ZNF175

Summary

ZNF175 (zinc finger protein 175, HGNC:12964) is a protein-coding gene on chromosome 19q13.41, encoding Zinc finger protein 175 (Q9Y473). Down-regulates the expression of several chemokine receptors.

Enables DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleolus.

Source: NCBI Gene 7728 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 92 total
• MANE Select transcript: NM_007147

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12964
Approved symbol	ZNF175
Name	zinc finger protein 175
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	OTK18
Ensembl gene	ENSG00000105497
Ensembl biotype	protein_coding
OMIM	601139
Entrez	7728

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000262259, ENST00000436511, ENST00000545217, ENST00000596504, ENST00000600460, ENST00000912771, ENST00000958253, ENST00000958254

RefSeq mRNA: 1 — MANE Select: NM_007147 NM_007147

CCDS: CCDS12837

Canonical transcript exons

ENST00000262259 — 5 exons

Exon	Start	End
ENSE00000842706	51573150	51573401
ENSE00000842707	51586627	51592510
ENSE00002436360	51581391	51581517
ENSE00003711436	51581787	51581882
ENSE00003842059	51571283	51571475

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 88.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8490 / max 110.7990, expressed in 1351 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177230	3.7888	1348
177231	0.0602	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.90	silver quality
inferior olivary complex	UBERON:0002127	87.11	silver quality
germinal epithelium of ovary	UBERON:0001304	83.54	gold quality
esophagus squamous epithelium	UBERON:0006920	83.35	gold quality
caput epididymis	UBERON:0004358	83.07	gold quality
corpus epididymis	UBERON:0004359	82.99	gold quality
medial globus pallidus	UBERON:0002477	82.75	silver quality
cardia of stomach	UBERON:0001162	82.52	silver quality
tibia	UBERON:0000979	82.43	gold quality
cauda epididymis	UBERON:0004360	82.36	gold quality
stromal cell of endometrium	CL:0002255	82.16	gold quality
triceps brachii	UBERON:0001509	81.79	gold quality
medulla oblongata	UBERON:0001896	81.71	silver quality
globus pallidus	UBERON:0001875	81.65	silver quality
ventricular zone	UBERON:0003053	81.51	gold quality
gluteal muscle	UBERON:0002000	81.37	gold quality
hair follicle	UBERON:0002073	81.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.23	gold quality
trabecular bone tissue	UBERON:0002483	81.18	gold quality
pericardium	UBERON:0002407	80.99	gold quality
ventral tegmental area	UBERON:0002691	80.78	silver quality
superior surface of tongue	UBERON:0007371	80.71	silver quality
superior vestibular nucleus	UBERON:0007227	80.56	silver quality
parietal pleura	UBERON:0002400	80.39	gold quality
subthalamic nucleus	UBERON:0001906	80.20	silver quality
cortical plate	UBERON:0005343	80.07	gold quality
mammary duct	UBERON:0001765	80.04	silver quality
vena cava	UBERON:0004087	79.95	gold quality
islet of Langerhans	UBERON:0000006	79.82	gold quality
choroid plexus epithelium	UBERON:0003911	79.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.17

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
NTF3	Activation

JASPAR motifs

Motif	Name	Family
MA2332.1	ZNF175	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:27852650

Upstream regulators (CollecTRI, top): ETS1, FOXD3, STAT1, YY1

miRNA regulators (miRDB)

60 targeting ZNF175, 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-190A-3P	100.00	80.35	5520
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4728-3P	99.47	68.94	981

Literature-anchored findings (GeneRIF, showing 7)

• Transcriptional suppressor OTK18 plays a role in macrophage control of viral replication during advanced HIV-1 infection. (PMID:14688346)
• OTK18/zinc finger protein 175 expression in brain mononuclear phagocytes is a signature for advanced HIV-1 encephalitis. (PMID:15081264)
• Plasma OTK18 levels are positively correlated to CD8 T-cell counts, independent of HIV-1 status. (PMID:18773297)
• These results suggest a role for OTK18 in innate immunity. (PMID:18776638)
• These data suggest that calpain and proteasome are involved in OTK18 endoproteolysis and degradation (PMID:19034669)
• HIV-1 induces OTK18 expression through a YIN-YANG-1 mediated manner in human macrophages (PMID:19034670)
• OTK18 may play a role in neurotrophin production and consequently support neuronal survival. (PMID:19247725)

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), 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), ZNF3 (ENSG00000166526)

Protein

Protein identifiers

Zinc finger protein 175 — Q9Y473 (reviewed: Q9Y473)

Alternative names: Zinc finger protein OTK18

All UniProt accessions (4): Q9Y473, F5GZI7, G3V1K8, M0R013

UniProt curated annotations — full annotation on UniProt →

Function. Down-regulates the expression of several chemokine receptors. Interferes with HIV-1 replication by suppressing Tat-induced viral LTR promoter activity.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Induction. By HIV-1 infection.

