ZNF404

Summary

ZNF404 (zinc finger protein 404, HGNC:19417) is a protein-coding gene on chromosome 19q13.31, encoding Zinc finger protein 404 (Q494X3). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 342908 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_001033719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19417
Approved symbol	ZNF404
Name	zinc finger protein 404
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176222
Ensembl biotype	protein_coding
Entrez	342908

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000587128, ENST00000587539, ENST00000588094, ENST00000591815, ENST00000850976, ENST00000950358

RefSeq mRNA: 1 — MANE Select: NM_001033719 NM_001033719

CCDS: CCDS59394

Canonical transcript exons

ENST00000587539 — 3 exons

Exon	Start	End
ENSE00002771034	43880010	43880136
ENSE00002856668	43872365	43874077
ENSE00002863473	43883956	43883964

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 88.67.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	88.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.35	gold quality
adenohypophysis	UBERON:0002196	85.07	gold quality
pituitary gland	UBERON:0000007	83.95	gold quality
apex of heart	UBERON:0002098	83.50	gold quality
spinal cord	UBERON:0002240	83.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.50	gold quality
stromal cell of endometrium	CL:0002255	82.48	gold quality
cerebellar hemisphere	UBERON:0002245	82.30	gold quality
cerebellar cortex	UBERON:0002129	82.01	gold quality
ventricular zone	UBERON:0003053	81.68	gold quality
right atrium auricular region	UBERON:0006631	81.29	gold quality
right frontal lobe	UBERON:0002810	81.12	gold quality
ganglionic eminence	UBERON:0004023	80.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.86	gold quality
heart left ventricle	UBERON:0002084	80.81	gold quality
cerebellum	UBERON:0002037	79.97	gold quality
caudate nucleus	UBERON:0001873	79.92	gold quality
cardiac ventricle	UBERON:0002082	79.68	gold quality
cardiac atrium	UBERON:0002081	79.60	gold quality
hypothalamus	UBERON:0001898	78.96	gold quality
anterior cingulate cortex	UBERON:0009835	78.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.95	gold quality
left ovary	UBERON:0002119	78.85	gold quality
nucleus accumbens	UBERON:0001882	78.82	gold quality
amygdala	UBERON:0001876	78.28	gold quality
heart	UBERON:0000948	78.12	gold quality
right ovary	UBERON:0002118	77.44	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting ZNF404, 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-548C-3P	99.99	74.01	7587
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-455-5P	98.74	67.31	795
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-1227-3P	97.36	66.94	834

Literature-anchored findings (GeneRIF, showing 2)

• The deleterious SNPs localized in STXBP4 and ZNF404 genes were identified which might play a role in breast cancer development by dysregulating its gene expression. (PMID:28422318)
• We used The Cancer Genome Atlas breast cancer patient data to identify ANKLE1 and ZNF404 as the target genes of candidate TF binding site SNPs in the 19p13.11 and 19q13.31 GWAS-identified loci. These SNPs are associated with the expression of ZNF404 and ANKLE1 in breast tissue. (PMID:28957321)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF582 (ENSG00000018869), ZNF264 (ENSG00000083844), ZNF343 (ENSG00000088876), ZNF684 (ENSG00000117010), ZNF133 (ENSG00000125846), ZNF557 (ENSG00000130544), ZNF337 (ENSG00000130684), ZNF20 (ENSG00000132010), ZFP37 (ENSG00000136866), ZNF614 (ENSG00000142556), KRBOX4 (ENSG00000147121), ZNF599 (ENSG00000153896), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF558 (ENSG00000167785), ZNF35 (ENSG00000169981), ZNF778 (ENSG00000170100), ZNF439 (ENSG00000171291), ZNF440 (ENSG00000171295), ZNF556 (ENSG00000172000), ZNF554 (ENSG00000172006), ZNF596 (ENSG00000172748), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF491 (ENSG00000177599), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF875 (ENSG00000181666), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300), ZNF70 (ENSG00000187792)

