ZNF396

Summary

ZNF396 (zinc finger protein 396, HGNC:18824) is a protein-coding gene on chromosome 18q12.2, encoding Zinc finger protein 396 (Q96N95). Isoform 1 and isoform 2 act as DNA-dependent transcriptional repressors.

Enables protein heterodimerization activity; protein homodimerization activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of DNA-templated transcription. Located in cytoplasm and nucleus.

Source: NCBI Gene 252884 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001322286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18824
Approved symbol	ZNF396
Name	zinc finger protein 396
Location	18q12.2
Locus type	gene with protein product
Status	Approved
Aliases	ZSCAN14, FLJ31213
Ensembl gene	ENSG00000186496
Ensembl biotype	protein_coding
OMIM	609600
Entrez	252884

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000306346, ENST00000585522, ENST00000586585, ENST00000586687, ENST00000587422, ENST00000589332, ENST00000862521, ENST00000862522, ENST00000862523, ENST00000931984, ENST00000931985, ENST00000945089

RefSeq mRNA: 4 — MANE Select: NM_001322286 NM_001322286, NM_001322290, NM_001322291, NM_145756

CCDS: CCDS11913, CCDS82246, CCDS82247

Canonical transcript exons

ENST00000589332 — 4 exons

Exon	Start	End
ENSE00001134290	35373456	35373600
ENSE00001197905	35377278	35377337
ENSE00001327939	35373876	35374364
ENSE00002891752	35366694	35369660

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 89.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.8661 / max 41.2566, expressed in 956 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171646	1.8661	956

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	89.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.25	gold quality
bronchial epithelial cell	CL:0002328	79.11	gold quality
bronchus	UBERON:0002185	78.24	gold quality
oviduct epithelium	UBERON:0004804	75.26	gold quality
right uterine tube	UBERON:0001302	74.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.09	gold quality
sperm	CL:0000019	73.83	silver quality
islet of Langerhans	UBERON:0000006	72.76	gold quality
calcaneal tendon	UBERON:0003701	71.25	gold quality
left lobe of thyroid gland	UBERON:0001120	71.23	gold quality
thyroid gland	UBERON:0002046	70.96	gold quality
right lobe of thyroid gland	UBERON:0001119	70.65	gold quality
fallopian tube	UBERON:0003889	69.98	gold quality
pancreas	UBERON:0001264	69.28	gold quality
descending thoracic aorta	UBERON:0002345	68.97	gold quality
right testis	UBERON:0004534	68.42	gold quality
right adrenal gland	UBERON:0001233	68.28	gold quality
minor salivary gland	UBERON:0001830	68.28	gold quality
body of pancreas	UBERON:0001150	68.23	gold quality
left testis	UBERON:0004533	68.23	gold quality
right adrenal gland cortex	UBERON:0035827	68.15	gold quality
testis	UBERON:0000473	68.04	gold quality
left adrenal gland	UBERON:0001234	67.95	gold quality
ventricular zone	UBERON:0003053	67.71	gold quality
cortical plate	UBERON:0005343	67.59	gold quality
adenohypophysis	UBERON:0002196	67.45	gold quality
gall bladder	UBERON:0002110	67.35	gold quality
saliva-secreting gland	UBERON:0001044	67.19	gold quality
left adrenal gland cortex	UBERON:0035825	66.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting ZNF396, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-518A-5P	99.70	69.01	2209

Literature-anchored findings (GeneRIF, showing 1)

• ZNF396 might repress Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous differentiation in basal cell carcinoma. (PMID:24445935)

Cross-species orthologs

0 orthologs

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), ZNF397 (ENSG00000186812), 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 396 — Q96N95 (reviewed: Q96N95)

Alternative names: Zinc finger and SCAN domain-containing protein 14

All UniProt accessions (3): Q96N95, K7EK38, K7ERR8

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 1 and isoform 2 act as DNA-dependent transcriptional repressors.

Subunit / interactions. Isoforms 1 and 2 can both homo- and hetero-associate.

