382 (ZNF382) may be considered a putative tumor suppressor gene in pediatric acute myeloid leukemia (AML). (PMID:25319049)
• findings demonstrate that ZNF382 functions as a bona fide tumour suppressor inhibiting oesophageal squamous cell carcinoma pathogenesis through inhibiting the Wnt/beta-catenin signalling pathway. (PMID:29760376)
• Study suggests that ZNF382 functions as a tumor suppressor in gastric cancer (GC) cells, but is frequently methylated in both GC cell lines and primary gastric tumors. (PMID:29956735)
• ZNF382 acts as a tumor suppressor, and is co-regulated by HBx and epigenetic mechanism in Hepatitis B virus-related hepatocellular carcinogenesis. (PMID:30804458)
• ZNF382 is downregulated in multiple tumors due to hypermethylation of its promoter (PMID:31678273)
• A Three Protein-Coding Gene Prognostic Model Predicts Overall Survival in Bladder Cancer Patients. (PMID:33150179)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp382	ENSMUSG00000074220
rattus_norvegicus	Zfp382	ENSRNOG00000020777
drosophila_melanogaster	CG14442	FBGN0029893
drosophila_melanogaster	CG14440	FBGN0029894

Paralogs (11): IKZF2 (ENSG00000030419), ZNF821 (ENSG00000102984), ZNF639 (ENSG00000121864), IKZF4 (ENSG00000123411), IKZF3 (ENSG00000161405), ZNF613 (ENSG00000176024), IKZF1 (ENSG00000185811), ZNF567 (ENSG00000189042), ZNF649 (ENSG00000198093), ZNF564 (ENSG00000249709), ZNF350 (ENSG00000256683)

Protein

Protein identifiers

Zinc finger protein 382 — Q96SR6 (reviewed: Q96SR6)

Alternative names: KRAB/zinc finger suppressor protein 1, Multiple zinc finger and krueppel-associated box protein KS1

All UniProt accessions (4): C9JME7, Q96SR6, K7EK67, K7EQ52

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a sequence-specific transcriptional repressor.

Subunit / interactions. Interacts with TRIM28; enhances the transcriptional repressor activity.

Subcellular location. Nucleus.

Tissue specificity. Specifically expressed in heart with a weaker expression also detected in skeletal muscle.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q96SR6-1	1	yes
Q96SR6-2	2
Q96SR6-3	3

RefSeq proteins (5): NP_001243767, NP_001385419, NP_001385420, NP_001385421, NP_116214* (*=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 (21 total): zinc finger region 10, region of interest 4, splice variant 2, sequence conflict 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SR6-F1	62.60	0.23

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins

MSigDB gene sets: 63 (showing top): TGCGCANK_UNKNOWN, AGGAGTG_MIR483, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, FOXN3_TARGET_GENES, OVOL3_TARGET_GENES, RYBP_TARGET_GENES, ZIM3_TARGET_GENES, ZNF22_TARGET_GENES, ZNF274_TARGET_GENES, ZNF30_TARGET_GENES, ZNF391_TARGET_GENES, ZNF524_TARGET_GENES, ZNF563_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 (5): 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), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Regulation of endogenous retroelements	1

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
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	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
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF382	TRIM28	Q13263	902
ZNF382	DVL2	O14641	528
ZNF382	ZNF280A	P59817	511
ZNF382	FZD1	Q9UP38	505
ZNF382	CCDC61	Q9Y6R9	458
ZNF382	CBX1	P23197	457
ZNF382	ZNF84	P51523	455
ZNF382	ZNF200	P98182	453
ZNF382	ZNF668	Q96K58	453
ZNF382	JUN	P05412	446
ZNF382	ERGIC2	Q96RQ1	442
ZNF382	HRAS	P01112	436
ZNF382	FOS	P01100	423
ZNF382	ZNF324	O75467	400
ZNF382	GIPC2	Q8TF65	396

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ZNF382	IPO8	psi-mi:“MI:0914”(association)	0.530
BRAP	ZNF382	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (10): ZNF382 (Two-hybrid), CCDC50 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), IPO8 (Affinity Capture-MS), GTF2IRD1 (Affinity Capture-MS), MLLT4 (Affinity Capture-MS), ZNF382 (Proximity Label-MS), CBX1 (Affinity Capture-Western), TRIM28 (Reconstituted Complex), TRIM28 (Affinity Capture-Western)

ESM2 similar proteins: A0A1W2PQL4, A0JPL0, A2RRD8, A6NHJ4, A6NP11, B4DX44, O75346, O95780, P0CB33, P21506, P51508, P52738, Q0D2J5, Q0VGE8, Q12901, Q13360, Q14593, Q15973, Q2M218, Q2M3X9, Q2VY69, Q3SXZ3, Q5HY98, Q5RCJ2, Q5VIY5, Q6J6I6, Q7L2R6, Q86XU0, Q86Y25, Q8IW36, Q8IYN0, Q8IYX0, Q8N782, Q8N883, Q8N9Z0, Q8NDP4, Q95K49, Q969W8, Q96H40, Q96N58

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

1 interactions.

