ZNF165

Summary

ZNF165 (zinc finger protein 165, HGNC:12953) is a protein-coding gene on chromosome 6p22.1, encoding Zinc finger protein 165 (P49910). May be involved in transcriptional regulation.

This gene encodes a member of the Kruppel family of zinc finger proteins. Members of this DNA-binding protein family act as transcriptional regulators. This gene is located within a cluster of zinc finger family members. The encoded protein may play a role in spermatogenesis.

Source: NCBI Gene 7718 — RefSeq curated summary.

At a glance

• GWAS associations: 32
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_001376491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12953
Approved symbol	ZNF165
Name	zinc finger protein 165
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	ZSCAN7, CT53
Ensembl gene	ENSG00000197279
Ensembl biotype	protein_coding
OMIM	600834
Entrez	7718

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000377325, ENST00000683778, ENST00000893308, ENST00000893309

RefSeq mRNA: 4 — MANE Select: NM_001376491 NM_001376491, NM_001376492, NM_001376493, NM_003447

CCDS: CCDS4643

Canonical transcript exons

ENST00000683778 — 4 exons

Exon	Start	End
ENSE00000848508	28086172	28086310
ENSE00001473554	28088563	28089563
ENSE00001981221	28085481	28085891
ENSE00003916078	28080568	28080970

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 91.30.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9177 / max 18.9456, expressed in 441 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66605	0.7656	382
66606	0.0906	24
66607	0.0467	13
66608	0.0147	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	91.30	gold quality
male germ cell	CL:0000015	89.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.62	gold quality
amniotic fluid	UBERON:0000173	82.28	gold quality
left testis	UBERON:0004533	80.30	gold quality
testis	UBERON:0000473	79.73	gold quality
right testis	UBERON:0004534	79.68	gold quality
mucosa of sigmoid colon	UBERON:0004993	78.17	gold quality
islet of Langerhans	UBERON:0000006	78.02	gold quality
colonic mucosa	UBERON:0000317	73.75	gold quality
pancreas	UBERON:0001264	73.14	gold quality
body of pancreas	UBERON:0001150	72.54	gold quality
rectum	UBERON:0001052	71.40	gold quality
mucosa of transverse colon	UBERON:0004991	70.30	gold quality
bronchial epithelial cell	CL:0002328	70.02	gold quality
lower esophagus mucosa	UBERON:0035834	69.97	gold quality
jejunal mucosa	UBERON:0000399	69.24	gold quality
esophagus squamous epithelium	UBERON:0006920	68.68	gold quality
placenta	UBERON:0001987	68.43	gold quality
corpus epididymis	UBERON:0004359	68.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.08	gold quality
epithelium of bronchus	UBERON:0002031	66.95	gold quality
nephron tubule	UBERON:0001231	66.65	gold quality
esophagus mucosa	UBERON:0002469	66.32	gold quality
bronchus	UBERON:0002185	66.30	gold quality
pituitary gland	UBERON:0000007	66.18	gold quality
epithelium of esophagus	UBERON:0001976	66.03	gold quality
duodenum	UBERON:0002114	65.76	gold quality
adenohypophysis	UBERON:0002196	65.70	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-29	no	376.45
E-CURD-112	no	2.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
PMEPA1	Repression
SMAD7	Repression
SMURF2	Repression

Literature-anchored findings (GeneRIF, showing 4)

• ZNF165 mRNA/protein expression was observed in TCC of human urinary bladder and might be used as a novel diagnostic biomarker and as well a vaccine target in development of urinary bladder cancer specific immunotherapy. (PMID:25214475)
• ZNF165 drives the unrestrained activation of transforming growth factor beta (TGFbeta) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1. (PMID:26567849)
• The testis protein ZNF165 is a SMAD3 cofactor that coordinates oncogenic TGFbeta signaling in triple-negative breast cancer. (PMID:32515734)
• ZNF165 Is Involved in the Regulation of Immune Microenvironment and Promoting the Proliferation and Migration of Hepatocellular Carcinoma by AhR/CYP1A1. (PMID:35692498)