Protein

Protein identifiers

Zinc finger protein 404 — Q494X3 (reviewed: Q494X3)

All UniProt accessions (1): Q494X3

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_001028891* (*=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
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF01352, PF13912

UniProt features (19 total): zinc finger region 15, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q494X3-F1	73.17	0.25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GCM_MAP4K4, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, SENESE_HDAC3_TARGETS_DN, GOCC_NUCLEOLUS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, BAHD1_TARGET_GENES, CBX5_TARGET_GENES, ZBTB12_TARGET_GENES, ZFP3_TARGET_GENES, ZNF30_TARGET_GENES, ZNF329_TARGET_GENES

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

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)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
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

322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF404	FLACC1	Q96Q35	480
ZNF404	ATP6AP1L	Q52LC2	477
ZNF404	LRRC37A2	A6NM11	446
ZNF404	STXBP4	Q6ZWJ1	445
ZNF404	CUL7	Q14999	427
ZNF404	PLEKHD1	A6NEE1	414
ZNF404	LRRC37A	A6NMS7	414
ZNF404	LRRC37A3	O60309	401
ZNF404	L3MBTL3	Q96JM7	398
ZNF404	ANKLE1	Q8NAG6	394
ZNF404	ABHD8	Q96I13	378
ZNF404	LIMS3	P0CW19	375
ZNF404	ANKRD34A	Q69YU3	373
ZNF404	RCCD1	A6NED2	358
ZNF404	NUDT17	P0C025	348
ZNF404	KRTAP1-5	Q9BYS1	348

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MEOX2	ZNF404	psi-mi:“MI:0915”(physical association)	0.560
ZNF404	MEOX2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (2): ZNF404 (Two-hybrid), ZNF404 (Affinity Capture-MS)

ESM2 similar proteins: A2RRD8, A6NHJ4, B4DX44, O75346, P10077, P10755, P15621, P16372, P16373, P51786, P52737, P85977, Q0VGE8, Q14588, Q147U1, Q15928, Q15973, Q2M3X9, Q3KNS6, Q3MIS6, Q494X3, Q5HY98, Q5RBQ3, Q5REK1, Q5VIY5, Q60585, Q61751, Q6GQR8, Q7L2R6, Q7TSH9, Q8IYX0, Q8N782, Q8N823, Q8N988, Q8N9F8, Q8NA42, Q8NCK3, Q8NDP4, Q8NEP9, Q8TC21

Diamond homologs: A0JPK3, A8MT65, C9JN71, E9QAG8, G3X9G7, O75820, P16373, P16374, P16415, P17017, P17024, P17025, P51815, P52737, Q08AG5, Q08ER8, Q0D2J5, Q15973, Q2M218, Q3KP31, Q3V080, Q494X3, Q4R4C7, Q5MYW4, Q5R9F0, Q5R9S5, Q5REI6, Q5REK1, Q68EA5, Q6P560, Q6P5C7, Q6ZQV5, Q7L945, Q86T29, Q8BGV5, Q8C6P8, Q8IYI8, Q8IZC7, Q8N7K0, Q8N972

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

455 predictions. Top by Δscore:

Variant	Effect	Δscore
19:43874078:C:CC	acceptor_gain	0.9800
19:43880008:AC:A	donor_gain	0.9800
19:43880009:CC:C	donor_gain	0.9800
19:43880137:C:CG	acceptor_loss	0.9800
19:43880004:TCTTA:T	donor_loss	0.9700
19:43880005:CT:C	donor_loss	0.9700
19:43880006:T:TA	donor_loss	0.9700
19:43880007:TACC:T	donor_loss	0.9700
19:43880008:A:AC	donor_gain	0.9700
19:43880008:ACC:A	donor_loss	0.9700
19:43880009:C:CA	donor_loss	0.9700
19:43880009:C:CC	donor_gain	0.9700
19:43880139:G:C	acceptor_loss	0.9700
19:43880140:AAATG:A	acceptor_loss	0.9700
19:43880141:AATGA:A	acceptor_loss	0.9700
19:43880142:A:C	acceptor_loss	0.9700
19:43874074:AAGTC:A	acceptor_loss	0.9600
19:43874075:AGTC:A	acceptor_loss	0.9600
19:43874076:GTCT:G	acceptor_loss	0.9600
19:43874077:TCTG:T	acceptor_loss	0.9600
19:43874078:C:T	acceptor_loss	0.9600
19:43874079:T:A	acceptor_loss	0.9600
19:43880002:ATTCT:A	donor_loss	0.9600
19:43880003:TTCTT:T	donor_loss	0.9600
19:43880147:A:T	acceptor_loss	0.9600
19:43881190:ACT:A	donor_gain	0.9600
19:43881191:CTC:C	donor_gain	0.9600
19:43881192:TCT:T	donor_gain	0.9600
19:43881193:CTC:C	donor_gain	0.9600
19:43874073:AAAGT:A	acceptor_gain	0.9500

AlphaMissense

3724 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:43873542:A:C	F224L	0.997
19:43873542:A:T	F224L	0.997
19:43873544:A:G	F224L	0.997
19:43873374:A:C	F280L	0.996
19:43873374:A:T	F280L	0.996
19:43873376:A:G	F280L	0.996
19:43872786:A:C	F476L	0.995
19:43872786:A:T	F476L	0.995
19:43872788:A:G	F476L	0.995
19:43872954:G:C	F420L	0.995
19:43872954:G:T	F420L	0.995
19:43872956:A:G	F420L	0.995
19:43873290:A:C	F308L	0.995
19:43873290:A:T	F308L	0.995
19:43873292:A:G	F308L	0.995
19:43873038:A:C	F392L	0.994
19:43873038:A:T	F392L	0.994
19:43873040:A:G	F392L	0.994
19:43873122:A:C	F364L	0.994
19:43873122:A:T	F364L	0.994
19:43873124:A:G	F364L	0.994
19:43873206:A:C	F336L	0.994
19:43873206:A:T	F336L	0.994
19:43873208:A:G	F336L	0.994
19:43872870:A:C	F448L	0.993
19:43872870:A:T	F448L	0.993
19:43872872:A:G	F448L	0.993
19:43872702:A:C	F504L	0.992
19:43872702:A:T	F504L	0.992
19:43872704:A:G	F504L	0.992

dbSNP variants (sampled 300 via entrez): RS1000214616 (19:43880670 G>A,C), RS1000632499 (19:43882287 C>A,T), RS1000660408 (19:43881900 T>A,G), RS1001015665 (19:43885889 T>C), RS1001186144 (19:43875005 T>C), RS1001885494 (19:43882385 C>G), RS1002026621 (19:43874441 A>G), RS1002553104 (19:43885818 T>C), RS1002576431 (19:43871932 A>T), RS1002728666 (19:43878464 T>C), RS1002774968 (19:43877586 A>T), RS1003181231 (19:43884667 T>C,G), RS1003236702 (19:43877014 G>A), RS1003556727 (19:43884147 T>C), RS1003832202 (19:43875994 G>T)

Disease associations

OMIM: gene `` | 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
GCST002522_1	Reading or mathematical ability	8.000000e-09
GCST90014033_73	Haemorrhoidal disease	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005229	reading

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
Benzo(a)pyrene	increases expression, increases methylation	2
Nickel	decreases expression	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
zinc chromate	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
monomethylarsonous acid	increases expression	1
NSC 689534	affects binding, increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, increases expression	1
Cadmium	decreases expression	1
Copper	affects binding, increases expression	1
Folic Acid	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin M1	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XW42	HEK293 eGFP-ZNF404	Transformed cell line	Female

Clinical trials (associated diseases)

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