ZNF397

Summary

ZNF397 (zinc finger protein 397, HGNC:18818) is a protein-coding gene on chromosome 18q12.2, encoding Zinc finger protein 397 (Q8NF99). Isoform 3 acts as a DNA-dependent transcriptional repressor.

This gene encodes a protein with a N-terminal SCAN domain, and the longer isoform contains nine C2H2-type zinc finger repeats in the C-terminal domain. The protein localizes to centromeres during interphase and early prophase, and different isoforms can repress or activate transcription in transfection studies. Multiple transcript variants encoding different isoforms have been found for this gene. Additional variants have been described, but their biological validity has not been determined.

Source: NCBI Gene 84307 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_001135178

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18818
Approved symbol	ZNF397
Name	zinc finger protein 397
Location	18q12.2
Locus type	gene with protein product
Status	Approved
Aliases	ZSCAN15, MGC13250
Ensembl gene	ENSG00000186812
Ensembl biotype	protein_coding
OMIM	609601
Entrez	84307

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000261333, ENST00000330501, ENST00000355632, ENST00000585800, ENST00000588119, ENST00000589420, ENST00000589630, ENST00000590470, ENST00000591206, ENST00000591505, ENST00000592264, ENST00000601719, ENST00000892487, ENST00000892488, ENST00000892489, ENST00000892490, ENST00000892491, ENST00000912773, ENST00000957143

RefSeq mRNA: 2 — MANE Select: NM_001135178 NM_001135178, NM_032347

CCDS: CCDS32814, CCDS45852

Canonical transcript exons

ENST00000330501 — 4 exons

Exon	Start	End
ENSE00000797049	35242391	35242884
ENSE00001606963	35245262	35249808
ENSE00003460384	35243152	35243293
ENSE00003841953	35241034	35241109

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.2350 / max 301.4259, expressed in 1756 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169930	12.4887	1716
169931	1.7463	1058

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.19	gold quality
corpus callosum	UBERON:0002336	94.01	gold quality
oocyte	CL:0000023	92.50	gold quality
calcaneal tendon	UBERON:0003701	92.34	gold quality
ganglionic eminence	UBERON:0004023	92.33	gold quality
embryo	UBERON:0000922	92.32	gold quality
colonic epithelium	UBERON:0000397	92.17	gold quality
cortical plate	UBERON:0005343	91.18	gold quality
pancreatic ductal cell	CL:0002079	90.78	gold quality
ventricular zone	UBERON:0003053	89.95	gold quality
kidney epithelium	UBERON:0004819	89.09	gold quality
inferior vagus X ganglion	UBERON:0005363	88.64	gold quality
tendon	UBERON:0000043	88.06	gold quality
ileal mucosa	UBERON:0000331	87.81	gold quality
vermiform appendix	UBERON:0001154	87.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.56	gold quality
primary visual cortex	UBERON:0002436	87.41	gold quality
left ovary	UBERON:0002119	87.36	gold quality
right ovary	UBERON:0002118	87.17	gold quality
rectum	UBERON:0001052	87.14	gold quality
sural nerve	UBERON:0015488	87.09	gold quality
endocervix	UBERON:0000458	86.97	gold quality
tonsil	UBERON:0002372	86.92	gold quality
body of uterus	UBERON:0009853	86.91	gold quality
tibial nerve	UBERON:0001323	86.88	gold quality
cerebellar hemisphere	UBERON:0002245	86.86	gold quality
cerebellar cortex	UBERON:0002129	86.84	gold quality
spinal cord	UBERON:0002240	86.83	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.82	gold quality
islet of Langerhans	UBERON:0000006	86.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.58
E-MTAB-7606	no	297.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting ZNF397, 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-4534	99.99	66.58	1907
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-8086	97.21	64.13	331
HSA-MIR-6872-3P	97.08	66.99	750
HSA-MIR-3184-3P	96.96	66.91	845
HSA-MIR-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888
HSA-MIR-1915-5P	95.25	65.78	571
HSA-MIR-5009-5P	94.82	63.89	775
HSA-MIR-6741-5P	93.86	63.06	437
HSA-MIR-6720-3P	91.34	60.49	67