Subcellular location. Nucleus Nucleus. Cytoplasm.

Tissue specificity. Expressed strongly in liver, moderately in skeletal muscle and weakly in kidney, pancreas, spleen and prostate.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q96N95-1	1, ZNF396-fu	yes
Q96N95-2	2, Truncated, ZNF396-nf
Q96N95-3	3

RefSeq proteins (4): NP_001309215, NP_001309219, NP_001309220, NP_665699 (=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
IPR050916	SCAN-C2H2_zinc_finger	Family

Pfam: PF00096, PF02023

UniProt features (10 total): zinc finger region 3, splice variant 3, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N95-F1	57.72	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): chr18q12, TGGAAA_NFAT_Q4_01, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, PEDRIOLI_MIR31_TARGETS_DN, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, DACH1_TARGET_GENES, DIDO1_TARGET_GENES, FOXN3_TARGET_GENES, NCOA6_TARGET_GENES

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

GO Molecular Function (10): 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), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737)

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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF396	RHOBTB3	O94955	531
ZNF396	CFAP20DC	Q6ZVT6	506
ZNF396	RMP24	Q32NC0	506
ZNF396	PLEKHN1	Q494U1	480
ZNF396	TRIM77	I1YAP6	473
ZNF396	PTPDC1	A2A3K4	446
ZNF396	IQCC	Q4KMZ1	445
ZNF396	CORO1C	Q9ULV4	438
ZNF396	GPR19	Q15760	433
ZNF396	SCIN	Q9Y6U3	427
ZNF396	MCCC1	Q96RQ3	424
ZNF396	TMEM212	A6NML5	420
ZNF396	NAA11	Q9BSU3	418
ZNF396	DPH6	Q7L8W6	417
ZNF396	SVOPL	Q8N434	409

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ZNF396	ZNF24	psi-mi:“MI:0914”(association)	0.530
ZNF396	BCL7B	psi-mi:“MI:0915”(physical association)	0.400
NFE2L2	ZNF396	psi-mi:“MI:0915”(physical association)	0.370
ZNF396	ZSCAN1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (51): ZNF396 (Two-hybrid), ZNF396 (Two-hybrid), ZNF396 (Two-hybrid), ZKSCAN3 (Affinity Capture-MS), ZKSCAN4 (Affinity Capture-MS), ZNF24 (Affinity Capture-MS), PGBD1 (Affinity Capture-MS), ZKSCAN8 (Affinity Capture-MS), ZBED9 (Affinity Capture-MS), ZNF174 (Affinity Capture-MS), ZNF446 (Affinity Capture-MS), ZNF445 (Affinity Capture-MS), ZSCAN20 (Affinity Capture-MS), ZSCAN18 (Affinity Capture-MS), SCAND1 (Affinity Capture-MS)

ESM2 similar proteins: A1YEQ3, A1YEV9, A1YFW6, A1YG26, A1YG48, A1YG60, A2T6W2, A2T712, A2T736, A2T7L7, A6QNZ0, O14978, O15535, O95125, P17022, P17029, P49910, P51815, P59923, Q07231, Q15776, Q16670, Q1LZ87, Q3MJ62, Q3URR7, Q4KLI1, Q4R8H9, Q53GI3, Q5R670, Q5R741, Q5RJ54, Q63HK3, Q642B9, Q6P9G9, Q810A1, Q86W11, Q8BGS3, Q8CF60, Q8NF99, Q92670

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

671 predictions. Top by Δscore:

Variant	Effect	Δscore
18:35369661:C:CC	acceptor_gain	1.0000
18:35373491:C:CA	donor_gain	1.0000
18:35373875:CCTG:C	donor_gain	1.0000
18:35374360:CACTC:C	acceptor_gain	1.0000
18:35374388:G:GC	acceptor_gain	1.0000
18:35369658:CAT:C	acceptor_gain	0.9900
18:35369659:ATC:A	acceptor_loss	0.9900
18:35369660:TCT:T	acceptor_loss	0.9900
18:35369661:CTGA:C	acceptor_loss	0.9900
18:35369662:T:G	acceptor_loss	0.9900
18:35373480:C:CA	donor_gain	0.9900
18:35373870:TCTTA:T	donor_loss	0.9900
18:35373871:CTTA:C	donor_loss	0.9900
18:35373872:TTAC:T	donor_loss	0.9900
18:35373873:TA:T	donor_loss	0.9900
18:35374362:CTC:C	acceptor_gain	0.9900
18:35374364:CCT:C	acceptor_gain	0.9900
18:35374365:C:CC	acceptor_gain	0.9900
18:35374365:CTT:C	acceptor_loss	0.9900
18:35374366:T:C	acceptor_gain	0.9900
18:35374366:T:TC	acceptor_gain	0.9900
18:35374370:A:AC	acceptor_gain	0.9900
18:35374370:A:C	acceptor_gain	0.9900
18:35374372:A:AC	acceptor_gain	0.9900
18:35374372:A:C	acceptor_gain	0.9900
18:35374376:T:C	acceptor_gain	0.9900
18:35374376:T:TC	acceptor_gain	0.9900
18:35374385:C:CT	acceptor_gain	0.9900
18:35374386:A:T	acceptor_gain	0.9900
18:35374388:G:C	acceptor_gain	0.9900

AlphaMissense

2215 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:35369275:A:C	F316L	0.998
18:35369275:A:T	F316L	0.998
18:35369277:A:G	F316L	0.998
18:35369359:G:C	F288L	0.998
18:35369359:G:T	F288L	0.998
18:35369361:A:G	F288L	0.998
18:35369443:A:C	F260L	0.994
18:35369443:A:T	F260L	0.994
18:35369445:A:G	F260L	0.994
18:35369327:C:G	R299P	0.993
18:35369360:A:G	F288S	0.991
18:35369332:A:C	H297Q	0.989
18:35369332:A:T	H297Q	0.989
18:35369334:G:C	H297D	0.989
18:35369276:A:G	F316S	0.988
18:35369320:A:C	H301Q	0.987
18:35369320:A:T	H301Q	0.987
18:35369418:G:C	H269D	0.986
18:35369298:A:G	C309R	0.985
18:35369330:C:G	R298P	0.985
18:35369342:A:G	L294P	0.985
18:35374075:A:G	L73P	0.983
18:35369258:A:G	L322P	0.982
18:35374128:G:C	F55L	0.982
18:35374128:G:T	F55L	0.982
18:35374130:A:G	F55L	0.982
18:35369354:C:G	R290P	0.981
18:35369360:A:C	F288C	0.981
18:35373993:G:C	F100L	0.981
18:35373993:G:T	F100L	0.981

dbSNP variants (sampled 300 via entrez): RS1000070577 (18:35367063 T>G), RS1000126258 (18:35375330 G>A,T), RS1000421987 (18:35367374 G>A), RS1001014216 (18:35369056 A>C,T), RS1001119409 (18:35376866 A>T), RS1002067734 (18:35370310 A>G), RS1002175836 (18:35377709 G>A), RS1002180142 (18:35370651 T>C), RS1002416968 (18:35370659 C>G), RS1002696512 (18:35377468 T>A), RS1003186692 (18:35369235 T>C), RS1003294157 (18:35376477 G>A,T), RS1003368695 (18:35374743 C>T), RS1003734674 (18:35376183 C>A), RS1003921608 (18:35366427 T>C,G)

Disease associations

OMIM: gene MIM:609600 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002282_10	Parasitemia in Tripanosoma cruzi seropositivity	6.000000e-07
GCST003059_21	Parkinson’s disease	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005528	parasitemia measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Nickel	decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases methylation	1
ferrous chloride	decreases expression	1
pentabromodiphenyl ether	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Glyphosate	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Potassium Chloride	decreases expression, decreases response to substance	1
Smoke	decreases expression	1
Dronabinol	decreases expression, decreases response to substance	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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