Cross-species orthologs

0 orthologs

Paralogs (30): ZNF263 (ENSG00000006194), ZNF213 (ENSG00000085644), ZNF500 (ENSG00000103199), ZKSCAN1 (ENSG00000106261), ZNF205 (ENSG00000122386), ZSCAN9 (ENSG00000137185), PGBD1 (ENSG00000137338), ZNF215 (ENSG00000149054), ZSCAN12 (ENSG00000158691), ZNF394 (ENSG00000160908), ZNF75A (ENSG00000162086), ZSCAN21 (ENSG00000166529), ZNF232 (ENSG00000167840), ZNF24 (ENSG00000172466), ZNF449 (ENSG00000173275), ZSCAN4 (ENSG00000180532), ZSCAN22 (ENSG00000182318), ZNF75D (ENSG00000186376), ZNF396 (ENSG00000186496), ZNF397 (ENSG00000186812), ZSCAN30 (ENSG00000186814), ZKSCAN4 (ENSG00000187626), ZSCAN23 (ENSG00000187987), ZKSCAN3 (ENSG00000189298), ZSCAN16 (ENSG00000196812), ZSCAN25 (ENSG00000197037), ZSCAN26 (ENSG00000197062), ZKSCAN8 (ENSG00000198315), ZSCAN31 (ENSG00000235109), ZNF853 (ENSG00000236609)

Protein

Protein identifiers

Zinc finger protein 165 — P49910 (reviewed: P49910)

Alternative names: Cancer/testis antigen 53, LD65, Zinc finger and SCAN domain-containing protein 7

All UniProt accessions (2): P49910, Q53Z40

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Expressed specifically in testis.

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

RefSeq proteins (4): NP_001363420, NP_001363421, NP_001363422, NP_003438 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003309	SCAN_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR038269	SCAN_sf	Homologous_superfamily

Pfam: PF00096, PF02023

UniProt features (11 total): zinc finger region 6, cross-link 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49910-F1	58.79	0.06

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 195, 23, 162

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, MUELLER_PLURINET, RHEIN_ALL_GLUCOCORTICOID_THERAPY_UP, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, FISCHER_G2_M_CELL_CYCLE, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, PODAR_RESPONSE_TO_ADAPHOSTIN_UP, HADDAD_T_LYMPHOCYTE_AND_NK_PROGENITOR_UP, NUYTTEN_EZH2_TARGETS_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, CHEN_HOXA5_TARGETS_9HR_UP, SMITH_TERT_TARGETS_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

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), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
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
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF165	SMAD3	P84022	715
ZNF165	CCDC110	Q8TBZ0	623
ZNF165	SPACA3	Q8IXA5	507
ZNF165	FTHL17	Q9BXU8	479
ZNF165	FATE1	Q969F0	478
ZNF165	NKAPL	Q5M9Q1	477
ZNF165	CCDC188	H7C350	471
ZNF165	CPXCR1	Q8N123	447
ZNF165	CT83	Q5H943	432
ZNF165	CT55	Q8WUE5	420
ZNF165	SPMAP2	Q9P2T0	419
ZNF165	ZNF438	Q7Z4V0	397
ZNF165	CSAG2	Q9Y5P2	397
ZNF165	RBM46	Q8TBY0	395
ZNF165	HSPB9	Q9BQS6	395

IntAct

141 interactions, top by confidence:

A	B	Type	Score
ZNF165	YJU2B	psi-mi:“MI:0915”(physical association)	0.770
YJU2B	ZNF165	psi-mi:“MI:0915”(physical association)	0.770
ZNF165	SCAND1	psi-mi:“MI:0915”(physical association)	0.670
ZNF165	ZNF446	psi-mi:“MI:0915”(physical association)	0.670
DVL2	ZNF165	psi-mi:“MI:0915”(physical association)	0.630
HAT2	ZNF165	psi-mi:“MI:0915”(physical association)	0.560
ZNF165	HAT2	psi-mi:“MI:0915”(physical association)	0.560
EMD	ZNF165	psi-mi:“MI:0915”(physical association)	0.560
ZNF165	CYSRT1	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	ZNF165	psi-mi:“MI:0915”(physical association)	0.560
ZNF165	ZNF774	psi-mi:“MI:0915”(physical association)	0.560
ZNF263	ZNF165	psi-mi:“MI:0915”(physical association)	0.560
ZNF165	PICK1	psi-mi:“MI:0915”(physical association)	0.560
PPL	ZNF165	psi-mi:“MI:0915”(physical association)	0.560
ZNF165	CCDC125	psi-mi:“MI:0915”(physical association)	0.560
ZNF165	RNPS1	psi-mi:“MI:0915”(physical association)	0.560
ZNF165	DVL3	psi-mi:“MI:0915”(physical association)	0.560
	ZNF165	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (66): ZNF165 (Two-hybrid), AHCYL1 (Two-hybrid), MID2 (Two-hybrid), ZNF446 (Two-hybrid), GPATCH2L (Two-hybrid), KRT40 (Two-hybrid), FAM124A (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), TCEB3B (Two-hybrid), CCDC85B (Two-hybrid), KAT7 (Two-hybrid), CCDC130 (Two-hybrid), ZNF446 (Two-hybrid), ZNF165 (Two-hybrid)

