ZNF565

Summary

ZNF565 (zinc finger protein 565, HGNC:26726) is a protein-coding gene on chromosome 19q13.12, encoding Zinc finger protein 565 (Q8N9K5). 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 transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 147929 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_152477

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26726
Approved symbol	ZNF565
Name	zinc finger protein 565
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36991
Ensembl gene	ENSG00000196357
Ensembl biotype	protein_coding
OMIM	614275
Entrez	147929

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 retained_intron

ENST00000304116, ENST00000355114, ENST00000392173, ENST00000585994, ENST00000586648, ENST00000587803, ENST00000591473, ENST00000877508, ENST00000877509, ENST00000877510, ENST00000920739, ENST00000920740, ENST00000920741, ENST00000964655, ENST00000964656

RefSeq mRNA: 5 — MANE Select: NM_152477 NM_001042474, NM_001366188, NM_001366189, NM_001366190, NM_152477

CCDS: CCDS12491

Canonical transcript exons

ENST00000304116 — 5 exons

Exon	Start	End
ENSE00001145359	36182276	36183733
ENSE00001510953	36214622	36214665
ENSE00003490460	36194233	36194328
ENSE00003519078	36195030	36195156
ENSE00003684808	36201977	36202050

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 88.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.1900 / max 57.4145, expressed in 1034 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180662	2.0956	1023
180663	0.0792	28
180665	0.0152	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	88.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.06	gold quality
medial globus pallidus	UBERON:0002477	82.87	gold quality
globus pallidus	UBERON:0001875	80.45	gold quality
corpus callosum	UBERON:0002336	80.19	gold quality
cartilage tissue	UBERON:0002418	79.14	gold quality
sperm	CL:0000019	78.34	gold quality
postcentral gyrus	UBERON:0002581	78.20	gold quality
secondary oocyte	CL:0000655	77.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.75	gold quality
cortical plate	UBERON:0005343	77.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	76.87	gold quality
inferior vagus X ganglion	UBERON:0005363	76.63	gold quality
parietal lobe	UBERON:0001872	76.59	gold quality
ventricular zone	UBERON:0003053	76.14	gold quality
tendon	UBERON:0000043	76.07	gold quality
stromal cell of endometrium	CL:0002255	75.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.48	gold quality
ganglionic eminence	UBERON:0004023	75.12	gold quality
embryo	UBERON:0000922	75.11	gold quality
calcaneal tendon	UBERON:0003701	75.01	gold quality
deltoid	UBERON:0001476	74.76	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	74.60	gold quality
islet of Langerhans	UBERON:0000006	74.35	gold quality
spinal cord	UBERON:0002240	74.26	gold quality
muscle of leg	UBERON:0001383	74.13	gold quality
tendon of biceps brachii	UBERON:0008188	73.98	silver quality
entorhinal cortex	UBERON:0002728	73.81	gold quality
gastrocnemius	UBERON:0001388	73.77	gold quality
oviduct epithelium	UBERON:0004804	73.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting ZNF565, 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-188-3P	100.00	68.76	1240
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-188-5P	97.89	67.01	756
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-6866-3P	97.38	66.94	748

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger protein 565 — Q8N9K5 (reviewed: Q8N9K5)

All UniProt accessions (3): Q8N9K5, K7EL42, K7ESE2

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?
Q8N9K5-1	1	yes
Q8N9K5-2	2

RefSeq proteins (5): NP_001035939, NP_001353117, NP_001353118, NP_001353119, NP_689690* (*=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 (16 total): zinc finger region 12, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9K5-F1	73.38	0.33

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 105 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, E2F_Q4, GCM_MAP4K4, E2F_Q4_01, GCM_PTPRD, TGCGCANK_UNKNOWN, E2F4DP1_01, E2F1DP1_01, E2F_Q3, E2F1DP2_01, MYCMAX_01, E2F1_Q3, E2F_Q6_01, GCM_PTK2, E2F_Q3_01

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 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), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (1): nucleus (GO:0005634)

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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
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
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
double-stranded DNA binding	1
sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF565	ZFR	Q96KR1	370
ZNF565	MTFR2	Q6P444	359
ZNF565	TACC1	O75410	348
ZNF565	TCAF2	A6NFQ2	348
ZNF565	ZBTB3	Q9H5J0	348
ZNF565	TMC4	Q7Z404	324
ZNF565	TM9SF3	Q9HD45	323
ZNF565	GPR153	Q6NV75	319
ZNF565	DDX28	Q9NUL7	314
ZNF565	IVNS1ABP	Q9Y6Y0	313
ZNF565	FEM1C	Q96JP0	310
ZNF565	GPRIN1	Q7Z2K8	306
ZNF565	GPCPD1	Q9NPB8	305
ZNF565	PELO	Q9BRX2	300
ZNF565	BLZF1	Q9H2G9	300

