ZNF418

Summary

ZNF418 (zinc finger protein 418, HGNC:20647) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger protein 418 (Q8TF45). Transcriptional repressor.

Enables DNA-binding transcription repressor activity. Predicted to be involved in microautophagy; regulation of proteasomal ubiquitin-dependent protein catabolic process; and regulation of transcription by RNA polymerase II. Is active in nucleus.

Source: NCBI Gene 147686 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 117 total — 1 likely-pathogenic
• MANE Select transcript: NM_133460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20647
Approved symbol	ZNF418
Name	zinc finger protein 418
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1956, FLJ31551
Ensembl gene	ENSG00000196724
Ensembl biotype	protein_coding
OMIM	619509
Entrez	147686

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000396147, ENST00000425570, ENST00000593296, ENST00000595569, ENST00000595830, ENST00000598213, ENST00000599086, ENST00000599852, ENST00000600353, ENST00000600989, ENST00000601593, ENST00000616958

RefSeq mRNA: 5 — MANE Select: NM_133460 NM_001317027, NM_001317028, NM_001317029, NM_001317030, NM_133460

CCDS: CCDS42642, CCDS82409, CCDS82410

Canonical transcript exons

ENST00000396147 — 6 exons

Exon	Start	End
ENSE00001432987	57935161	57935402
ENSE00001524053	57925623	57928047
ENSE00002503815	57930428	57930554
ENSE00003476772	57923192	57923289
ENSE00003511624	57933817	57933902
ENSE00003903476	57921882	57922629

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 89.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.7366 / max 91.0908, expressed in 1087 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182920	3.7366	1087

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.57	gold quality
cortical plate	UBERON:0005343	89.06	gold quality
buccal mucosa cell	CL:0002336	88.72	silver quality
ganglionic eminence	UBERON:0004023	88.61	gold quality
ventricular zone	UBERON:0003053	88.02	gold quality
apex of heart	UBERON:0002098	86.97	gold quality
oviduct epithelium	UBERON:0004804	86.67	gold quality
cerebellar hemisphere	UBERON:0002245	86.52	gold quality
cerebellar cortex	UBERON:0002129	86.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.25	gold quality
cerebellum	UBERON:0002037	84.43	gold quality
right uterine tube	UBERON:0001302	84.41	gold quality
pancreatic ductal cell	CL:0002079	84.35	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.25	gold quality
right lobe of thyroid gland	UBERON:0001119	84.21	gold quality
left lobe of thyroid gland	UBERON:0001120	84.00	gold quality
thyroid gland	UBERON:0002046	83.16	gold quality
colonic epithelium	UBERON:0000397	83.03	gold quality
tibialis anterior	UBERON:0001385	83.02	silver quality
heart left ventricle	UBERON:0002084	82.20	gold quality
right atrium auricular region	UBERON:0006631	82.20	gold quality
adenohypophysis	UBERON:0002196	82.13	gold quality
cardiac ventricle	UBERON:0002082	81.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.26	gold quality
left ovary	UBERON:0002119	81.15	gold quality
cardiac atrium	UBERON:0002081	81.06	gold quality
right frontal lobe	UBERON:0002810	80.37	gold quality
heart	UBERON:0000948	80.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.02	gold quality
pituitary gland	UBERON:0000007	79.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.93

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1980.1	ZNF418	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:28273063

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

45 targeting ZNF418, 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-3925-3P	100.00	69.95	1237
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-4279	99.19	66.70	2437

Literature-anchored findings (GeneRIF, showing 4)

• These results suggest that ZNF418 is a member of the zincfinger transcription factor family and may act as a negative regulator in MAPK signaling pathway. (PMID:18084723)
• the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro (PMID:29065170)
• Integration analysis of esophageal squamous cell carcinoma (ESCC) identified five hyper-methylated CpG sites in STK3, ZNF418 and ZNF542 that can be used for effective methylation-based testing for ESCC diagnosis. (PMID:29270239)
• A high-throughput screening identifies ZNF418 as a novel regulator of the ubiquitin-proteasome system and autophagy-lysosomal pathway. (PMID:33249983)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfx	ENSDARG00000074453
danio_rerio		ENSDARG00000098424
mus_musculus	Zfy2	ENSMUSG00000000103
mus_musculus	Zfy1	ENSMUSG00000053211
rattus_norvegicus	Zfy1	ENSRNOG00000053042

Paralogs (38): ZFX (ENSG00000005889), ZBTB11 (ENSG00000066422), ZFAT (ENSG00000066827), ZFY (ENSG00000067646), ZNF586 (ENSG00000083828), IKZF5 (ENSG00000095574), ZNF419 (ENSG00000105136), ZNF549 (ENSG00000121406), ZSCAN20 (ENSG00000121903), ZNF304 (ENSG00000131845), PRDM15 (ENSG00000141956), ZNF660 (ENSG00000144792), ZNF711 (ENSG00000147180), ZNF773 (ENSG00000152439), ZNF256 (ENSG00000152454), ZNF837 (ENSG00000152475), ZNF691 (ENSG00000164011), ZNF610 (ENSG00000167554), E4F1 (ENSG00000167967), ZNF562 (ENSG00000171466), ZNF561 (ENSG00000171469), ZNF584 (ENSG00000171574), ZIK1 (ENSG00000171649), ZNF570 (ENSG00000171827), ZSCAN2 (ENSG00000176371), ZNF552 (ENSG00000178935), ZNF154 (ENSG00000179909), ZNF792 (ENSG00000180884), ZNF793 (ENSG00000188227), ZNF548 (ENSG00000188785), ZNF79 (ENSG00000196152), ZNF772 (ENSG00000197128), ZNF583 (ENSG00000198440), ZNF480 (ENSG00000198464), ZNF551 (ENSG00000204519), ZNF134 (ENSG00000213762), ZNF587B (ENSG00000269343), ZNF8 (ENSG00000278129)

Protein

Protein identifiers

Zinc finger protein 418 — Q8TF45 (reviewed: Q8TF45)

All UniProt accessions (7): Q8TF45, J3KQR4, M0QX21, M0QX82, M0QXB3, M0QYW9, M0R1R2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. May play a role as regulator of the ubiquitin-proteasome system and autophagy-lysosomal pathway.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in heart.

Domain organisation. The KRAB domain mediates the transcription repressor activity.

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

RefSeq proteins (5): NP_001303956, NP_001303957, NP_001303958, NP_001303959, NP_597717* (*=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 (19 total): zinc finger region 16, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF45-F1	71.18	0.27

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: 61 (showing top): GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEOLYSIS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEOLYSIS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PROCESS_UTILIZING_AUTOPHAGIC_MECHANISM, GOBP_REGULATION_OF_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), microautophagy (GO:0016237), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), regulation of DNA-templated transcription (GO:0006355), 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), DNA-binding transcription repressor activity (GO:0001217), zinc ion binding (GO:0008270), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), 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	3
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-binding transcription factor activity	2
transcription cis-regulatory region binding	2
transcription by RNA polymerase II	1
autophagy	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
regulation of proteasomal protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
transition metal ion binding	1
nucleic acid binding	1
transcription regulator activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF418	LHFPL7	Q6ICI0	557
ZNF418	Q6GMV1	Q6GMV1	528
ZNF418	VMA22	Q96NT0	463
ZNF418	DQX1	Q8TE96	447
ZNF418	AGAP4	Q96P64	371
ZNF418	C12orf42	Q96LP6	370
ZNF418	CCDC183	Q5T5S1	366
ZNF418	PPP2R5C	Q13362	364
ZNF418	FAM89B	Q8N5H3	356
ZNF418	TRIM61	Q5EBN2	354
ZNF418	POTEI	P0CG38	352
ZNF418	KRTAP1-5	Q9BYS1	350
ZNF418	PPP1R37	O75864	348
ZNF418	POTEJ	P0CG39	348
ZNF418	SLC66A2	Q8N2U9	340

IntAct

10 interactions, top by confidence:

A	B	Type	Score
KRTAP10-7	ZNF418	psi-mi:“MI:0915”(physical association)	0.560
ZNF418	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	ZNF418	psi-mi:“MI:0915”(physical association)	0.560
ECE1	ZNF418	psi-mi:“MI:0915”(physical association)	0.370
ZNF418	ZNF195	psi-mi:“MI:0914”(association)	0.350
ZNF418	KRTAP10-6	psi-mi:“MI:0915”(physical association)	0.000
ZNF418	PAK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): KRTAP10-7 (Two-hybrid), ZNF418 (Two-hybrid), ZNF195 (Affinity Capture-MS), TBC1D14 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), PTPN4 (Affinity Capture-MS), GPCPD1 (Affinity Capture-MS), TRIM33 (Affinity Capture-MS), CENPB (Affinity Capture-MS), ZNF845 (Affinity Capture-MS), ZYG11A (Affinity Capture-MS), VILL (Affinity Capture-MS), TGM4 (Affinity Capture-MS), USP34 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS)

ESM2 similar proteins: A6NDX5, A8MQ14, B7Z6K7, C9JN71, O43361, P0CJ79, P0DKX0, P17017, P17021, P17027, P17035, P17039, P51522, Q02386, Q13106, Q14585, Q3SYV7, Q3ZCX4, Q4R4C7, Q4V348, Q52M93, Q5R9F0, Q5RB30, Q5SXM1, Q6P3V2, Q6P5C7, Q6P9A1, Q6PDB4, Q6ZN06, Q6ZN08, Q6ZN57, Q76KX8, Q7Z340, Q86V71, Q86XN6, Q8N4W9, Q8N7Q3, Q8N8Z8, Q8TC21, Q8TF45