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

RefSeq proteins (1): NP_009078* (*=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 (23 total): zinc finger region 15, sequence variant 3, chain 1, domain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y473-F1	61.67	0.15

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 109 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, RODRIGUES_NTN1_TARGETS_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_DEFENSE_RESPONSE_TO_VIRUS, MODULE_48, MODULE_95, CETS1P54_01, GOBP_RESPONSE_TO_VIRUS, GOCC_NUCLEOLUS, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of transcription by RNA polymerase II (GO:0045944), defense response to virus (GO:0051607), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleolus (GO:0005730), cytosol (GO:0005829), nucleus (GO:0005634), cytoplasm (GO:0005737)

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 transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
positive regulation of DNA-templated transcription	1
defense response	1
response to virus	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
DNA binding	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF175	MRFAP1L1	Q96HT8	368
ZNF175	FHL5	Q5TD97	330
ZNF175	REP15	Q6BDI9	305
ZNF175	LYPD5	Q6UWN5	303
ZNF175	UBTD1	Q9HAC8	289
ZNF175	C9JR48	C9JR48	287
ZNF175	SBSPON	Q8IVN8	286
ZNF175	SNURF	Q9Y675	285
ZNF175	B3GNT4	Q9C0J1	276
ZNF175	NCMAP	Q5T1S8	272
ZNF175	ZMYM6	O95789	269
ZNF175	MYO7B	Q6PIF6	269
ZNF175	K7ELM3	K7ELM3	268
ZNF175	CCSAP	Q6IQ19	253
ZNF175	SIGLEC6	O43699	250

IntAct

28 interactions, top by confidence:

A	B	Type	Score
ALAS1	ZNF175	psi-mi:“MI:0915”(physical association)	0.720
ZNF175	ALAS1	psi-mi:“MI:0915”(physical association)	0.720
ZNF250	ZNF175	psi-mi:“MI:0915”(physical association)	0.560
ZNF264	ZNF175	psi-mi:“MI:0915”(physical association)	0.560
PSTPIP1	ZNF175	psi-mi:“MI:0915”(physical association)	0.560
ZNF175	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
ZNF175	ZNF250	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	ZNF175	psi-mi:“MI:0915”(physical association)	0.560
ZNF175	ZNF264	psi-mi:“MI:0915”(physical association)	0.560
ZNF175	SNX16	psi-mi:“MI:0915”(physical association)	0.400
ZNF175	LZTR1	psi-mi:“MI:0915”(physical association)	0.370
LPXN	ZNF175	psi-mi:“MI:0915”(physical association)	0.370
NDEL1	ZNF175	psi-mi:“MI:0915”(physical association)	0.000
ZNF264	ZNF175	psi-mi:“MI:0915”(physical association)	0.000
ZNF175	ALAS1	psi-mi:“MI:0915”(physical association)	0.000
CDC42	ZNF175	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): ZNF175 (Two-hybrid), PSTPIP1 (Two-hybrid), ZNF264 (Two-hybrid), ZNF250 (Two-hybrid), KRTAP10-7 (Two-hybrid), ZNF175 (Synthetic Lethality), ZNF175 (Two-hybrid), ZNF175 (Two-hybrid), SNX16 (Affinity Capture-MS), ZNF175 (Affinity Capture-RNA), ZNF175 (Affinity Capture-MS), EXO1 (Negative Genetic), ZNF175 (Positive Genetic), PPIA (Cross-Linking-MS (XL-MS)), ZNF175 (Two-hybrid)

ESM2 similar proteins: A0A087WUV0, A0JNB1, A2VDP4, B2RUI1, P0CG31, P10072, P17025, P17036, P17097, P18733, P51814, Q08ER8, Q09FC8, Q0VGE8, Q14590, Q15937, Q16600, Q2M3X9, Q4V8A8, Q5CZA5, Q5R8G9, Q5RBX0, Q5VIY5, Q68DI1, Q6J6I6, Q6NX49, Q6P1L6, Q6PG37, Q6ZMS4, Q6ZMW2, Q80YP6, Q86UD4, Q86Y25, Q8IZ26, Q8N184, Q8NB42, Q8NEK5, Q8TAF7, Q8TF47, Q8WXB4