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ZNF565	IPO8	psi-mi:“MI:0914”(association)	0.350
APP	ZNF565	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): ZNF565 (Proximity Label-MS), ZNF565 (Affinity Capture-MS), ZNF565 (Two-hybrid), ZNF565 (Affinity Capture-RNA)

ESM2 similar proteins: A3KN32, A3KN36, O14709, O43296, O75123, P15622, P16373, P17023, P17031, P17097, P52736, P85977, Q07230, Q12901, Q14929, Q29RZ4, Q4V8A8, Q571J5, Q5CZA5, Q5JNZ3, Q5R7I8, Q5RBX0, Q5RBY9, Q5RCD9, Q5RCX4, Q61751, Q61967, Q6GQR8, Q6IV72, Q6NX45, Q6PK81, Q6ZMS4, Q7TNU6, Q7TSH9, Q7Z398, Q7Z7L9, Q8BI99, Q8BIQ3, Q8BLB0, Q8IZ26

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1440 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36183729:CAAGT:C	acceptor_gain	1.0000
19:36183734:C:CC	acceptor_gain	1.0000
19:36194227:GCTTA:G	donor_loss	1.0000
19:36194228:CTTAC:C	donor_loss	1.0000
19:36194229:TTA:T	donor_loss	1.0000
19:36194230:TACCT:T	donor_loss	1.0000
19:36194231:A:C	donor_loss	1.0000
19:36194232:C:CA	donor_loss	1.0000
19:36194326:GTC:G	acceptor_gain	1.0000
19:36194327:TC:T	acceptor_gain	1.0000
19:36194328:CC:C	acceptor_gain	1.0000
19:36194329:C:CC	acceptor_gain	1.0000
19:36194329:CT:C	acceptor_loss	1.0000
19:36194330:T:A	acceptor_loss	1.0000
19:36194333:T:C	acceptor_gain	1.0000
19:36194333:T:TC	acceptor_gain	1.0000
19:36194337:A:T	acceptor_gain	1.0000
19:36195024:CCTTA:C	donor_loss	1.0000
19:36195025:CTTA:C	donor_loss	1.0000
19:36195026:TTA:T	donor_loss	1.0000
19:36195027:TA:T	donor_loss	1.0000
19:36195028:A:T	donor_loss	1.0000
19:36195029:C:CT	donor_loss	1.0000
19:36195069:C:A	donor_gain	1.0000
19:36195152:AGTCC:A	acceptor_gain	1.0000
19:36195153:GTCC:G	acceptor_gain	1.0000
19:36195154:TCC:T	acceptor_gain	1.0000
19:36195155:CC:C	acceptor_gain	1.0000
19:36195155:CCC:C	acceptor_gain	1.0000
19:36195156:CC:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000053811 (19:36213760 G>A), RS1000097220 (19:36185627 C>G), RS1000108253 (19:36237342 G>A), RS1000172701 (19:36184713 G>A), RS1000224228 (19:36224305 T>A), RS1000228624 (19:36212630 A>C), RS1000232318 (19:36185369 G>A), RS1000247245 (19:36229971 C>T), RS1000251289 (19:36230943 A>G), RS1000272288 (19:36191607 C>T), RS1000276276 (19:36196795 C>T), RS1000382618 (19:36243270 G>C), RS1000395278 (19:36218953 C>T), RS1000411385 (19:36224682 G>C), RS1000421858 (19:36197258 C>A,T)

Disease associations

OMIM: gene MIM:614275 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90007006_11	Gut microbiota relative abundance (unclassified genus belonging to family Erysipelotrichaceae)	5.000000e-07
GCST90007006_5	Gut microbiota relative abundance (unclassified genus belonging to family Erysipelotrichaceae)	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4805162	Efficacy	3	methylphenidate	Attention Deficit Disorder with Hyperactivity

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4805162	ZNF565	3	0.00	1	methylphenidate

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	2
bisphenol A	decreases expression	1
cupric oxide	increases expression	1
Sunitinib	increases expression	1
Formaldehyde	decreases expression	1
Quercetin	decreases expression	1
Dronabinol	decreases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety