ZNF669

Summary

ZNF669 (zinc finger protein 669, HGNC:25736) is a protein-coding gene on chromosome 1q44, encoding Zinc finger protein 669 (Q96BR6). 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 79862 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_001142572

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25736
Approved symbol	ZNF669
Name	zinc finger protein 669
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12606
Ensembl gene	ENSG00000188295
Ensembl biotype	protein_coding
Entrez	79862

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000343381, ENST00000366500, ENST00000366501, ENST00000448299, ENST00000476158

RefSeq mRNA: 2 — MANE Select: NM_001142572 NM_001142572, NM_024804

CCDS: CCDS31088, CCDS44345

Canonical transcript exons

ENST00000448299 — 4 exons

Exon	Start	End
ENSE00001908984	247104197	247104356
ENSE00002357147	247101987	247102113
ENSE00003494491	247101731	247101791
ENSE00003576091	247099962	247101319

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 87.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9145 / max 74.8246, expressed in 1743 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18500	8.9145	1743

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	87.10	silver quality
cortical plate	UBERON:0005343	86.44	gold quality
cerebellar vermis	UBERON:0004720	86.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.36	gold quality
ganglionic eminence	UBERON:0004023	83.12	gold quality
type B pancreatic cell	CL:0000169	82.05	silver quality
nipple	UBERON:0002030	81.40	gold quality
superior surface of tongue	UBERON:0007371	81.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.34	gold quality
diaphragm	UBERON:0001103	80.04	silver quality
thymus	UBERON:0002370	79.97	gold quality
renal medulla	UBERON:0000362	79.60	gold quality
inferior vagus X ganglion	UBERON:0005363	79.27	gold quality
tongue squamous epithelium	UBERON:0006919	78.99	gold quality
dorsal plus ventral thalamus	UBERON:0001897	78.94	gold quality
subthalamic nucleus	UBERON:0001906	78.75	gold quality
ventricular zone	UBERON:0003053	78.68	gold quality
islet of Langerhans	UBERON:0000006	78.66	gold quality
ventral tegmental area	UBERON:0002691	78.54	gold quality
trachea	UBERON:0003126	78.06	gold quality
cardia of stomach	UBERON:0001162	77.96	gold quality
calcaneal tendon	UBERON:0003701	77.81	gold quality
tongue	UBERON:0001723	77.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	77.64	gold quality
superior vestibular nucleus	UBERON:0007227	77.56	gold quality
mucosa of paranasal sinus	UBERON:0005030	77.53	silver quality
male germ cell	CL:0000015	77.41	silver quality
stromal cell of endometrium	CL:0002255	77.29	gold quality
pons	UBERON:0000988	77.02	gold quality
leukocyte	CL:0000738	76.99	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: yes

JASPAR motifs

Motif	Name	Family
MA1985.1	ZNF669	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:27852650

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

10 targeting ZNF669, 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-6778-3P	99.96	67.29	2693
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-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6879-3P	93.93	64.00	759

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp78	ENSMUSG00000055150
rattus_norvegicus		ENSRNOG00000083797
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), ZNF404 (ENSG00000176222), ZNF491 (ENSG00000177599), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF875 (ENSG00000181666), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300)

Protein

Protein identifiers

Zinc finger protein 669 — Q96BR6 (reviewed: Q96BR6)

All UniProt accessions (4): E5RI66, Q96BR6, Q5VT36, Q5VT37

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?
Q96BR6-1	1	yes
Q96BR6-2	2

RefSeq proteins (2): NP_001136044, NP_079080 (=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

UniProt features (16 total): zinc finger region 9, sequence variant 2, sequence conflict 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BR6-F1	65.82	0.21

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: 58 (showing top): chr1q44, STEIN_ESRRA_TARGETS_UP, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MARTENS_TRETINOIN_RESPONSE_DN, REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, OISHI_CHOLANGIOMA_STEM_CELL_LIKE_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CBX5_TARGET_GENES, CEBPZ_TARGET_GENES, GREB1_TARGET_GENES, HDAC4_TARGET_GENES, LHX9_TARGET_GENES, NFE2L1_TARGET_GENES, PITX1_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)

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	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

522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF669	NPIPB6	E9PJ23	447
ZNF669	USP19	O94966	433
ZNF669	TBC1D3G	Q6DHY5	432
ZNF669	ANKRD34A	Q69YU3	418
ZNF669	DCHS2	Q6V1P9	412
ZNF669	DRC4	O95995	398
ZNF669	MYO3A	Q8NEV4	389
ZNF669	MAPK7	Q13164	353
ZNF669	ARID1B	Q8NFD5	353
ZNF669	EEF1AKMT2	Q5JPI9	349
ZNF669	DNAJB12	Q9NXW2	348
ZNF669	RBM19	Q9Y4C8	343
ZNF669	RSBN1	Q5VWQ0	329
ZNF669	TBC1D3H	P0C7X1	306
ZNF669	DCHS1	Q96JQ0	298

IntAct

78 interactions, top by confidence:

