ZNF684

Summary

ZNF684 (zinc finger protein 684, HGNC:28418) is a protein-coding gene on chromosome 1p34.2, encoding Zinc finger protein 684 (Q5T5D7). May be involved in transcriptional regulation.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within innate immune response and negative regulation of single stranded viral RNA replication via double stranded DNA intermediate. Predicted to be active in nucleus.

Source: NCBI Gene 127396 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_152373

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28418
Approved symbol	ZNF684
Name	zinc finger protein 684
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC27466
Ensembl gene	ENSG00000117010
Ensembl biotype	protein_coding
Entrez	127396

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 22 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000372696, ENST00000372697, ENST00000372699, ENST00000465152, ENST00000472043, ENST00000493756, ENST00000648542, ENST00000900101, ENST00000900102, ENST00000900103, ENST00000900104, ENST00000900105, ENST00000900106, ENST00000900107, ENST00000900108, ENST00000900109, ENST00000900110, ENST00000900111, ENST00000900112, ENST00000900113, ENST00000900114, ENST00000921959, ENST00000921960, ENST00000944562, ENST00000944563

RefSeq mRNA: 1 — MANE Select: NM_152373 NM_152373

CCDS: CCDS454

Canonical transcript exons

ENST00000372699 — 5 exons

Exon	Start	End
ENSE00001250695	40531637	40531787
ENSE00001458418	40546562	40548167
ENSE00003481585	40533143	40533181
ENSE00003543009	40541615	40541710
ENSE00003583917	40540586	40540712

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 86.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.7059 / max 139.6092, expressed in 1463 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2393	3.1365	1380
2394	0.5482	291
2395	0.0212	6

Top tissues by expression

245 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	86.10	gold quality
right lobe of liver	UBERON:0001114	83.32	gold quality
apex of heart	UBERON:0002098	82.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.38	gold quality
calcaneal tendon	UBERON:0003701	79.65	gold quality
adrenal tissue	UBERON:0018303	78.41	gold quality
metanephros cortex	UBERON:0010533	77.56	gold quality
liver	UBERON:0002107	77.48	gold quality
heart left ventricle	UBERON:0002084	76.30	gold quality
right atrium auricular region	UBERON:0006631	76.00	gold quality
left adrenal gland	UBERON:0001234	75.76	gold quality
stromal cell of endometrium	CL:0002255	75.72	gold quality
right adrenal gland	UBERON:0001233	75.58	gold quality
right adrenal gland cortex	UBERON:0035827	75.49	gold quality
cardiac ventricle	UBERON:0002082	75.21	gold quality
left adrenal gland cortex	UBERON:0035825	75.06	gold quality
monocyte	CL:0000576	74.79	gold quality
leukocyte	CL:0000738	74.73	gold quality
islet of Langerhans	UBERON:0000006	74.73	gold quality
cardiac atrium	UBERON:0002081	74.30	gold quality
adrenal gland	UBERON:0002369	74.17	gold quality
heart	UBERON:0000948	73.99	gold quality
rectum	UBERON:0001052	73.92	gold quality
body of pancreas	UBERON:0001150	73.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.60	gold quality
smooth muscle tissue	UBERON:0001135	73.33	gold quality
adult mammalian kidney	UBERON:0000082	73.26	gold quality
cortex of kidney	UBERON:0001225	73.18	gold quality
pancreas	UBERON:0001264	73.02	gold quality
granulocyte	CL:0000094	72.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.70

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1600.1	ZNF684	More than 3 adjacent zinc fingers
MA1600.2	ZNF684	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:25690854

miRNA regulators (miRDB)

58 targeting ZNF684, 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-3924	100.00	72.09	2394
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4743-3P	99.62	68.12	2095

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), 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), ZNF404 (ENSG00000176222), 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 684 — Q5T5D7 (reviewed: Q5T5D7)

All UniProt accessions (3): Q5T5D7, Q5T5D8, Q5T5D9

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_689586* (*=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
IPR050758	Znf_C2H2-type	Family

Pfam: PF00096, PF01352

UniProt features (10 total): zinc finger region 8, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T5D7-F1	72.80	0.18

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 52 (showing top): chr1p34, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, FISCHER_DREAM_TARGETS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, ZWANG_DOWN_BY_2ND_EGF_PULSE, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, BARX1_TARGET_GENES, ELF2_TARGET_GENES, HHEX_TARGET_GENES, HOXB4_TARGET_GENES, NKX2_2_TARGET_GENES, OVOL3_TARGET_GENES, TEAD2_TARGET_GENES, ZFHX3_TARGET_GENES, ZFP91_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), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

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

Protein interactions and networks

STRING

318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF684	CCDC17	Q96LX7	628
ZNF684	OR5AP2	Q8NGF4	579
ZNF684	OR8B4	Q96RC9	574
ZNF684	PHETA1	Q8N4B1	543
ZNF684	FBXO48	Q5FWF7	543
ZNF684	FOXD4L6	Q3SYB3	543
ZNF684	OR1L8	Q8NGR8	543
ZNF684	BHLHA9	Q7RTU4	511
ZNF684	OR2I1	Q8NGU4	495
ZNF684	OR4D10	Q8NGI6	465
ZNF684	CCDC127	Q96BQ5	455
ZNF684	NUP62CL	Q9H1M0	449
ZNF684	KLHL5	Q96PQ7	442
ZNF684	BRINP3	Q76B58	398
ZNF684	GEMIN8	Q9NWZ8	370

