ZNF93

Summary

ZNF93 (zinc finger protein 93, HGNC:13169) is a protein-coding gene on chromosome 19p12, encoding Zinc finger protein 93 (P35789). Transcription factor specifically required to repress long interspersed nuclear element 1 (L1) retrotransposons: recognizes and binds L1 sequences and repress their expression by recruiting a repressive complex containing TRIM28/KAP1.

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific. Involved in transposable element silencing. Predicted to be located in nucleoplasm. Predicted to be active in nucleus.

Source: NCBI Gene 81931 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 110 total
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_031218

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13169
Approved symbol	ZNF93
Name	zinc finger protein 93
Location	19p12
Locus type	gene with protein product
Status	Approved
Aliases	HPF34, TF34, FLJ12488
Ensembl gene	ENSG00000184635
Ensembl biotype	protein_coding
OMIM	603975
Entrez	81931

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000343769, ENST00000586021, ENST00000588146, ENST00000589903, ENST00000591366, ENST00000592160, ENST00000592245, ENST00000592613

RefSeq mRNA: 1 — MANE Select: NM_031218 NM_031218

CCDS: CCDS32973

Canonical transcript exons

ENST00000343769 — 4 exons

Exon	Start	End
ENSE00001375338	19933182	19935575
ENSE00003543263	19916560	19916655
ENSE00003686507	19900946	19901091
ENSE00003694366	19915280	19915406

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 95.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.2832 / max 520.5188, expressed in 1562 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174838	5.6181	1398
174839	2.6464	805
174837	0.6396	360
174836	0.3791	181

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.52	gold quality
buccal mucosa cell	CL:0002336	94.90	gold quality
oocyte	CL:0000023	92.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.63	gold quality
diaphragm	UBERON:0001103	87.42	gold quality
embryo	UBERON:0000922	86.89	gold quality
ganglionic eminence	UBERON:0004023	86.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.73	gold quality
ventricular zone	UBERON:0003053	83.12	gold quality
cortical plate	UBERON:0005343	81.90	gold quality
left ventricle myocardium	UBERON:0006566	81.53	gold quality
mucosa of urinary bladder	UBERON:0001259	80.42	silver quality
thyroid gland	UBERON:0002046	79.69	gold quality
bone marrow	UBERON:0002371	79.52	gold quality
right lobe of thyroid gland	UBERON:0001119	79.38	gold quality
nasal cavity epithelium	UBERON:0005384	79.38	silver quality
endometrium	UBERON:0001295	79.17	gold quality
left lobe of thyroid gland	UBERON:0001120	78.96	gold quality
hair follicle	UBERON:0002073	78.81	gold quality
superficial temporal artery	UBERON:0001614	78.80	silver quality
mammary duct	UBERON:0001765	78.63	silver quality
epithelium of mammary gland	UBERON:0003244	78.03	silver quality
islet of Langerhans	UBERON:0000006	78.02	gold quality
ileal mucosa	UBERON:0000331	77.85	gold quality
cerebellar vermis	UBERON:0004720	77.85	gold quality
vastus lateralis	UBERON:0001379	77.68	gold quality
thymus	UBERON:0002370	77.18	silver quality
upper arm skin	UBERON:0004263	77.12	gold quality
adrenal tissue	UBERON:0018303	76.92	gold quality
oviduct epithelium	UBERON:0004804	76.14	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	187.22
E-ANND-3	no	5.25

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1721.1	ZNF93	More than 3 adjacent zinc fingers
MA1721.2	ZNF93	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:25274305

miRNA regulators (miRDB)

48 targeting ZNF93, 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-3064-3P	100.00	70.09	1254
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-1911-5P	98.92	67.53	325
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-3945	98.68	64.21	553
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-3691-5P	98.62	65.88	552

Literature-anchored findings (GeneRIF, showing 1)

• zinc finger proteins, and ZNF93 in particular, are involved in resistance to ET-743 and PM00104 (PMID:19742314)

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger protein 93 — P35789 (reviewed: P35789)

