ZNF69

Summary

ZNF69 (zinc finger protein 69, HGNC:13138) is a protein-coding gene on chromosome 19p13.2, encoding Zinc finger protein 69 (Q9UC07). May be involved in transcriptional regulation.

Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 7620 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 229 total
• MANE Select transcript: NM_001364730

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13138
Approved symbol	ZNF69
Name	zinc finger protein 69
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Cos5
Ensembl gene	ENSG00000198429
Ensembl biotype	protein_coding
OMIM	194543
Entrez	7620

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000340180, ENST00000429654, ENST00000445911, ENST00000885309, ENST00000912670

RefSeq mRNA: 4 — MANE Select: NM_001364730 NM_001321163, NM_001364730, NM_001364731, NM_021915

CCDS: CCDS32914, CCDS92521

Canonical transcript exons

ENST00000429654 — 4 exons

Exon	Start	End
ENSE00001748044	11903905	11903965
ENSE00001776408	11903573	11903699
ENSE00001797108	11904649	11906696
ENSE00001953440	11887782	11887986

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 80.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8041 / max 146.3959, expressed in 1200 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173970	4.8041	1200

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	80.33	gold quality
metanephros cortex	UBERON:0010533	80.27	gold quality
ventricular zone	UBERON:0003053	79.86	gold quality
rectum	UBERON:0001052	78.85	gold quality
mucosa of transverse colon	UBERON:0004991	78.35	gold quality
ganglionic eminence	UBERON:0004023	78.23	gold quality
right uterine tube	UBERON:0001302	78.19	gold quality
cortex of kidney	UBERON:0001225	77.98	gold quality
kidney	UBERON:0002113	77.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.26	gold quality
cortical plate	UBERON:0005343	77.17	gold quality
adult mammalian kidney	UBERON:0000082	76.78	gold quality
right lobe of liver	UBERON:0001114	76.47	gold quality
body of pancreas	UBERON:0001150	76.41	gold quality
stomach	UBERON:0000945	76.37	gold quality
body of stomach	UBERON:0001161	76.22	gold quality
liver	UBERON:0002107	76.14	gold quality
pancreas	UBERON:0001264	75.91	gold quality
transverse colon	UBERON:0001157	75.67	gold quality
adrenal tissue	UBERON:0018303	75.33	gold quality
islet of Langerhans	UBERON:0000006	75.21	gold quality
stromal cell of endometrium	CL:0002255	75.20	gold quality
fundus of stomach	UBERON:0001160	75.20	gold quality
ovary	UBERON:0000992	74.87	gold quality
endometrium	UBERON:0001295	74.63	gold quality
right adrenal gland	UBERON:0001233	74.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.52	gold quality
left ovary	UBERON:0002119	74.48	gold quality
adrenal gland	UBERON:0002369	74.30	gold quality
right ovary	UBERON:0002118	74.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting ZNF69, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-3926	98.95	69.26	1438

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 69 — Q9UC07 (reviewed: Q9UC07)

Alternative names: hZNF3

All UniProt accessions (2): C9JR48, Q9UC07

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?
Q9UC07-1	1	yes
Q9UC07-2	2

RefSeq proteins (4): NP_001308092, NP_001351659, NP_001351660, NP_068734 (=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, PF13894

UniProt features (18 total): zinc finger region 14, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UC07-F1	69.80	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): chr19p13, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR3910, MIR3123, MIR1303, MIR3926, MIR6829_3P, MIR6791_3P, MIR1911_3P, JINESH_BLEBBISHIELD_VS_LIVE_CONTROL_UP, JINESH_BLEBBISHIELD_TRANSFORMED_STEM_CELL_SPHERES_DN, BDP1_TARGET_GENES, QI_PBMC_ZOSTAVAX_AGE_50_75YO_CORRELATED_WITH_CONTRACTION_OF_VZV_SPECIFIC_T_CELLS_PEAK_TO_28DYAT_1DY_NEGATIVE, OSMAN_BLOOD_CHAD63_KH_AGE_18_50YO_HIGH_DOSE_SUBJECTS_24HR_DN

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

GO Molecular Function (7): 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), identical protein binding (GO:0042802), 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
protein binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF69	CRBN	Q96SW2	516
ZNF69	RNF166	Q96A37	435
ZNF69	GSPT1	P15170	393
ZNF69	CENPA	P49450	381
ZNF69	ZNF827	Q17R98	381
ZNF69	ZNF276	Q8N554	370
ZNF69	DTWD1	Q8N5C7	367
ZNF69	IQCC	Q4KMZ1	354
ZNF69	IQCF6	A8MYZ5	327
ZNF69	PGBD2	Q6P3X8	324
ZNF69	SACK1F	Q8NEG4	321
ZNF69	EXO5	Q9H790	311
ZNF69	TDRD15	B5MCY1	308
ZNF69	ACTMAP	Q5BKX5	306
ZNF69	KRTAP4-5	Q9BYR2	287
ZNF69	ILF3	Q12906	287

IntAct

10 interactions, top by confidence:

A	B	Type	Score
KRT31	ZNF69	psi-mi:“MI:0915”(physical association)	0.560
ZNF69	KATNAL1	psi-mi:“MI:0915”(physical association)	0.560
ZNF69	KRT31	psi-mi:“MI:0915”(physical association)	0.560
ZNF69	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
ZNF69	CFTR	psi-mi:“MI:0915”(physical association)	0.370
ZNF69	ZNF763	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): ZNF69 (Two-hybrid), KATNAL1 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Two-hybrid), ZNF69 (Proximity Label-MS)

ESM2 similar proteins: A0A1W2PQL4, A0JPL0, A2RRD8, A6NHJ4, A6NP11, B4DX44, O75346, O95780, P0CB33, P21506, P51508, P52738, Q0D2J5, Q0VGE8, Q12901, Q13360, Q14593, Q15973, Q2M218, Q2M3X9, Q2VY69, Q3SXZ3, Q5HY98, Q5RCJ2, Q5VIY5, Q6J6I6, Q7L2R6, Q86XU0, Q86Y25, Q8IW36, Q8IYN0, Q8IYX0, Q8N782, Q8N883, Q8N9Z0, Q8NDP4, Q95K49, Q969W8, Q96H40, Q96N58

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	198
Likely benign	20
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

696 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11904639:T:G	acceptor_gain	1.0000
19:11904647:A:AG	acceptor_gain	1.0000
19:11904647:A:C	acceptor_loss	1.0000
19:11904647:AG:A	acceptor_gain	1.0000
19:11904648:G:GA	acceptor_gain	1.0000
19:11904648:GG:G	acceptor_gain	1.0000
19:11904648:GGA:G	acceptor_gain	1.0000
19:11904648:GGAGT:G	acceptor_gain	1.0000
19:11887981:G:GT	donor_gain	0.9900
19:11903556:C:G	acceptor_gain	0.9900
19:11903557:AT:A	acceptor_gain	0.9900
19:11903557:ATGT:A	acceptor_gain	0.9900
19:11903558:T:G	acceptor_gain	0.9900
19:11903696:GTAG:G	donor_gain	0.9900
19:11904638:A:AG	acceptor_gain	0.9900
19:11904643:T:A	acceptor_gain	0.9900
19:11887944:G:GT	donor_gain	0.9800
19:11887982:A:T	donor_gain	0.9800
19:11902411:G:GA	donor_gain	0.9800
19:11903555:A:AG	acceptor_gain	0.9800
19:11903555:ACAT:A	acceptor_gain	0.9800
19:11903695:TGTAG:T	donor_loss	0.9800
19:11903697:TAGG:T	donor_loss	0.9800
19:11903698:AGGT:A	donor_loss	0.9800
19:11903699:GGT:G	donor_loss	0.9800
19:11903700:G:A	donor_loss	0.9800
19:11903701:T:G	donor_loss	0.9800
19:11903961:TTCAG:T	donor_loss	0.9800
19:11903962:TCAG:T	donor_loss	0.9800
19:11903963:CAGG:C	donor_loss	0.9800

AlphaMissense

3795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11905670:T:C	F425L	0.991
19:11905672:C:A	F425L	0.991
19:11905672:C:G	F425L	0.991
19:11905166:T:C	F257L	0.989
19:11905168:T:A	F257L	0.989
19:11905168:T:G	F257L	0.989
19:11905586:T:C	F397L	0.988
19:11905588:C:A	F397L	0.988
19:11905588:C:G	F397L	0.988
19:11905754:T:C	F453L	0.988
19:11905756:C:A	F453L	0.988
19:11905756:C:G	F453L	0.988
19:11905250:T:C	F285L	0.987
19:11905252:T:A	F285L	0.987
19:11905252:T:G	F285L	0.987
19:11905856:T:C	F487L	0.986
19:11905858:T:A	F487L	0.986
19:11905858:T:G	F487L	0.986
19:11903607:T:C	F33S	0.984
19:11905760:T:C	S455P	0.983
19:11906024:T:C	F543L	0.982
19:11906026:C:A	F543L	0.982
19:11906026:C:G	F543L	0.982
19:11905502:T:C	F369L	0.981
19:11905504:T:A	F369L	0.981
19:11905504:T:G	F369L	0.981
19:11903606:T:C	F33L	0.980
19:11903608:C:A	F33L	0.980
19:11903608:C:G	F33L	0.980
19:11905082:T:C	F229L	0.979

dbSNP variants (sampled 300 via entrez): RS1000031080 (19:11974612 C>G,T), RS1000057418 (19:11945987 G>C), RS1000102796 (19:11954652 G>A,C,T), RS1000118339 (19:11941121 G>A), RS1000307814 (19:11963343 C>G,T), RS1000347838 (19:11957233 A>G), RS1000354256 (19:11918393 G>A,C), RS1000355618 (19:11919187 G>A,T), RS1000362983 (19:11907370 T>C), RS1000366956 (19:11957490 TA>T), RS1000386731 (19:11919010 C>G), RS1000430019 (19:11945837 G>C), RS1000536597 (19:11923777 G>A,C), RS1000541068 (19:11941326 C>A), RS1000551024 (19:11899643 A>T)

Disease associations

OMIM: gene MIM:194543 | 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
GCST90002390_523	Mean corpuscular hemoglobin	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

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
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
erucylphospho-N,N,N-trimethylpropylammonium	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	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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