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
ZNF684	GAPDHS	psi-mi:“MI:0914”(association)	0.350
ZNF684	PIN1	psi-mi:“MI:0914”(association)	0.350
	ZNF684	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): ZNF684 (Reconstituted Complex), GAPDHS (Affinity Capture-MS), POTEE (Affinity Capture-MS), MTMR4 (Affinity Capture-MS), RABL6 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), PHYKPL (Affinity Capture-MS), ZNF684 (Biochemical Activity), TRIM28 (Affinity Capture-MS), MTMR4 (Affinity Capture-MS), POTEE (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), PHYKPL (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), ZNF684 (Affinity Capture-MS)

ESM2 similar proteins: A0JPL0, A3KN36, A7MBI1, A8MT65, B2RXC5, D3ZVT0, P08042, P21506, P51508, P52738, Q02525, Q06730, Q12901, Q2KI58, Q2M218, Q2M3W8, Q2M3X9, Q2VY69, Q49AA0, Q4R6J4, Q4V8A8, Q5FWF6, Q5HY98, Q5RB33, Q5RC79, Q5REF1, Q5T5D7, Q5VIY5, Q61967, Q6P2D0, Q6ZN11, Q86XU0, Q86Y25, Q8N782, Q8N859, Q8NB42, Q8TF39, Q8TF47, Q8WXB4, Q95K49

Diamond homologs: A0A1W2PQL4, A0JNB1, A0JPL0, A6NK53, A6QLU5, A6QPT6, A7MBI1, A8MT65, A8MUV8, A8MWA4, B2RXC5, B4DU55, B4DX44, E9PYI1, O14628, O75346, P0CH99, P0CI00, P17014, P17030, P17032, P17098, P51786, P85977, Q02386, Q06730, Q06732, Q0VAW7, Q12901, Q13360, Q14586, Q14588, Q14590, Q16587, Q2M3X9, Q2VY69, Q32M78, Q3ZCX4, Q49AA0, Q4R6J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1067 predictions. Top by Δscore:

Variant	Effect	Δscore
1:40540709:GTGG:G	donor_gain	1.0000
1:40540718:GACAA:G	donor_gain	1.0000
1:40531689:G:GT	donor_gain	0.9900
1:40531770:G:GT	donor_gain	0.9900
1:40531785:CAGGT:C	donor_loss	0.9900
1:40531786:AGGTA:A	donor_loss	0.9900
1:40531787:GG:G	donor_loss	0.9900
1:40540536:A:G	acceptor_gain	0.9900
1:40540708:AGTGG:A	donor_loss	0.9900
1:40540711:GG:G	donor_gain	0.9900
1:40540712:GG:G	donor_gain	0.9900
1:40540715:AAG:A	donor_loss	0.9900
1:40531656:AGCC:A	donor_gain	0.9800
1:40531657:GCCG:G	donor_gain	0.9800
1:40531689:G:T	donor_gain	0.9800
1:40531782:TGGC:T	donor_gain	0.9800
1:40541614:GGAT:G	acceptor_gain	0.9800
1:40546560:A:AG	acceptor_gain	0.9800
1:40546561:G:GG	acceptor_gain	0.9800
1:40540713:G:GG	donor_gain	0.9700
1:40531644:T:TA	donor_gain	0.9600
1:40531645:A:AA	donor_gain	0.9600
1:40541708:CAGG:C	donor_loss	0.9600
1:40541710:GGTG:G	donor_loss	0.9600
1:40541711:G:A	donor_loss	0.9600
1:40541712:T:A	donor_loss	0.9600
1:40541713:GAGT:G	donor_loss	0.9600
1:40546556:TTTTA:T	acceptor_loss	0.9600
1:40546557:TTTAG:T	acceptor_loss	0.9600
1:40546558:TTAG:T	acceptor_loss	0.9600

AlphaMissense

2544 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:40546993:T:C	F224L	0.998
1:40546995:T:A	F224L	0.998
1:40546995:T:G	F224L	0.998
1:40547245:T:C	F308L	0.998
1:40547247:T:A	F308L	0.998
1:40547247:T:G	F308L	0.998
1:40547413:T:C	F364L	0.998
1:40547415:T:A	F364L	0.998
1:40547415:T:G	F364L	0.998
1:40547077:T:C	F252L	0.997
1:40547079:C:A	F252L	0.997
1:40547079:C:G	F252L	0.997
1:40547276:A:C	Q318P	0.997
1:40547329:T:C	F336L	0.997
1:40547331:C:A	F336L	0.997
1:40547331:C:G	F336L	0.997
1:40547348:T:C	L342P	0.997
1:40547432:T:C	L370P	0.997
1:40547012:T:C	L230P	0.996
1:40547024:A:C	Q234P	0.996
1:40547161:T:C	F280L	0.996
1:40547163:C:A	F280L	0.996
1:40547163:C:G	F280L	0.996
1:40547264:T:C	L314P	0.996
1:40547360:A:C	Q346P	0.996
1:40547274:C:A	H317Q	0.995
1:40547274:C:G	H317Q	0.995
1:40547358:T:A	H345Q	0.994
1:40547358:T:G	H345Q	0.994
1:40547420:A:C	Q366P	0.994

dbSNP variants (sampled 300 via entrez): RS1000058364 (1:40541462 C>A,T), RS1000107341 (1:40536884 G>A,C), RS1000165183 (1:40543824 A>G), RS1000310434 (1:40547615 T>C), RS1000370 (1:40532734 G>A,C,T), RS1001012814 (1:40531197 C>T), RS1001362801 (1:40530654 C>T), RS1001394097 (1:40530334 G>A,C), RS1001400 (1:40533230 A>G,T), RS1001522224 (1:40538467 C>A), RS1001950741 (1:40537728 G>A,T), RS1002458560 (1:40533985 A>G,T), RS1002499885 (1:40539108 C>A,T), RS1002536068 (1:40539031 T>C), RS1003076659 (1:40545822 A>C,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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Quercetin	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
hydroquinone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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