Alternative names: Zinc finger protein 505, Zinc finger protein HTF34

All UniProt accessions (5): P35789, K7EPG7, K7EPV7, K7EQ36, K7ES58

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor specifically required to repress long interspersed nuclear element 1 (L1) retrotransposons: recognizes and binds L1 sequences and repress their expression by recruiting a repressive complex containing TRIM28/KAP1. Not able to repress expression of all subtypes of L1 elements. Binds to the 5’ end of L1PA4, L1PA5 and L1PA6 subtypes, and some L1PA3 subtypes. Does not bind to L1PA7 or older subtypes nor at the most recently evolved L1PA2 and L1Hs. 50% of L1PA3 elements have lost the ZNF93-binding site, explaining why ZNF93 is not able to repress their expression.

Subcellular location. Nucleus.

Miscellaneous. ZNF93 is only present in primates and evolved to repress the primate L1 lineage until 12.5 million years. Evolution stopped when the L1PA3-subfamily of retrotransposons, that escape repression by ZNF93 through the removal of the ZNF93-binding site, appeared. Confers resistance to ET-743 (trabectedin, Yondelis) and PM00104 (Zalypsis), 2 marine derived compounds with antitumor activity in cancer cell lines.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P35789-1	1	yes
P35789-2	2
P35789-3	3

RefSeq proteins (1): NP_112495* (*=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, PF13465

UniProt features (32 total): zinc finger region 17, sequence conflict 7, helix 3, splice variant 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7Z36	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35789-F1	75.28	0.18

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 78 (showing top): WANG_CLIM2_TARGETS_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MODULE_205, DOANE_RESPONSE_TO_ANDROGEN_DN, SAMOLS_TARGETS_OF_KHSV_MIRNAS_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, chr19p12, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_DN, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_UP, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_TRANSPOSITION

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), transposable element silencing (GO:0010526), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
negative regulation of gene expression	1
retrotransposition	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	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
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF93	TRIM28	Q13263	483
ZNF93	OR6S1	Q8NH40	448
ZNF93	XRCC1	P18887	423
ZNF93	SETDB1	Q15047	403
ZNF93	SLC66A1LP	A1A4F0	398
ZNF93	PDHX	O00330	382
ZNF93	GLRB	P48167	321
ZNF93	EID2B	Q96D98	311
ZNF93	XTBD1	Q96HQ2	300
ZNF93	TDRD1	Q9BXT4	279
ZNF93	MOV10	Q9HCE1	274
ZNF93	VSTM2B	A6NLU5	269
ZNF93	MOV10L1	Q9BXT6	268
ZNF93	PRKRIP1	Q9H875	249
ZNF93	ACKR5	O15218	248

IntAct

4 interactions, top by confidence:

A	B	Type	Score
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350
ZNF93	H1-4	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): ZNF93 (Affinity Capture-MS), ZNF93 (Affinity Capture-MS), ZNF93 (Affinity Capture-MS), ZNF93 (Reconstituted Complex), ZNF93 (Affinity Capture-MS), ZNF93 (Affinity Capture-MS), TRIM28 (Reconstituted Complex), ZNF93 (Affinity Capture-MS), ZNF93 (Affinity Capture-MS), ZNF93 (Affinity Capture-RNA)

ESM2 similar proteins: A2VDQ7, A6NNF4, A8MQ14, A8MTY0, E9QAG8, O75290, O75373, P08043, P0CJ79, P10751, P17017, P17027, P17039, P35789, P51522, P51523, Q08AN1, Q14585, Q14587, Q3SYV7, Q3ZCX4, Q4R4C7, Q52M93, Q5MCW4, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6ECI4, Q6JLC9, Q6P3V2, Q6P5C7, Q6ZN57, Q86UE3, Q86XN6, Q86YE8, Q8C827, Q8IYB9, Q8N4W9, Q8N7M2

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — NPC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1113 predictions. Top by Δscore:

Variant	Effect	Δscore
19:19915367:A:T	donor_gain	1.0000
19:19933180:A:AG	acceptor_gain	1.0000
19:19933181:G:GA	acceptor_gain	1.0000
19:19933181:GTT:G	acceptor_gain	1.0000
19:19933181:GTTA:G	acceptor_gain	1.0000
19:19933181:GTTAT:G	acceptor_gain	1.0000
19:19901399:G:T	donor_gain	0.9900
19:19901435:G:T	donor_gain	0.9900
19:19915271:GTTTT:G	acceptor_loss	0.9900
19:19915272:TTTTT:T	acceptor_loss	0.9900
19:19915273:TTTTC:T	acceptor_loss	0.9900
19:19915274:TTTCA:T	acceptor_loss	0.9900
19:19915275:TTCA:T	acceptor_loss	0.9900
19:19915277:CAG:C	acceptor_loss	0.9900
19:19915278:A:AG	acceptor_gain	0.9900
19:19915278:AG:A	acceptor_gain	0.9900
19:19915279:G:GG	acceptor_gain	0.9900
19:19915279:G:T	acceptor_loss	0.9900
19:19915279:GG:G	acceptor_gain	0.9900
19:19915279:GGGA:G	acceptor_gain	0.9900
19:19915279:GGGAC:G	acceptor_gain	0.9900
19:19915388:A:AG	donor_gain	0.9900
19:19915389:G:GG	donor_gain	0.9900
19:19915402:CCTTG:C	donor_loss	0.9900
19:19915405:TGGTG:T	donor_loss	0.9900
19:19915407:G:GA	donor_loss	0.9900
19:19915407:G:GG	donor_gain	0.9900
19:19915408:T:TT	donor_loss	0.9900
19:19915409:GAGGA:G	donor_loss	0.9900
19:19915412:GA:G	donor_gain	0.9900

AlphaMissense

4130 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:19933751:T:C	F266L	0.988
19:19933753:T:A	F266L	0.988
19:19933753:T:G	F266L	0.988
19:19933835:T:C	F294L	0.985
19:19933837:T:A	F294L	0.985
19:19933837:T:G	F294L	0.985
19:19934675:T:C	F574L	0.985
19:19934677:T:A	F574L	0.985
19:19934677:T:G	F574L	0.985
19:19933667:T:C	F238L	0.984
19:19933669:T:A	F238L	0.984
19:19933669:T:G	F238L	0.984
19:19934003:T:C	F350L	0.983
19:19934005:T:A	F350L	0.983
19:19934005:T:G	F350L	0.983
19:19934507:T:C	F518L	0.983
19:19934509:T:A	F518L	0.983
19:19934509:T:G	F518L	0.983
19:19934591:T:C	F546L	0.983
19:19934593:T:A	F546L	0.983
19:19934593:T:G	F546L	0.983
19:19934255:T:C	F434L	0.982
19:19934257:T:A	F434L	0.982
19:19934257:T:G	F434L	0.982
19:19933919:T:C	F322L	0.981
19:19933921:T:A	F322L	0.981
19:19933921:T:G	F322L	0.981
19:19934423:T:C	F490L	0.980
19:19934425:T:A	F490L	0.980
19:19934425:T:G	F490L	0.980

dbSNP variants (sampled 300 via entrez): RS1000001170 (19:19927339 C>G,T), RS1000053983 (19:19922077 G>A), RS1000096543 (19:19919416 G>A,T), RS1000165185 (19:19928274 C>G), RS1000245211 (19:19905409 C>G), RS1000311820 (19:19924725 G>C,T), RS1000422850 (19:19934757 C>G), RS1000489511 (19:19930636 TCTCA>T), RS1000510537 (19:19921534 T>C), RS1000564559 (19:19902098 T>TTTA), RS1000627455 (19:19900474 G>A,C), RS1000690769 (19:19908063 C>A), RS1000932494 (19:19913569 T>A), RS1001006574 (19:19920314 G>C), RS1001186044 (19:19907192 T>C)

Disease associations

OMIM: gene MIM:603975 | 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
GCST000349_21	Smoking behavior	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	8
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Cisplatin	decreases response to substance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
hydroxyhydroquinone	decreases expression	1
arsenite	decreases expression	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
PM 00104	decreases response to substance	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Trabectedin	decreases response to substance	1

Clinical trials (associated diseases)

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