Diamond homologs: A2RRD8, A6NFI3, A6NM28, A8MUZ8, A8MWA4, B2RUI1, B4DU55, E9Q8G5, O43296, O43361, O75467, O75820, P0CH99, P0CI00, P10078, P16373, P16374, P17021, P17023, P17032, P17097, P17098, P21506, P51786, P52740, Q06732, Q08ER8, Q13106, Q13360, Q13398, Q14592, Q147U1, Q32M78, Q3KQV3, Q3MIS6, Q3SY52, Q571J5, Q5CZA5, Q5HY98, Q5R7I8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	101
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
982221	NM_133460.3(ZNF418):c.1757C>T (p.Thr586Ile)	Likely pathogenic

SpliceAI

835 predictions. Top by Δscore:

Variant	Effect	Δscore
19:57928044:CAAC:C	acceptor_gain	0.9900
19:57928046:ACCT:A	acceptor_loss	0.9900
19:57928047:CCTG:C	acceptor_loss	0.9900
19:57928048:CTGAA:C	acceptor_loss	0.9900
19:57928049:T:A	acceptor_loss	0.9900
19:57922509:C:T	acceptor_gain	0.9800
19:57930553:CCCTG:C	acceptor_gain	0.9800
19:57930554:CCTGC:C	acceptor_gain	0.9800
19:57933853:T:TA	donor_gain	0.9800
19:57933812:CTCA:C	donor_loss	0.9700
19:57933813:TCACC:T	donor_loss	0.9700
19:57933814:CACCT:C	donor_loss	0.9700
19:57933815:A:C	donor_loss	0.9700
19:57933816:C:CA	donor_loss	0.9700
19:57928048:C:CC	acceptor_gain	0.9600
19:57930555:CTG:C	acceptor_gain	0.9500
19:57930558:C:CC	acceptor_gain	0.9400
19:57922310:G:T	acceptor_gain	0.9300
19:57922509:C:CT	acceptor_gain	0.9300
19:57933849:T:TA	donor_gain	0.9300
19:57922627:TCC:T	acceptor_gain	0.9200
19:57922628:CCC:C	acceptor_gain	0.9200
19:57925614:ACTAC:A	donor_loss	0.9200
19:57925615:CTACT:C	donor_loss	0.9200
19:57925616:TAC:T	donor_loss	0.9200
19:57925617:ACT:A	donor_loss	0.9200
19:57925618:CTCAC:C	donor_loss	0.9200
19:57925619:T:TA	donor_loss	0.9200
19:57925620:C:CC	donor_loss	0.9200
19:57925621:A:AG	donor_loss	0.9200

AlphaMissense

4482 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:57926960:A:C	F407L	0.997
19:57926960:A:T	F407L	0.997
19:57926962:A:G	F407L	0.997
19:57927212:A:C	F323L	0.997
19:57927212:A:T	F323L	0.997
19:57927214:A:G	F323L	0.997
19:57926876:A:C	F435L	0.996
19:57926876:A:T	F435L	0.996
19:57926878:A:G	F435L	0.996
19:57927296:A:C	F295L	0.996
19:57927296:A:T	F295L	0.996
19:57927298:A:G	F295L	0.996
19:57927128:A:C	F351L	0.995
19:57927128:A:T	F351L	0.995
19:57927130:A:G	F351L	0.995
19:57927380:A:C	F267L	0.995
19:57927380:A:T	F267L	0.995
19:57927382:A:G	F267L	0.995
19:57927044:A:C	F379L	0.994
19:57927044:A:T	F379L	0.994
19:57927046:A:G	F379L	0.994
19:57926540:A:C	F547L	0.993
19:57926540:A:T	F547L	0.993
19:57926542:A:G	F547L	0.993
19:57926624:A:C	F519L	0.993
19:57926624:A:T	F519L	0.993
19:57926626:A:G	F519L	0.993
19:57926708:A:C	F491L	0.992
19:57926708:A:T	F491L	0.992
19:57926710:A:G	F491L	0.992

dbSNP variants (sampled 300 via entrez): RS1000217064 (19:57937054 C>T), RS1000327425 (19:57931763 A>G), RS1000587079 (19:57936541 A>G), RS1000652441 (19:57936755 C>T), RS1000831816 (19:57923243 G>A), RS1000956718 (19:57928054 G>A), RS1001389363 (19:57927825 A>G,T), RS1001416865 (19:57922201 C>T), RS1001459970 (19:57932110 T>C), RS1001624383 (19:57925579 C>T), RS1001995482 (19:57935349 A>T), RS1002038811 (19:57925416 A>C,G), RS1002100790 (19:57930486 A>C), RS1002206312 (19:57931820 C>A), RS1002282592 (19:57935525 G>C)

Disease associations

OMIM: gene MIM:619509 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Moyamoya angiopathy (Orphanet:477768)

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	3
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
bisphenol A	increases methylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
perfluorooctane sulfonic acid	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
bisphenol S	decreases methylation	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Nickel	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	increases expression	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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