ZNF66

Summary

ZNF66 (zinc finger protein 66, HGNC:13135) is a protein-coding gene on chromosome 19p12, encoding Zinc finger protein 66 (Q6ZN08). 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 membrane and nucleus.

Source: NCBI Gene 7617 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• MANE Select transcript: NM_001355197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13135
Approved symbol	ZNF66
Name	zinc finger protein 66
Location	19p12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16537
Ensembl gene	ENSG00000160229
Ensembl biotype	protein_coding
Entrez	7617

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000344519, ENST00000360204, ENST00000594534, ENST00000913345, ENST00000913346

RefSeq mRNA: 1 — MANE Select: NM_001355197 NM_001355197

CCDS: CCDS92572

Canonical transcript exons

ENST00000344519 — 4 exons

Exon	Start	End
ENSE00001368181	20805827	20809995
ENSE00001676811	20793783	20793878
ENSE00001772920	20776304	20776450
ENSE00003512164	20792512	20792638

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 82.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4348 / max 253.7529, expressed in 1282 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174869	7.0961	1270
174870	0.3387	199

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.21	gold quality
sural nerve	UBERON:0015488	77.42	gold quality
adrenal tissue	UBERON:0018303	75.38	gold quality
ovary	UBERON:0000992	73.92	gold quality
left ovary	UBERON:0002119	73.50	gold quality
tonsil	UBERON:0002372	73.41	gold quality
islet of Langerhans	UBERON:0000006	73.39	gold quality
calcaneal tendon	UBERON:0003701	72.08	gold quality
right ovary	UBERON:0002118	71.72	gold quality
colonic epithelium	UBERON:0000397	71.60	gold quality
endometrium	UBERON:0001295	70.95	gold quality
bone marrow cell	CL:0002092	70.87	gold quality
corpus callosum	UBERON:0002336	70.71	gold quality
bone marrow	UBERON:0002371	70.48	gold quality
pancreas	UBERON:0001264	70.42	gold quality
ganglionic eminence	UBERON:0004023	70.35	gold quality
urinary bladder	UBERON:0001255	70.03	gold quality
thyroid gland	UBERON:0002046	68.78	gold quality
right lobe of thyroid gland	UBERON:0001119	68.69	gold quality
lymph node	UBERON:0000029	68.30	gold quality
ventricular zone	UBERON:0003053	68.26	gold quality
left lobe of thyroid gland	UBERON:0001120	68.25	gold quality
minor salivary gland	UBERON:0001830	68.22	gold quality
body of pancreas	UBERON:0001150	68.15	gold quality
cortical plate	UBERON:0005343	68.15	gold quality
saliva-secreting gland	UBERON:0001044	67.94	gold quality
adrenal gland	UBERON:0002369	67.82	gold quality
left adrenal gland cortex	UBERON:0035825	67.14	gold quality
skin of abdomen	UBERON:0001416	66.93	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	1358.97
E-MTAB-10018	yes	1200.32
E-GEOD-134144	yes	914.48
E-CURD-122	yes	18.56
E-MTAB-5061	yes	13.42
E-MTAB-6678	no	902.05
E-MTAB-7008	no	118.24
E-MTAB-6142	no	63.18
E-MTAB-7606	no	25.57
E-CURD-112	no	2.23
E-ANND-3	no	1.67

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2581.1	ZNF66	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605368

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099025

Paralogs (18): ZNF430 (ENSG00000118620), ZNF92 (ENSG00000146757), ZNF22 (ENSG00000165512), ZNF680 (ENSG00000173041), 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 66 — Q6ZN08 (reviewed: Q6ZN08)

All UniProt accessions (3): Q6ZN08, I3L137, M0QY27

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_001342126* (*=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 (18 total): zinc finger region 15, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZN08-F1	73.63	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 15 (showing top): chr19p12, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, HSD17B8_TARGET_GENES, PRKDC_TARGET_GENES, ZNF350_TARGET_GENES, CC2D1A_TARGET_GENES, ZNF549_TARGET_GENES, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_UP, HE_LIM_SUN_FETAL_LUNG_C4_CYCLING_T_CELL, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, PULVER_FOREY_CELLCYCLE_PEAKING_LG1, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING

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 (2): nucleus (GO:0005634), membrane (GO:0016020)

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
cellular anatomical structure	1

Protein interactions and networks

STRING

134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF66	RFX8	Q6ZV50	402
ZNF66	RBMXL1	Q96E39	350
ZNF66	MRPL1	Q9BYD6	349
ZNF66	ARL14	Q8N4G2	348
ZNF66	ANP32A	P39687	336
ZNF66	TMEM163	Q8TC26	322
ZNF66	ZBED8L	Q8TCP9	317
ZNF66	MTARC1	Q5VT66	311
ZNF66	RGS16	O15492	291
ZNF66	MTRNR2L8	P0CJ75	275
ZNF66	NINL	Q9Y2I6	273
ZNF66	MAP2K7	O14733	269
ZNF66	PIK3R3	Q92569	251
ZNF66	RHCG	Q9UBD6	251
ZNF66	FAM24B	Q8N5W8	247
ZNF66	GPR3	P46089	247

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ECE1	ZNF66	psi-mi:“MI:0915”(physical association)	0.370
KLF8		psi-mi:“MI:0914”(association)	0.350
SP1	PPP6C	psi-mi:“MI:0914”(association)	0.350
MYB	KMT2D	psi-mi:“MI:2364”(proximity)	0.270
MYC	SETD1A	psi-mi:“MI:2364”(proximity)	0.270
RREB1	RFX1	psi-mi:“MI:2364”(proximity)	0.270
TEAD1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

ESM2 similar proteins: A6NDX5, A6NK75, A6NNF4, A6NP11, B4DXR9, B7Z6K7, C9JN71, O43361, O75290, O75373, P0CJ79, P0DKX0, P17019, P17021, P17035, P17039, P35789, Q02386, Q03938, Q08AN1, Q13106, Q15928, Q3ZCX4, Q5R9F0, Q5SXM1, Q68EA5, Q6P9A1, Q6PDB4, Q6ZN06, Q6ZN08, Q6ZNG1, Q76KX8, Q86V71, Q86XN6, Q8IYB9, Q8N4W9, Q8NEP9, Q8TBZ8, Q8TC21, Q8TF32

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

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1003 predictions. Top by Δscore:

Variant	Effect	Δscore
19:20792599:G:T	donor_gain	0.9900
19:20792634:TCTTG:T	donor_loss	0.9900
19:20792635:CTTGG:C	donor_loss	0.9900
19:20792636:TTGG:T	donor_loss	0.9900
19:20792638:GGTG:G	donor_loss	0.9900
19:20792639:G:A	donor_loss	0.9900
19:20792640:T:TT	donor_loss	0.9900
19:20792641:G:GG	donor_loss	0.9900
19:20793780:CAGGT:C	acceptor_loss	0.9900
19:20793782:G:GC	acceptor_loss	0.9900
19:20793782:GGT:G	acceptor_gain	0.9900
19:20793874:CTCAG:C	donor_loss	0.9900
19:20793875:TCAGG:T	donor_loss	0.9900
19:20793877:AG:A	donor_loss	0.9900
19:20793878:GG:G	donor_loss	0.9900
19:20793879:G:GC	donor_loss	0.9900
19:20793880:T:A	donor_loss	0.9900
19:20805826:GTTTT:G	acceptor_gain	0.9900
19:20776739:G:T	donor_gain	0.9800
19:20792502:T:G	acceptor_loss	0.9800
19:20792506:TTTCA:T	acceptor_loss	0.9800
19:20792507:TTCA:T	acceptor_loss	0.9800
19:20792508:TCA:T	acceptor_loss	0.9800
19:20792509:CAGGG:C	acceptor_loss	0.9800
19:20792510:A:AG	acceptor_gain	0.9800
19:20792510:AG:A	acceptor_gain	0.9800
19:20792510:AGG:A	acceptor_gain	0.9800
19:20792511:G:GG	acceptor_gain	0.9800
19:20792511:G:T	acceptor_loss	0.9800
19:20792511:GG:G	acceptor_gain	0.9800

AlphaMissense

3833 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:20806900:T:C	F434L	0.989
19:20806902:C:A	F434L	0.989
19:20806902:C:G	F434L	0.989
19:20806984:T:C	F462L	0.985
19:20806986:T:A	F462L	0.985
19:20806986:T:G	F462L	0.985
19:20807068:T:C	F490L	0.980
19:20807070:T:A	F490L	0.980
19:20807070:T:G	F490L	0.980
19:20806396:T:C	F266L	0.975
19:20806398:T:A	F266L	0.975
19:20806398:T:G	F266L	0.975
19:20806312:T:C	F238L	0.973
19:20806314:T:A	F238L	0.973
19:20806314:T:G	F238L	0.973
19:20806991:G:C	R464P	0.971
19:20806228:T:C	F210L	0.970
19:20806230:C:A	F210L	0.970
19:20806230:C:G	F210L	0.970
19:20806564:T:C	F322L	0.970
19:20806566:C:A	F322L	0.970
19:20806566:C:G	F322L	0.970
19:20806648:T:C	F350L	0.965
19:20806650:T:A	F350L	0.965
19:20806650:T:G	F350L	0.965
19:20807003:T:C	L468P	0.961
19:20807152:T:C	F518L	0.960
19:20807154:T:A	F518L	0.960
19:20807154:T:G	F518L	0.960
19:20807236:T:C	F546L	0.952

dbSNP variants (sampled 300 via entrez): RS1000113937 (19:20801152 C>G), RS1000142488 (19:20798026 T>G), RS1000430614 (19:20808415 G>A), RS1000511906 (19:20781851 G>T), RS1000616160 (19:20804967 T>C), RS1000627318 (19:20795698 G>A), RS1000768919 (19:20809093 GATGAA>G), RS1000897287 (19:20807729 G>A), RS1000911640 (19:20787538 T>A), RS1000929742 (19:20807553 G>A,T), RS1001012970 (19:20795567 A>C), RS1001081905 (19:20799705 A>G), RS1001086135 (19:20793214 C>T), RS1001149028 (19:20796639 T>C,G), RS1001337600 (19:20802375 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

1 associations (top):

Study	Trait	p-value
GCST003542_60	Night sleep phenotypes	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenite	increases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Niclosamide	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vanadates	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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