Literature-anchored findings (GeneRIF, showing 1)

• ZNF397, a new class of interphase to early prophase-specific, SCAN-zinc-finger, mammalian centromere protein. (PMID:18369653)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp397	ENSMUSG00000024276
rattus_norvegicus	Zfp397	ENSRNOG00000048101

Paralogs (30): ZNF263 (ENSG00000006194), ZNF213 (ENSG00000085644), ZNF500 (ENSG00000103199), ZKSCAN1 (ENSG00000106261), ZNF205 (ENSG00000122386), ZSCAN9 (ENSG00000137185), PGBD1 (ENSG00000137338), ZNF215 (ENSG00000149054), ZSCAN12 (ENSG00000158691), ZNF394 (ENSG00000160908), ZNF75A (ENSG00000162086), ZSCAN21 (ENSG00000166529), ZNF232 (ENSG00000167840), ZNF24 (ENSG00000172466), ZNF449 (ENSG00000173275), ZSCAN4 (ENSG00000180532), ZSCAN22 (ENSG00000182318), ZNF75D (ENSG00000186376), ZNF396 (ENSG00000186496), ZSCAN30 (ENSG00000186814), ZKSCAN4 (ENSG00000187626), ZSCAN23 (ENSG00000187987), ZKSCAN3 (ENSG00000189298), ZSCAN16 (ENSG00000196812), ZSCAN25 (ENSG00000197037), ZSCAN26 (ENSG00000197062), ZNF165 (ENSG00000197279), ZKSCAN8 (ENSG00000198315), ZSCAN31 (ENSG00000235109), ZNF853 (ENSG00000236609)

Protein

Protein identifiers

Zinc finger protein 397 — Q8NF99 (reviewed: Q8NF99)

Alternative names: Zinc finger and SCAN domain-containing protein 15, Zinc finger protein 47

All UniProt accessions (5): Q8NF99, K7EIM5, K7ERU5, M0R288, Q96K65

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 3 acts as a DNA-dependent transcriptional repressor.

Subunit / interactions. Isoforms 1 and 3 can both homo- and hetero-associate. Homo-association of isoform 1 is dependent on the presence of the SCAN domain.

Subcellular location. Nucleus Nucleus. Cytoplasm.

Tissue specificity. Expressed strongly in testis, moderately in skeletal muscle, pancreas and prostate, and weakly in heart, placenta, liver, kidney, spleen, thymus and small intestine.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NF99-1	1, ZNF397-fu	yes
Q8NF99-2	2
Q8NF99-3	3, Truncated, ZNF397-nf

RefSeq proteins (2): NP_001128650, NP_115723 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003309	SCAN_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR038269	SCAN_sf	Homologous_superfamily
IPR050758	Znf_C2H2-type	Family

Pfam: PF00096, PF02023

UniProt features (22 total): zinc finger region 9, cross-link 4, splice variant 4, chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NF99-F1	68.39	0.34

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 (5): 31, 55, 171, 202, 251

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 83 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, chr18q12, BASAKI_YBX1_TARGETS_DN, GOCC_NUCLEOLUS, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY, HAMAI_APOPTOSIS_VIA_TRAIL_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MARTENS_TRETINOIN_RESPONSE_DN, LEE_DIFFERENTIATING_T_LYMPHOCYTE, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GSE5503_MLN_DC_VS_PLN_DC_ACTIVATED_ALLOGENIC_TCELL_DN

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (8): 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), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
protein dimerization activity	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic 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
identical protein binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cytoskeleton	1

