ZNF680

Summary

ZNF680 (zinc finger protein 680, HGNC:26897) is a protein-coding gene on chromosome 7q11.21, encoding Zinc finger protein 680 (Q8NEM1). May be involved in transcriptional regulation.

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

Source: NCBI Gene 340252 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 69 total
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_178558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26897
Approved symbol	ZNF680
Name	zinc finger protein 680
Location	7q11.21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90430
Ensembl gene	ENSG00000173041
Ensembl biotype	protein_coding
Entrez	340252

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000309683, ENST00000447137, ENST00000470847, ENST00000473601, ENST00000476563, ENST00000920523, ENST00000920524, ENST00000952412

RefSeq mRNA: 2 — MANE Select: NM_178558 NM_001130022, NM_178558

CCDS: CCDS34644, CCDS47594

Canonical transcript exons

ENST00000309683 — 4 exons

Exon	Start	End
ENSE00001260770	64519878	64522500
ENSE00001920523	64562925	64563071
ENSE00002490682	64544306	64544432
ENSE00003560222	64543707	64543802

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 91.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5676 / max 244.0114, expressed in 1505 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84198	8.5553	1472
84197	1.7080	602
204457	0.3044	154

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	91.96	gold quality
adrenal tissue	UBERON:0018303	90.39	gold quality
tendon	UBERON:0000043	89.95	gold quality
corpus callosum	UBERON:0002336	88.52	gold quality
tendon of biceps brachii	UBERON:0008188	88.23	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.13	gold quality
ventricular zone	UBERON:0003053	86.62	gold quality
ganglionic eminence	UBERON:0004023	86.21	gold quality
thyroid gland	UBERON:0002046	85.47	gold quality
right adrenal gland cortex	UBERON:0035827	85.37	gold quality
left lobe of thyroid gland	UBERON:0001120	84.87	gold quality
caudate nucleus	UBERON:0001873	84.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.72	gold quality
right adrenal gland	UBERON:0001233	84.60	gold quality
adrenal gland	UBERON:0002369	84.60	gold quality
putamen	UBERON:0001874	84.46	gold quality
left adrenal gland	UBERON:0001234	84.43	gold quality
amygdala	UBERON:0001876	84.43	gold quality
nucleus accumbens	UBERON:0001882	84.27	gold quality
spinal cord	UBERON:0002240	84.16	gold quality
anterior cingulate cortex	UBERON:0009835	83.99	gold quality
left adrenal gland cortex	UBERON:0035825	83.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.77	gold quality
right lobe of thyroid gland	UBERON:0001119	83.66	gold quality
tibia	UBERON:0000979	83.62	gold quality
adrenal cortex	UBERON:0001235	83.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.44	gold quality
parietal pleura	UBERON:0002400	83.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.79

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1729.1	ZNF680	More than 3 adjacent zinc fingers
MA1729.2	ZNF680	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:27852650

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

96 targeting ZNF680, 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-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
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-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099025

Paralogs (18): ZNF430 (ENSG00000118620), ZNF92 (ENSG00000146757), ZNF66 (ENSG00000160229), ZNF22 (ENSG00000165512), ZNF114 (ENSG00000178150), ZFP41 (ENSG00000181638), ZNF730 (ENSG00000183850), ZNF479 (ENSG00000185177), ZNF626 (ENSG00000188171), ZNF431 (ENSG00000196705), ZNF100 (ENSG00000197020), ZNF257 (ENSG00000197134), ZNF98 (ENSG00000197360), ZNF675 (ENSG00000197372), ZNF273 (ENSG00000198039), ZNF737 (ENSG00000237440), ZNF253 (ENSG00000256771), ZNF723 (ENSG00000268696)

Protein

Protein identifiers

Zinc finger protein 680 — Q8NEM1 (reviewed: Q8NEM1)

All UniProt accessions (1): Q8NEM1

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NEM1-1	1	yes
Q8NEM1-2	2

RefSeq proteins (2): NP_001123494, NP_848653* (*=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, PF13912

UniProt features (20 total): zinc finger region 12, sequence variant 3, splice variant 2, chain 1, domain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEM1-F1	68.92	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 264

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: 96 (showing top): WEI_MYCN_TARGETS_WITH_E_BOX, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, FISCHER_DREAM_TARGETS, chr7q11, NUYTTEN_EZH2_TARGETS_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, KAT5_TARGET_GENES, PRKDC_TARGET_GENES, SNRNP70_TARGET_GENES, SRSF9_TARGET_GENES, ZNF184_TARGET_GENES, ZNF350_TARGET_GENES

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

GO Molecular Function (5): 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), DNA binding (GO:0003677), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	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
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

470 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF680	OR52E4	Q8NGH9	462
ZNF680	A0A1W2PQS6	A0A1W2PQS6	419
ZNF680	TRIM60	Q495X7	412
ZNF680	SPIDR	Q14159	405
ZNF680	PRKDC	P78527	387
ZNF680	POMK	Q9H5K3	386
ZNF680	HGSNAT	Q68CP4	385
ZNF680	FNTA	P49354	383
ZNF680	HOOK3	Q86VS8	379
ZNF680	DHFR	P00374	361
ZNF680	SANBR	Q6NSI8	356
ZNF680	MCM4	P33991	353
ZNF680	UBE3A	P78355	353
ZNF680	MAP1S	Q66K74	353
ZNF680	DHFR2	Q86XF0	351

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ZNF680		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): ZNF680 (Proximity Label-MS), ZNF680 (Affinity Capture-MS), ZNF680 (Proximity Label-MS), ZNF680 (Affinity Capture-MS), ZNF680 (Affinity Capture-MS), ZNF680 (Affinity Capture-MS), ZNF680 (Affinity Capture-RNA)

ESM2 similar proteins: A6NK75, A6NNF4, A6NP11, A8MTY0, A8MUV8, B4DXR9, C9JN71, O75346, O75373, O95780, P0CJ79, P0DKX0, P0DPD5, P17019, P17035, P35789, Q03923, Q03938, Q08AN1, Q14593, Q15928, Q3SXZ3, Q3ZCX4, Q5MCW4, Q5R9S5, Q5RER9, Q68DY1, Q6JLC9, Q6ZMV8, Q6ZN06, Q6ZN08, Q6ZNA1, Q76KX8, Q86T29, Q86V71, Q8IYN0, Q8N4W9, Q8N7M2, Q8NEM1, Q8TD23

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

929 predictions. Top by Δscore:

Variant	Effect	Δscore
7:64522501:C:CC	acceptor_gain	1.0000
7:64544345:T:A	donor_gain	1.0000
7:64522496:TATAA:T	acceptor_gain	0.9900
7:64522498:TAA:T	acceptor_gain	0.9900
7:64547294:C:CA	donor_gain	0.9900
7:64523307:C:CT	donor_gain	0.9800
7:64523308:T:TT	donor_gain	0.9800
7:64524708:A:C	donor_gain	0.9800
7:64543800:TACCT:T	acceptor_loss	0.9800
7:64543801:ACCTG:A	acceptor_loss	0.9800
7:64543802:CCTG:C	acceptor_loss	0.9800
7:64543803:C:CA	acceptor_loss	0.9800
7:64543804:T:A	acceptor_loss	0.9800
7:64562919:TCTCA:T	donor_loss	0.9800
7:64562920:CTCAC:C	donor_loss	0.9800
7:64562921:TCA:T	donor_loss	0.9800
7:64562922:CACC:C	donor_loss	0.9800
7:64562923:A:AG	donor_loss	0.9800
7:64562959:G:C	donor_gain	0.9800
7:64522497:ATAA:A	acceptor_gain	0.9700
7:64543701:ACCT:A	donor_loss	0.9700
7:64543702:CCTA:C	donor_loss	0.9700
7:64543704:TA:T	donor_loss	0.9700
7:64543705:A:AG	donor_loss	0.9700
7:64543706:C:CA	donor_loss	0.9700
7:64543805:G:C	acceptor_loss	0.9700
7:64544433:C:CC	acceptor_gain	0.9700
7:64544433:CTGAA:C	acceptor_loss	0.9700
7:64544434:T:G	acceptor_loss	0.9700
7:64544435:G:C	acceptor_loss	0.9700

AlphaMissense

3572 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:64521509:A:C	F415L	0.992
7:64521509:A:T	F415L	0.992
7:64521511:A:G	F415L	0.992
7:64521257:A:C	F499L	0.991
7:64521257:A:T	F499L	0.991
7:64521259:A:G	F499L	0.991
7:64521425:A:C	F443L	0.988
7:64521425:A:T	F443L	0.988
7:64521427:A:G	F443L	0.988
7:64521677:A:C	F359L	0.986
7:64521677:A:T	F359L	0.986
7:64521679:A:G	F359L	0.986
7:64521576:A:G	L393P	0.984
7:64521593:A:C	F387L	0.984
7:64521593:A:T	F387L	0.984
7:64521595:A:G	F387L	0.984
7:64521761:A:C	F331L	0.984
7:64521761:A:T	F331L	0.984
7:64521763:A:G	F331L	0.984
7:64521566:A:C	H396Q	0.983
7:64521566:A:T	H396Q	0.983
7:64521845:A:C	F303L	0.983
7:64521845:A:T	F303L	0.983
7:64521847:A:G	F303L	0.983
7:64521486:C:G	R423P	0.981
7:64521929:A:C	F275L	0.980
7:64521929:A:T	F275L	0.980
7:64521931:A:G	F275L	0.980
7:64521554:A:C	H400Q	0.978
7:64521554:A:T	H400Q	0.978

dbSNP variants (sampled 300 via entrez): RS1000003437 (7:64534038 G>A,C), RS1000051732 (7:64564538 G>C), RS1000126260 (7:64500093 C>G,T), RS1000133875 (7:64511670 T>A,C), RS1000164570 (7:64558828 G>A), RS1000183982 (7:64517138 GA>G,GAA), RS1000258248 (7:64546863 G>A,C,T), RS1000282266 (7:64509237 T>A,G), RS1000316579 (7:64545986 C>T), RS1000481619 (7:64503927 ATCT>A), RS1000500625 (7:64560809 C>A), RS1000511335 (7:64503662 G>A,T), RS1000549894 (7:64547612 T>C), RS1000568742 (7:64553885 T>C), RS1000586534 (7:64503468 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

1 associations (top):

Study	Trait	p-value
GCST009391_1122	Metabolite levels	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010523	phosphoglyceric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
polyhexamethyleneguanidine	affects expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Manganese	increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Sodium Dodecyl Sulfate	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HD39	HEK293 eGFP-ZNF680	Transformed cell line	Female

Clinical trials (associated diseases)

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