Diamond homologs: A0JPL0, A2VDP4, A6QLU5, A6QPT6, A8MQ14, A8MUZ8, A8MWA4, B1APH4, B2RXC5, E9PYI1, E9Q8G5, O75290, O94892, P08042, P0CH99, P0CI00, P17014, P17025, P17030, P17031, P17032, P17098, P21506, P51508, P51523, P51786, P51814, P52736, P52738, Q02525, Q03923, Q03936, Q06730, Q06732, Q0VCB0, Q13401, Q14587, Q16587, Q2M218, Q2M3X9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

752 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51581879:CAAG:C	donor_loss	1.0000
19:51581881:AGGT:A	donor_loss	1.0000
19:51581884:T:A	donor_loss	1.0000
19:51580551:A:T	donor_gain	0.9900
19:51581514:GTGG:G	donor_gain	0.9900
19:51581605:G:GG	donor_gain	0.9900
19:51581785:AG:A	acceptor_gain	0.9900
19:51581786:GG:G	acceptor_gain	0.9900
19:51581883:GTGA:G	donor_gain	0.9900
19:51581887:G:GG	donor_gain	0.9900
19:51571472:TGAGG:T	donor_loss	0.9800
19:51571477:T:A	donor_loss	0.9800
19:51581785:A:AG	acceptor_gain	0.9800
19:51581786:G:GG	acceptor_gain	0.9800
19:51581803:CCCAG:C	acceptor_gain	0.9800
19:51581807:G:C	acceptor_gain	0.9800
19:51583378:G:GT	donor_gain	0.9800
19:51581513:A:AG	donor_gain	0.9700
19:51581784:C:G	acceptor_loss	0.9700
19:51581785:A:C	acceptor_loss	0.9700
19:51581876:TGTCA:T	donor_gain	0.9700
19:51581885:GA:G	donor_gain	0.9700
19:51571478:GAGT:G	donor_loss	0.9600
19:51581388:C:CG	acceptor_loss	0.9600
19:51581389:A:T	acceptor_loss	0.9600
19:51581390:G:C	acceptor_loss	0.9600
19:51581786:GGGT:G	acceptor_gain	0.9600
19:51581886:A:AG	donor_gain	0.9600
19:51583404:G:GT	donor_gain	0.9600
19:51581329:T:G	acceptor_gain	0.9500

AlphaMissense

4786 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51587815:G:C	R495P	0.997
19:51587865:T:C	F512L	0.997
19:51587867:C:A	F512L	0.997
19:51587867:C:G	F512L	0.997
19:51587949:T:C	F540L	0.997
19:51587951:C:A	F540L	0.997
19:51587951:C:G	F540L	0.997
19:51588067:G:C	R579P	0.997
19:51587781:T:C	F484L	0.996
19:51587783:C:A	F484L	0.996
19:51587783:C:G	F484L	0.996
19:51587800:T:C	L490P	0.996
19:51587884:T:C	L518P	0.996
19:51588033:T:C	F568L	0.996
19:51588035:C:A	F568L	0.996
19:51588035:C:G	F568L	0.996
19:51588039:T:C	S570P	0.996
19:51587697:T:C	F456L	0.995
19:51587699:C:A	F456L	0.995
19:51587699:C:G	F456L	0.995
19:51587716:T:C	L462P	0.995
19:51588117:T:C	F596L	0.995
19:51588119:C:A	F596L	0.995
19:51588119:C:G	F596L	0.995
19:51588062:T:A	H577Q	0.994
19:51588062:T:G	H577Q	0.994
19:51588064:A:C	Q578P	0.994
19:51588319:G:C	R663P	0.994
19:51587529:T:C	F400L	0.993
19:51587531:C:A	F400L	0.993

dbSNP variants (sampled 300 via entrez): RS1000070484 (19:51577836 T>A,C), RS1000087142 (19:51583932 T>C), RS1000455032 (19:51573443 G>A), RS1000488307 (19:51591162 C>A,T), RS1000865976 (19:51586616 T>C), RS1000923440 (19:51585737 G>A), RS1001029757 (19:51575311 G>A), RS1001144424 (19:51579926 A>C), RS1001302504 (19:51579598 A>G), RS1001337773 (19:51572310 C>G,T), RS1001360425 (19:51591993 C>T), RS1001476059 (19:51579029 C>A,T), RS1001756868 (19:51591352 G>A), RS1001845960 (19:51578329 G>A,T), RS1002215120 (19:51586366 C>A,G)

Disease associations

OMIM: gene MIM:601139 | 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

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	increases expression, increases abundance	1
Atrazine	decreases expression	1
Doxorubicin	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Lead	decreases expression	1
Manganese	increases abundance, increases expression	1
Methotrexate	affects response to substance	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_HA00	K562 eGFP-ZNF175	Cancer cell line	Female
CVCL_HD13	HEK293 eGFP-ZNF175	Transformed cell line	Female

Clinical trials (associated diseases)

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