A	B	Type	Score
ARMC7	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
BICD2	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
CEP70	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
ZNF669	MDFI	psi-mi:“MI:0915”(physical association)	0.560
ZNF669	ZC4H2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
CDR2L	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
KRT27	ZNF669	psi-mi:“MI:0915”(physical association)	0.560
ZNF669	MID2	psi-mi:“MI:0915”(physical association)	0.560
ZNF669	PNMA2	psi-mi:“MI:0915”(physical association)	0.560
ZNF669	ZNF330	psi-mi:“MI:0915”(physical association)	0.560
ZNF669	CABP5	psi-mi:“MI:0915”(physical association)	0.560
ZNF669	ARMC7	psi-mi:“MI:0915”(physical association)	0.560
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF669	LRP4	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF669	E2	psi-mi:“MI:0915”(physical association)	0.370
ECE1	ZNF669	psi-mi:“MI:0915”(physical association)	0.370
EFEMP1	ZNF316	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): ZNF669 (Affinity Capture-MS), FBXW8 (Affinity Capture-MS), ANKS3 (Affinity Capture-MS), CUL7 (Affinity Capture-MS), SESTD1 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), MTMR4 (Affinity Capture-MS), TRIM41 (Affinity Capture-MS), ZNF669 (Affinity Capture-MS), TRIM39 (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), USP34 (Affinity Capture-MS), LTBP4 (Affinity Capture-MS), SMARCAD1 (Affinity Capture-MS), NEK7 (Affinity Capture-MS)

ESM2 similar proteins: A0JPL0, A1L1L7, A2A761, A2T7D2, A3KN36, A7MBI1, A8MT65, B2RXC5, G3X9G7, P08042, P0CG31, P17023, P18728, P21506, P52738, Q02525, Q12901, Q2VY69, Q49AA0, Q4R6J4, Q4V8A8, Q571J5, Q5FWF6, Q5JNZ3, Q5RB33, Q5REF1, Q5T5D7, Q5VIY5, Q61967, Q6ZN11, Q6ZNG0, Q86XU0, Q8BGV5, Q8N782, Q8N859, Q8N9Z0, Q8R1D1, Q8TF39, Q96BR6, Q96N20

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

294 predictions. Top by Δscore:

Variant	Effect	Δscore
1:247101315:GATTT:G	acceptor_gain	1.0000
1:247101316:ATTT:A	acceptor_gain	1.0000
1:247101317:TTT:T	acceptor_gain	1.0000
1:247101317:TTTC:T	acceptor_loss	1.0000
1:247101318:TT:T	acceptor_gain	1.0000
1:247101318:TTCT:T	acceptor_loss	1.0000
1:247101320:C:CC	acceptor_gain	1.0000
1:247101322:G:C	acceptor_gain	1.0000
1:247101330:A:AC	acceptor_gain	1.0000
1:247101726:ATTAC:A	donor_loss	1.0000
1:247101727:TTACC:T	donor_loss	1.0000
1:247101728:TAC:T	donor_loss	1.0000
1:247101729:ACCTT:A	donor_loss	1.0000
1:247101730:CC:C	donor_loss	1.0000
1:247101983:TTA:T	donor_loss	1.0000
1:247101985:A:AC	donor_gain	1.0000
1:247101985:A:AT	donor_loss	1.0000
1:247101986:C:CC	donor_gain	1.0000
1:247101986:CCTA:C	donor_gain	1.0000
1:247102112:TC:T	acceptor_gain	1.0000
1:247102112:TCCT:T	acceptor_loss	1.0000
1:247102113:CC:C	acceptor_gain	1.0000
1:247102120:C:CT	acceptor_gain	1.0000
1:247102125:C:CT	acceptor_gain	1.0000
1:247102125:C:T	acceptor_gain	1.0000
1:247102127:CACA:C	acceptor_gain	1.0000
1:247102129:CA:C	acceptor_gain	1.0000
1:247102130:A:AC	acceptor_gain	1.0000
1:247102130:A:C	acceptor_gain	1.0000
1:247101322:G:GC	acceptor_gain	0.9900

AlphaMissense

2523 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:247100572:G:C	F399L	0.996
1:247100572:G:T	F399L	0.996
1:247100574:A:G	F399L	0.996
1:247100656:A:C	F371L	0.995
1:247100656:A:T	F371L	0.995
1:247100658:A:G	F371L	0.995
1:247100740:G:C	F343L	0.994
1:247100740:G:T	F343L	0.994
1:247100742:A:G	F343L	0.994
1:247100908:G:C	F287L	0.992
1:247100908:G:T	F287L	0.992
1:247100910:A:G	F287L	0.992
1:247102079:A:G	F99S	0.991
1:247100953:G:C	H272Q	0.989
1:247100953:G:T	H272Q	0.989
1:247102078:A:C	F99L	0.988
1:247102078:A:T	F99L	0.988
1:247102080:A:G	F99L	0.988
1:247100483:C:G	R429P	0.986
1:247100533:A:C	H412Q	0.986
1:247100533:A:T	H412Q	0.986
1:247100701:A:C	H356Q	0.986
1:247100701:A:T	H356Q	0.986
1:247100876:C:G	R298P	0.985
1:247100992:A:C	F259L	0.984
1:247100992:A:T	F259L	0.984
1:247100994:A:G	F259L	0.984
1:247100869:G:C	H300Q	0.983
1:247100869:G:T	H300Q	0.983
1:247100629:A:C	H380Q	0.982

dbSNP variants (sampled 300 via entrez): RS1000921480 (1:247104544 C>A,T), RS1001066025 (1:247105581 G>A), RS1001920160 (1:247105784 T>C), RS1001975491 (1:247105570 T>A), RS1002067517 (1:247100264 G>A,C,T), RS1002766174 (1:247103225 C>A), RS1003228054 (1:247102831 C>A,T), RS1003253971 (1:247105856 TAA>T,TAAA), RS1003732572 (1:247101421 T>C), RS1004170977 (1:247102792 G>A,T), RS1004219575 (1:247101006 A>C,G), RS1004507498 (1:247101240 C>G,T), RS1006063706 (1:247102472 C>A), RS1006729047 (1:247104838 C>G), RS1007511614 (1:247105081 G>A,C)

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

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Tobacco Smoke Pollution	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases 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
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Polycyclic Aromatic Hydrocarbons	decreases expression, increases abundance, affects cotreatment	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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