A	Effect	B	Mechanism
TET1	“up-regulates quantity by expression”	ZNF382	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1321 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36609454:T:G	acceptor_gain	1.0000
19:36610648:AG:A	acceptor_gain	1.0000
19:36610649:GG:G	acceptor_gain	1.0000
19:36605417:G:GT	donor_gain	0.9900
19:36605444:G:T	donor_gain	0.9900
19:36605484:G:GT	donor_gain	0.9900
19:36605517:GATCT:G	donor_gain	0.9900
19:36605522:G:GG	donor_gain	0.9900
19:36607551:GGACT:G	acceptor_gain	0.9900
19:36607618:CTCAG:C	donor_loss	0.9900
19:36607619:TCAG:T	donor_loss	0.9900
19:36607620:CAGGT:C	donor_loss	0.9900
19:36607621:AGGT:A	donor_loss	0.9900
19:36607622:GG:G	donor_loss	0.9900
19:36607623:G:T	donor_loss	0.9900
19:36607624:T:G	donor_loss	0.9900
19:36610014:G:T	donor_gain	0.9900
19:36610049:TGTGG:T	donor_loss	0.9900
19:36610050:GTGG:G	donor_gain	0.9900
19:36610052:GG:G	donor_gain	0.9900
19:36610052:GGGTA:G	donor_loss	0.9900
19:36610053:GG:G	donor_gain	0.9900
19:36610054:G:GG	donor_gain	0.9900
19:36610054:GTAA:G	donor_loss	0.9900
19:36610055:T:C	donor_loss	0.9900
19:36610645:ATCAG:A	acceptor_gain	0.9900
19:36610647:CAGGG:C	acceptor_loss	0.9900
19:36610648:A:T	acceptor_loss	0.9900
19:36610649:G:GT	acceptor_loss	0.9900
19:36610739:CTAGG:C	donor_loss	0.9900

AlphaMissense

3690 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:36626978:T:C	F361L	1.000
19:36626980:C:A	F361L	1.000
19:36626980:C:G	F361L	1.000
19:36627146:T:C	F417L	1.000
19:36627148:T:A	F417L	1.000
19:36627148:T:G	F417L	1.000
19:36626894:T:C	F333L	0.999
19:36626895:T:C	F333S	0.999
19:36626896:C:A	F333L	0.999
19:36626896:C:G	F333L	0.999
19:36627062:T:C	F389L	0.999
19:36627064:T:A	F389L	0.999
19:36627064:T:G	F389L	0.999
19:36627081:T:C	L395P	0.999
19:36627165:T:C	L423P	0.999
19:36627230:T:C	F445L	0.999
19:36627232:C:A	F445L	0.999
19:36627232:C:G	F445L	0.999
19:36627249:T:C	L451P	0.999
19:36627314:T:C	F473L	0.999
19:36627316:C:A	F473L	0.999
19:36627316:C:G	F473L	0.999
19:36627398:T:C	F501L	0.999
19:36627400:C:A	F501L	0.999
19:36627400:C:G	F501L	0.999
19:36626844:G:C	R316P	0.998
19:36626873:T:C	C326R	0.998
19:36626913:T:C	L339P	0.998
19:36626979:T:C	F361S	0.998
19:36626997:T:C	L367P	0.998

dbSNP variants (sampled 300 via entrez): RS1000181299 (19:36626625 A>G), RS1000184853 (19:36606121 T>G), RS1000237346 (19:36605881 T>C), RS1000262998 (19:36634344 G>A), RS1000539433 (19:36612706 A>G), RS1000658389 (19:36631095 C>T), RS1000705152 (19:36607192 A>G), RS1000710126 (19:36631370 A>C,G), RS1000908996 (19:36617893 A>G), RS1001076700 (19:36606911 C>G), RS1001139638 (19:36611310 T>G), RS1001182567 (19:36604709 A>T), RS1001232086 (19:36607524 C>T), RS1001233194 (19:36604395 T>C), RS1001466496 (19:36611027 C>A,G)

Disease associations

OMIM: gene MIM:609516 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
Decitabine	decreases reaction, decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	decreases expression	1
Smoke	decreases expression, decreases reaction, increases expression	1
T-2 Toxin	increases expression	1
Aflatoxin B1	decreases expression	1
Gold Compounds	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8G8	SEES3-1V human ZNF382, clone1	Embryonic stem cell	Male
CVCL_A8G9	SEES3-1V human ZNF382, clone2	Embryonic stem cell	Male
CVCL_A8H0	SEES3-1V human ZNF382, clone3	Embryonic stem cell	Male
CVCL_XW39	HEK293 eGFP-ZNF382	Transformed cell line	Female

Clinical trials (associated diseases)

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