ZNF398

Summary

ZNF398 (zinc finger protein 398, HGNC:18373) is a protein-coding gene on chromosome 7q36.1, encoding Zinc finger protein 398 (Q8TD17). Functions as a transcriptional activator.

This gene encodes a member of the Kruppel family of C2H2-type zinc-finger transcription factor proteins. The encoded protein acts as a transcriptional activator. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described, but their full length sequence has not been determined.

Source: NCBI Gene 57541 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_170686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18373
Approved symbol	ZNF398
Name	zinc finger protein 398
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	p71-ZER6, p52-ZER6, ZER6, KIAA1339, P51, P71
Ensembl gene	ENSG00000197024
Ensembl biotype	protein_coding
OMIM	618593
Entrez	57541

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000426851, ENST00000475153, ENST00000483892, ENST00000485111, ENST00000491174, ENST00000957024

RefSeq mRNA: 2 — MANE Select: NM_170686 NM_020781, NM_170686

CCDS: CCDS47739, CCDS5894

Canonical transcript exons

ENST00000475153 — 6 exons

Exon	Start	End
ENSE00001172268	149166817	149166930
ENSE00001361399	149176468	149176581
ENSE00001753514	149147453	149147766
ENSE00001896077	149178648	149183042
ENSE00003558494	149166158	149166284
ENSE00003674393	149153945	149154340

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 95.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1787 / max 371.8702, expressed in 1803 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81880	17.1900	1800
81881	1.1788	602
81876	0.8934	528
81878	0.5642	292
81879	0.3523	165

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	95.46	gold quality
endothelial cell	CL:0000115	90.66	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.78	gold quality
amniotic fluid	UBERON:0000173	88.46	gold quality
middle temporal gyrus	UBERON:0002771	87.54	gold quality
cerebellar vermis	UBERON:0004720	87.00	gold quality
palpebral conjunctiva	UBERON:0001812	86.75	gold quality
esophagus squamous epithelium	UBERON:0006920	86.56	gold quality
epithelial cell of pancreas	CL:0000083	86.44	silver quality
skin of hip	UBERON:0001554	84.84	gold quality
ileal mucosa	UBERON:0000331	84.67	gold quality
visceral pleura	UBERON:0002401	84.57	gold quality
gingival epithelium	UBERON:0001949	84.43	gold quality
upper arm skin	UBERON:0004263	84.35	gold quality
tibia	UBERON:0000979	84.22	gold quality
trabecular bone tissue	UBERON:0002483	84.17	gold quality
cortical plate	UBERON:0005343	84.08	gold quality
sperm	CL:0000019	83.50	gold quality
gingiva	UBERON:0001828	83.10	gold quality
tibialis anterior	UBERON:0001385	82.91	silver quality
parietal pleura	UBERON:0002400	82.51	gold quality
primary visual cortex	UBERON:0002436	81.86	gold quality
blood	UBERON:0000178	81.71	gold quality
bronchial epithelial cell	CL:0002328	81.61	gold quality
pigmented layer of retina	UBERON:0001782	81.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.02	gold quality
bronchus	UBERON:0002185	80.96	gold quality
upper leg skin	UBERON:0004262	80.91	gold quality
postcentral gyrus	UBERON:0002581	80.84	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	193.97
E-ANND-3	no	3.68
E-MTAB-5061	no	3.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CDKN2A
ZNF354C
ZNF398

Upstream regulators (CollecTRI, top): ESR1, NFKB2, STAT1, ZNF398

miRNA regulators (miRDB)

101 targeting ZNF398, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-7150	99.62	66.80	1322

Literature-anchored findings (GeneRIF, showing 1)

• The transcriptional regulator ZNF398 mediates pluripotency and epithelial character downstream of TGF-beta in human PSCs. (PMID:32398665)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp398	ENSMUSG00000062519
rattus_norvegicus	Zfp398	ENSRNOG00000006703

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391)

Protein

Protein identifiers

Zinc finger protein 398 — Q8TD17 (reviewed: Q8TD17)

Alternative names: Zinc finger DNA-binding protein p52/p71

All UniProt accessions (3): Q8TD17, A0A090N7S8, A0A090N8F2

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a transcriptional activator.

Subcellular location. Nucleus.

Induction. By estrogen receptor alpha.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TD17-1	1, p71	yes
Q8TD17-2	2, p52

RefSeq proteins (2): NP_065832, NP_733787* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR003655	aKRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF01352, PF13913

UniProt features (19 total): zinc finger region 9, region of interest 3, sequence variant 2, chain 1, domain 1, compositionally biased region 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD17-F1	61.20	0.19

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 (1): 265

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 135 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AP4_Q6, CAGCTG_AP4_Q5, GROSS_HYPOXIA_VIA_ELK3_DN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, OSMAN_BLADDER_CANCER_DN, HEB_Q6, BENPORATH_ES_1, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, LIU_PROSTATE_CANCER_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ATF6_TARGET_GENES

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (6): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), 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)

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
DNA-templated transcription	2
regulation of DNA-templated transcription	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
positive regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	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

987 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF398	DDX17	Q92841	807
ZNF398	ICA1	P78506	611
ZNF398	NKTR	P30414	511
ZNF398	POLDIP3	Q9BY77	507
ZNF398	MDM2	Q00987	464
ZNF398	MYL2	P10916	461
ZNF398	STRBP	Q96SI9	450
ZNF398	AP3M2	P53677	445
ZNF398	YPEL3	P61236	427
ZNF398	ACOT13	Q9NPJ3	421
ZNF398	PCMT1	P22061	418
ZNF398	UGGT2	Q9NYU1	414
ZNF398	TMBIM6	P55061	404
ZNF398	EMG1	Q92979	404
ZNF398	ZNF534	Q76KX8	402

IntAct

91 interactions, top by confidence:

A	B	Type	Score
ZNF398	ELMO1	psi-mi:“MI:0915”(physical association)	0.800
ELMO1	ZNF398	psi-mi:“MI:0915”(physical association)	0.800
ZNF398	MFAP1	psi-mi:“MI:0915”(physical association)	0.780
MFAP1	ZNF398	psi-mi:“MI:0915”(physical association)	0.780
ZNF783	ZNF398	psi-mi:“MI:0915”(physical association)	0.740
ZNF398	ZNF783	psi-mi:“MI:0915”(physical association)	0.740
ZNF398	CLK2	psi-mi:“MI:0915”(physical association)	0.720
ZNF398	MAGOHB	psi-mi:“MI:0915”(physical association)	0.720
ZNF398	CIB3	psi-mi:“MI:0915”(physical association)	0.720
MAGOHB	ZNF398	psi-mi:“MI:0915”(physical association)	0.720
CIB3	ZNF398	psi-mi:“MI:0915”(physical association)	0.720
CLK2	ZNF398	psi-mi:“MI:0915”(physical association)	0.720
ZNF398	ZNF282	psi-mi:“MI:0914”(association)	0.710
ZNF282	ZNF398	psi-mi:“MI:0915”(physical association)	0.710
GPATCH2L	ZNF398	psi-mi:“MI:0915”(physical association)	0.670
AIRIM	ZNF398	psi-mi:“MI:0915”(physical association)	0.670
ZNF398	GPATCH2L	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (62): ZNF398 (Two-hybrid), ZNF398 (Two-hybrid), ZNF398 (Two-hybrid), ZNF398 (Two-hybrid), ZNF398 (Two-hybrid), ZNF398 (Two-hybrid), ZNF398 (Two-hybrid), PLEKHF2 (Two-hybrid), CIB3 (Two-hybrid), LOC155060 (Two-hybrid), ZNF398 (Affinity Capture-MS), ZNF398 (Two-hybrid), ZNF282 (Affinity Capture-MS), ZNF398 (Affinity Capture-MS), ZNF398 (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: A0A163UT06, A2AGX3, A6QPM3, B1AUS7, E9Q3T6, O60224, O75626, P0C6Y7, P52736, Q13029, Q16384, Q16385, Q3UZD5, Q5R5M1, Q60636, Q63755, Q6P2A1, Q6PGE4, Q7RTT6, Q80V63, Q86UQ0, Q8BZ97, Q8TD17, Q96EQ9, Q99909, Q9GZV8, Q9NQV5, Q9NQV7, Q9NQV8, Q9NQW5, Q9NQX0, Q9QZP2, Q9UDV7, Q9UKN5, Q9ULD5, A2A761, A6NFI3, A6NK75, A6NM28, A6NP11

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1057 predictions. Top by Δscore:

Variant	Effect	Δscore
7:149153944:GAC:G	acceptor_gain	1.0000
7:149154326:G:GT	donor_gain	1.0000
7:149166283:GG:G	donor_gain	1.0000
7:149166284:GG:G	donor_gain	1.0000
7:149166290:GC:G	donor_gain	1.0000
7:149166291:C:G	donor_gain	1.0000
7:149166312:G:GT	donor_gain	1.0000
7:149166812:CCTAG:C	acceptor_loss	1.0000
7:149166816:G:GT	acceptor_loss	1.0000
7:149166816:GATT:G	acceptor_gain	1.0000
7:149166927:GAAG:G	donor_gain	1.0000
7:149166930:GGTA:G	donor_loss	1.0000
7:149166931:G:C	donor_loss	1.0000
7:149166931:G:GG	donor_gain	1.0000
7:149176459:A:AG	acceptor_gain	1.0000
7:149176460:C:G	acceptor_gain	1.0000
7:149176461:A:AG	acceptor_gain	1.0000
7:149176462:A:G	acceptor_gain	1.0000
7:149176578:GCTG:G	donor_gain	1.0000
7:149176579:CTGGT:C	donor_loss	1.0000
7:149176580:TG:T	donor_gain	1.0000
7:149176580:TGG:T	donor_loss	1.0000
7:149176581:GG:G	donor_gain	1.0000
7:149176581:GGTG:G	donor_loss	1.0000
7:149176582:G:A	donor_loss	1.0000
7:149176582:G:GG	donor_gain	1.0000
7:149176583:TGAG:T	donor_loss	1.0000
7:149176584:G:GT	donor_loss	1.0000
7:149147591:GCCGC:G	donor_gain	0.9900
7:149153927:T:G	acceptor_gain	0.9900

AlphaMissense

4216 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:149179430:T:C	F520L	1.000
7:149179431:T:C	F520S	1.000
7:149179432:C:A	F520L	1.000
7:149179432:C:G	F520L	1.000
7:149179457:C:G	H529D	1.000
7:149179514:T:C	F548L	1.000
7:149179515:T:C	F548S	1.000
7:149179516:C:A	F548L	1.000
7:149179516:C:G	F548L	1.000
7:149179533:T:C	L554P	1.000
7:149179598:T:C	F576L	1.000
7:149179600:C:A	F576L	1.000
7:149179600:C:G	F576L	1.000
7:149179157:T:C	C429R	0.999
7:149179178:T:C	F436L	0.999
7:149179179:T:C	F436S	0.999
7:149179180:T:A	F436L	0.999
7:149179180:T:G	F436L	0.999
7:149179205:C:G	H445D	0.999
7:149179262:T:C	F464L	0.999
7:149179264:C:A	F464L	0.999
7:149179264:C:G	F464L	0.999
7:149179289:C:G	H473D	0.999
7:149179325:T:C	C485R	0.999
7:149179334:T:A	C488S	0.999
7:149179335:G:C	C488S	0.999
7:149179346:T:C	F492L	0.999
7:149179347:T:C	F492S	0.999
7:149179348:C:A	F492L	0.999
7:149179348:C:G	F492L	0.999

dbSNP variants (sampled 300 via entrez): RS1000032075 (7:149157004 C>G), RS1000048169 (7:149165035 A>C,G), RS1000049038 (7:149125009 A>C), RS1000103072 (7:149164699 G>A), RS1000160732 (7:149151358 G>A,T), RS1000232128 (7:149159577 G>A,T), RS1000236509 (7:149151090 G>A), RS1000316359 (7:149130561 T>G), RS1000362548 (7:149145138 T>A), RS1000398837 (7:149125310 G>A), RS1000408586 (7:149157250 C>A,T), RS1000481840 (7:149136691 C>G,T), RS1000608861 (7:149169360 C>T), RS1000647061 (7:149146902 A>G), RS1000656636 (7:149129127 A>G)

Disease associations

OMIM: gene MIM:618593 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004600_38	Eosinophil percentage of white cells	7.000000e-41
GCST004606_149	Eosinophil count	2.000000e-32
GCST004617_14	Eosinophil percentage of granulocytes	1.000000e-40
GCST004623_113	Neutrophil percentage of granulocytes	1.000000e-38
GCST004624_107	Sum eosinophil basophil counts	2.000000e-28
GCST90002399_187	Neutrophil percentage of white cells	6.000000e-16

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
sodium arsenite	increases expression, increases abundance	2
Benzo(a)pyrene	affects methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Leflunomide	increases expression	1
Arsenic	increases abundance, increases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8YF	Ubigene HCT 116 ZNF398 KO	Cancer cell line	Male
CVCL_XW41	HEK293 eGFP-ZNF398	Transformed cell line	Female

Clinical trials (associated diseases)

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