ZFP69

Summary

ZFP69 (ZFP69 zinc finger protein, HGNC:24708) is a protein-coding gene on chromosome 1p34.2, encoding Zinc finger protein 69 homolog (Q49AA0). Putative transcription factor that appears to regulate lipid metabolism. It is a selective cancer dependency (DepMap: 10.2% of cell lines).

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 lipid metabolic process and regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 339559 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total
• Cancer dependency (DepMap): dependent in 10.2% of screened cell lines
• MANE Select transcript: NM_001320179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24708
Approved symbol	ZFP69
Name	ZFP69 zinc finger protein
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	ZKSCAN23A, FLJ16030, ZFP69A, ZSCAN54A
Ensembl gene	ENSG00000187815
Ensembl biotype	protein_coding
OMIM	617939
Entrez	339559

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000372705, ENST00000372706, ENST00000482712, ENST00000853134, ENST00000853135, ENST00000853136, ENST00000853137, ENST00000853138, ENST00000853139, ENST00000853140, ENST00000953011, ENST00000953012, ENST00000953013, ENST00000953014, ENST00000953015

RefSeq mRNA: 3 — MANE Select: NM_001320179 NM_001320178, NM_001320179, NM_198494

CCDS: CCDS30686

Canonical transcript exons

ENST00000372706 — 6 exons

Exon	Start	End
ENSE00001191504	40481763	40481854
ENSE00001458432	40494921	40496343
ENSE00001458433	40479036	40479488
ENSE00001458434	40477290	40477894
ENSE00001637850	40489088	40489214
ENSE00003681439	40489529	40489624

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 87.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.9778 / max 79.4328, expressed in 1065 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2389	1.9778	1065

Top tissues by expression

232 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	87.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.10	gold quality
cortical plate	UBERON:0005343	80.93	gold quality
ganglionic eminence	UBERON:0004023	77.83	gold quality
oocyte	CL:0000023	77.45	gold quality
ventricular zone	UBERON:0003053	76.51	gold quality
granulocyte	CL:0000094	76.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.20	gold quality
calcaneal tendon	UBERON:0003701	75.12	gold quality
leukocyte	CL:0000738	74.91	gold quality
monocyte	CL:0000576	74.76	gold quality
smooth muscle tissue	UBERON:0001135	74.08	gold quality
stromal cell of endometrium	CL:0002255	73.66	gold quality
descending thoracic aorta	UBERON:0002345	73.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	73.15	gold quality
body of uterus	UBERON:0009853	72.90	gold quality
right uterine tube	UBERON:0001302	72.73	gold quality
apex of heart	UBERON:0002098	72.65	gold quality
secondary oocyte	CL:0000655	72.58	gold quality
left coronary artery	UBERON:0001626	72.57	gold quality
lower esophagus	UBERON:0013473	72.52	gold quality
thoracic aorta	UBERON:0001515	72.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	72.50	gold quality
metanephros cortex	UBERON:0010533	72.48	gold quality
ascending aorta	UBERON:0001496	72.41	gold quality
right coronary artery	UBERON:0001625	72.33	gold quality
spleen	UBERON:0002106	72.11	gold quality
aorta	UBERON:0000947	72.03	gold quality
spinal cord	UBERON:0002240	72.03	gold quality
popliteal artery	UBERON:0002250	71.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting ZFP69, 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-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-6838-3P	98.40	65.88	559
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-4715-5P	97.62	67.47	506

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Zfp69 is the most likely candidate for the diabetogenic effect of Nidd/SJL locus. (PMID:19578398)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp69	ENSMUSG00000064141
rattus_norvegicus	Zfp69	ENSRNOG00000028662
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 69 homolog — Q49AA0 (reviewed: Q49AA0)

Alternative names: Zinc finger protein 642

All UniProt accessions (1): Q49AA0

UniProt curated annotations — full annotation on UniProt →

Function. Putative transcription factor that appears to regulate lipid metabolism.

Subcellular location. Nucleus.

Tissue specificity. Expressed in visceral and subcutaneous adipose tissue.

Induction. Up-regulated in both visceral and subcutaneous adipose tissue of diabetic individuals.

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

RefSeq proteins (3): NP_001307107, NP_001307108, NP_940896 (=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 (14 total): zinc finger region 9, domain 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q49AA0-F1	65.53	0.05

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 57 (showing top): GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, chr1p34, GOBP_LIPID_METABOLIC_PROCESS, AGCATTA_MIR155, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, HATADA_METHYLATED_IN_LUNG_CANCER_UP, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_129_MOUSE_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GSE14415_INDUCED_TREG_VS_FOXP3_KO_INDUCED_TREG_IL2_CULTURE_UP, RLF_TARGET_GENES, ZFP91_TARGET_GENES, ZNF274_TARGET_GENES, MIR335_3P, MIR5696, MIR4668_5P

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), lipid metabolic process (GO:0006629), regulation of lipid metabolic process (GO:0019216), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): 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), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nuclear lumen (GO:0031981)