Protein interactions and networks

STRING

578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF397	RMP24	Q32NC0	479
ZNF397	C14orf119	Q9NWQ9	417
ZNF397	IFTAP	Q86VG3	375
ZNF397	RNF214	Q8ND24	369
ZNF397	SPACA9	Q96E40	369
ZNF397	PRPSAP2	O60256	333
ZNF397	GRIK2	Q13002	330
ZNF397	CCDC178	Q5BJE1	327
ZNF397	PRSS37	A4D1T9	321
ZNF397	LRFN1	Q9P244	313
ZNF397	RNF25	Q96BH1	306
ZNF397	GAREM1	Q9H706	298
ZNF397	LNPK	Q9C0E8	295
ZNF397	TNRC18	O15417	284
ZNF397	DUSP29	Q68J44	283

IntAct

53 interactions, top by confidence:

A	B	Type	Score
ZNF446	ZNF397	psi-mi:“MI:0915”(physical association)	0.850
SCAND1	ZNF397	psi-mi:“MI:0915”(physical association)	0.740
ZNF397	ZNF24	psi-mi:“MI:0914”(association)	0.640
ZNF397	ZNF213	psi-mi:“MI:0914”(association)	0.640
PRKAA2	ZNF397	psi-mi:“MI:0915”(physical association)	0.560
LMO4	ZNF397	psi-mi:“MI:0915”(physical association)	0.560
ZNF410	ZNF397	psi-mi:“MI:0915”(physical association)	0.560
ZNF397	ZNF446	psi-mi:“MI:0915”(physical association)	0.560
ZNF446	ZNF397	psi-mi:“MI:0915”(physical association)	0.560
ZNF397	PRKAA2	psi-mi:“MI:0915”(physical association)	0.560
ZNF397	LMO4	psi-mi:“MI:0915”(physical association)	0.560
ZSCAN32	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZNF397	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZNF483	ZNF197	psi-mi:“MI:0914”(association)	0.530
SLC9A8	ZNF432	psi-mi:“MI:0914”(association)	0.530
ZNF263	AHCYL1	psi-mi:“MI:0914”(association)	0.530
ZNF263	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
RGS3	ZNF646	psi-mi:“MI:0914”(association)	0.350

BioGRID (128): ZNF397 (Two-hybrid), ZNF397 (Two-hybrid), ZNF397 (Two-hybrid), ZNF397 (Two-hybrid), ZNF397 (Affinity Capture-MS), STK40 (Affinity Capture-MS), ZKSCAN3 (Affinity Capture-MS), ZKSCAN1 (Affinity Capture-MS), ZNF24 (Affinity Capture-MS), ZKSCAN8 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZNF232 (Affinity Capture-MS), ZSCAN21 (Affinity Capture-MS), P3H1 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS)

ESM2 similar proteins: A1YEP8, A1YEV9, A1YFW2, A1YG26, A1YG48, A1YG60, A2T6E3, A2T6V8, A2T712, A2T736, A2T7D2, A2T7F4, A2T7L7, A2T812, A6QNZ0, O14709, O15535, O43296, O43309, P10073, P17023, P17097, P49910, Q07231, Q12901, Q15776, Q16670, Q1LZ87, Q3MJ62, Q53GI3, Q571J5, Q5JNZ3, Q5RAE6, Q5RBX0, Q5RCD9, Q5RJ54, Q7Z7L9, Q86W11, Q8IZ26, Q8NF99

Diamond homologs: A1YEP8, A1YEQ3, A1YEV9, A1YFW2, A1YFW6, A1YG26, A1YG48, A1YG60, A1YGJ4, A1YGK6, A2T6E3, A2T6V8, A2T6W2, A2T712, A2T736, A2T7D2, A2T7D7, A2T7F2, A2T7F4, A2T7L7, A2T812, A6QNZ0, A6QPT6, B2KFW1, O14709, O14771, O14978, O15535, O43309, O60304, O95125, P10073, P17022, P17028, P17029, P17040, P28698, P49910, P51815, P59923

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1645 predictions. Top by Δscore:

Variant	Effect	Δscore
18:35242828:G:GT	donor_gain	1.0000
18:35242860:G:GT	donor_gain	1.0000
18:35245346:G:GT	donor_gain	1.0000
18:35245352:G:GG	donor_gain	1.0000
18:35245385:G:GT	donor_gain	1.0000
18:35245398:G:T	donor_gain	1.0000
18:35263942:TA:T	donor_loss	1.0000
18:35263944:C:A	donor_loss	1.0000
18:35264451:CGCTC:C	acceptor_gain	1.0000
18:35241116:G:T	donor_gain	0.9900
18:35241288:G:GT	donor_gain	0.9900
18:35241289:A:T	donor_gain	0.9900
18:35241314:ACTTC:A	donor_gain	0.9900
18:35242389:A:AG	acceptor_gain	0.9900
18:35242390:G:GG	acceptor_gain	0.9900
18:35242541:TGA:T	donor_gain	0.9900
18:35242849:G:GT	donor_gain	0.9900
18:35242953:G:GG	donor_gain	0.9900
18:35243291:GTG:G	donor_gain	0.9900
18:35245319:G:T	donor_gain	0.9900
18:35245347:A:T	donor_gain	0.9900
18:35245385:G:T	donor_gain	0.9900
18:35245467:A:T	donor_gain	0.9900
18:35254379:CAT:C	acceptor_gain	0.9900
18:35254382:C:CC	acceptor_gain	0.9900
18:35263943:A:AC	donor_gain	0.9900
18:35263944:C:CC	donor_gain	0.9900
18:35264453:CTC:C	acceptor_gain	0.9900
18:35264453:CTCCT:C	acceptor_loss	0.9900
18:35264454:TC:T	acceptor_gain	0.9900

AlphaMissense

3547 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:35245669:T:C	F322L	0.999
18:35245671:T:A	F322L	0.999
18:35245671:T:G	F322L	0.999
18:35245753:T:C	F350L	0.999
18:35245755:C:A	F350L	0.999
18:35245755:C:G	F350L	0.999
18:35245837:T:C	F378L	0.999
18:35245839:C:A	F378L	0.999
18:35245839:C:G	F378L	0.999
18:35245921:T:C	F406L	0.999
18:35245923:T:A	F406L	0.999
18:35245923:T:G	F406L	0.999
18:35246005:T:C	F434L	0.999
18:35246007:C:A	F434L	0.999
18:35246007:C:G	F434L	0.999
18:35246024:T:C	L440P	0.999
18:35246089:T:C	F462L	0.999
18:35246091:C:A	F462L	0.999
18:35246091:C:G	F462L	0.999
18:35246108:T:C	L468P	0.999
18:35245940:T:C	L412P	0.998
18:35245950:T:A	H415Q	0.998
18:35245950:T:G	H415Q	0.998
18:35246032:C:G	H443D	0.998
18:35246034:T:A	H443Q	0.998
18:35246034:T:G	H443Q	0.998
18:35246116:C:G	H471D	0.998
18:35246118:T:A	H471Q	0.998
18:35246118:T:G	H471Q	0.998
18:35245856:T:C	L384P	0.997

dbSNP variants (sampled 300 via entrez): RS1000012686 (18:35245560 T>C), RS1000014415 (18:35251455 CAAAG>C), RS1000247201 (18:35242403 T>C), RS1000662403 (18:35241278 C>T), RS1000663655 (18:35255443 G>A), RS1000782119 (18:35248906 T>A,C), RS1001234507 (18:35259216 T>C), RS1001297989 (18:35252047 A>G), RS1001329148 (18:35252294 T>C), RS1001374287 (18:35248631 A>C,G), RS1001508722 (18:35248404 C>T), RS1001658543 (18:35254539 G>C,T), RS1001760760 (18:35242321 C>T), RS1001991802 (18:35241405 A>G), RS1002022816 (18:35254277 G>A)

Disease associations

OMIM: gene MIM:609601 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006108_2	Facial morphology	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004743	facial morphology

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
butylparaben	increases 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
belinostat	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Potassium Chloride	decreases expression, decreases response to substance	1
Smoke	decreases expression	1
Dronabinol	decreases expression, decreases response to substance	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Copper Sulfate	decreases expression	1
Magnetite Nanoparticles	decreases expression	1

Clinical trials (associated diseases)

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