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
primary metabolic process	1
lipid metabolic process	1
regulation of primary metabolic process	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
cation binding	1
intracellular membrane-bounded organelle	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFP69	ZDHHC23	Q8IYP9	657
ZFP69	TBC1D1	Q86TI0	620
ZFP69	SORCS1	Q8WY21	595
ZFP69	ILDR2	Q71H61	506
ZFP69	TMCO2	Q7Z6W1	476
ZFP69	SMAP2	Q8WU79	446
ZFP69	PCTP	Q9UKL6	400
ZFP69	MANSC1	Q9H8J5	383
ZFP69	PDCL2	Q8N4E4	360
ZFP69	NUGGC	Q68CJ6	356
ZFP69	NMUR2	Q9GZQ4	330
ZFP69	AUNIP	Q9H7T9	324
ZFP69	BTBD8	Q5XKL5	323
ZFP69	TMEM54	Q969K7	321
ZFP69	TOX4	O94842	318

IntAct

0 interactions, top by confidence:

BioGRID (2): ZFP69 (Affinity Capture-RNA), ZFP69 (Co-fractionation)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1109 predictions. Top by Δscore:

Variant	Effect	Δscore
1:40481761:A:AG	acceptor_gain	1.0000
1:40481762:G:GA	acceptor_gain	1.0000
1:40481762:GC:G	acceptor_gain	1.0000
1:40481762:GCT:G	acceptor_gain	1.0000
1:40481762:GCTC:G	acceptor_gain	1.0000
1:40481762:GCTCT:G	acceptor_gain	1.0000
1:40481850:CCCAG:C	donor_gain	1.0000
1:40481851:CCAG:C	donor_gain	1.0000
1:40481852:CAG:C	donor_gain	1.0000
1:40481852:CAGG:C	donor_loss	1.0000
1:40481853:AG:A	donor_gain	1.0000
1:40481854:GG:G	donor_gain	1.0000
1:40481854:GGT:G	donor_loss	1.0000
1:40481855:G:GG	donor_gain	1.0000
1:40489211:GTGG:G	donor_gain	1.0000
1:40477892:GTG:G	donor_gain	0.9900
1:40477893:TGG:T	donor_loss	0.9900
1:40477895:G:GG	donor_gain	0.9900
1:40477895:GT:G	donor_loss	0.9900
1:40477896:T:TC	donor_loss	0.9900
1:40477897:G:GG	donor_loss	0.9900
1:40481757:CCCCA:C	acceptor_gain	0.9900
1:40481758:CCCA:C	acceptor_gain	0.9900
1:40481759:CCAG:C	acceptor_gain	0.9900
1:40481760:CA:C	acceptor_gain	0.9900
1:40481761:A:AT	acceptor_gain	0.9900
1:40481762:G:T	acceptor_gain	0.9900
1:40489207:GTC:G	donor_gain	0.9900
1:40489213:GG:G	donor_gain	0.9900
1:40489214:GG:G	donor_gain	0.9900

AlphaMissense

3524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:40495484:T:C	F336L	1.000
1:40495486:C:A	F336L	1.000
1:40495486:C:G	F336L	1.000
1:40495568:T:C	F364L	1.000
1:40495570:C:A	F364L	1.000
1:40495570:C:G	F364L	1.000
1:40495400:T:C	F308L	0.999
1:40495402:T:A	F308L	0.999
1:40495402:T:G	F308L	0.999
1:40495597:T:A	H373Q	0.999
1:40495597:T:G	H373Q	0.999
1:40495736:T:C	F420L	0.999
1:40495738:T:A	F420L	0.999
1:40495738:T:G	F420L	0.999
1:40495820:T:C	F448L	0.999
1:40495822:T:A	F448L	0.999
1:40495822:T:G	F448L	0.999
1:40495988:T:C	F504L	0.999
1:40495990:C:A	F504L	0.999
1:40495990:C:G	F504L	0.999
1:40495419:T:C	L314P	0.998
1:40495485:T:C	F336S	0.998
1:40495503:T:C	L342P	0.998
1:40495511:C:G	H345D	0.998
1:40495513:T:A	H345Q	0.998
1:40495513:T:G	H345Q	0.998
1:40495525:C:A	H349Q	0.998
1:40495525:C:G	H349Q	0.998
1:40495569:T:C	F364S	0.998
1:40495595:C:G	H373D	0.998

dbSNP variants (sampled 300 via entrez): RS1000119744 (1:40490971 G>A), RS1000602900 (1:40475797 G>A), RS1000988784 (1:40475398 C>A,G,T), RS1001054163 (1:40493049 A>C,G), RS1001513992 (1:40481977 C>G), RS1001545307 (1:40476713 T>C), RS1001606402 (1:40491845 C>G), RS1001616293 (1:40483305 T>C), RS1001959712 (1:40483508 C>G,T), RS1002293355 (1:40480832 T>A), RS1002337684 (1:40481403 T>C), RS1002401863 (1:40487090 AATTTTTGT>A), RS1002742096 (1:40486819 T>G), RS1002752405 (1:40480542 C>T), RS1003023674 (1:40493255 G>A)

Disease associations

OMIM: gene MIM:617939 | 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

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
Valproic Acid	decreases methylation, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
arsenite	increases methylation	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Formaldehyde	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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