ESM2 similar proteins: A1YEP8, A1YEV9, A1YFW2, A1YG26, A1YG48, A1YG60, A2T6E3, A2T6V8, A2T712, A2T736, A2T7D2, A2T7F4, A2T7L7, A2T812, A6QNZ0, O14709, O15535, O43296, O43309, P10073, P17023, P17097, P49910, Q07231, Q12901, Q15776, Q16670, Q1LZ87, Q3MJ62, Q53GI3, Q571J5, Q5JNZ3, Q5RAE6, Q5RBX0, Q5RCD9, Q5RJ54, Q7Z7L9, Q86W11, Q8IZ26, Q8NF99

Diamond homologs: A1YEP8, A1YEQ3, A1YEV9, A1YFW2, A1YFW6, A1YG26, A1YG48, A1YG60, A1YGJ4, A1YGK6, A2T6E3, A2T6V8, A2T6W2, A2T712, A2T736, A2T7D2, A2T7D7, A2T7F2, A2T7F4, A2T7L7, A2T812, A6QNZ0, A6QPT6, B2KFW1, O14709, O14771, O14978, O15535, O43309, O60304, O95125, P10073, P17022, P17028, P17029, P17040, P28698, P49910, P51815, P59923

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ZNF165	“down-regulates quantity by repression”	SMAD7	“transcriptional regulation”
ZNF165	“down-regulates quantity by repression”	PMEPA1	“transcriptional regulation”
ZNF165	“down-regulates quantity by repression”	SMURF2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

682 predictions. Top by Δscore:

Variant	Effect	Δscore
6:28085559:G:GT	donor_gain	1.0000
6:28085799:GCC:G	donor_gain	1.0000
6:28085880:GCA:G	donor_gain	1.0000
6:28086242:TC:T	donor_gain	1.0000
6:28088559:TTAG:T	acceptor_loss	1.0000
6:28088560:TAG:T	acceptor_loss	1.0000
6:28088561:A:AG	acceptor_gain	1.0000
6:28088562:G:GA	acceptor_gain	1.0000
6:28088562:G:GT	acceptor_loss	1.0000
6:28088562:GATA:G	acceptor_gain	1.0000
6:28085476:CACA:C	acceptor_loss	0.9900
6:28085477:ACAG:A	acceptor_loss	0.9900
6:28085478:CA:C	acceptor_loss	0.9900
6:28085479:A:AT	acceptor_loss	0.9900
6:28085479:AGAT:A	acceptor_gain	0.9900
6:28085480:GAT:G	acceptor_gain	0.9900
6:28085480:GATG:G	acceptor_gain	0.9900
6:28085877:G:GT	donor_gain	0.9900
6:28085883:G:GG	donor_gain	0.9900
6:28086247:T:G	donor_gain	0.9900
6:28088557:TTTTA:T	acceptor_loss	0.9900
6:28088562:GAT:G	acceptor_gain	0.9900
6:28088562:GATAA:G	acceptor_gain	0.9900
6:28085479:A:AG	acceptor_gain	0.9800
6:28085480:G:GG	acceptor_gain	0.9800
6:28085870:C:T	donor_gain	0.9800
6:28085882:A:AG	donor_gain	0.9800
6:28085887:TCCAG:T	donor_loss	0.9800
6:28085888:CCAG:C	donor_loss	0.9800
6:28085889:CAGG:C	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000403003 (6:28084892 T>C), RS1000604228 (6:28084546 C>G), RS1001106057 (6:28079072 C>A,T), RS1001550902 (6:28086498 A>G), RS1002758034 (6:28082708 T>C,G), RS1002834674 (6:28081095 C>A,T), RS1003431734 (6:28082552 T>A), RS1004331881 (6:28088051 G>C), RS1004361504 (6:28087679 C>A,T), RS1004430486 (6:28080524 C>T), RS1004539922 (6:28085276 A>G), RS1004564072 (6:28082484 C>T), RS1004593898 (6:28085692 G>A), RS1005143903 (6:28089739 A>G), RS1005483614 (6:28089622 C>T)

Disease associations

OMIM: gene MIM:600834 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST003944_27	Hepcidin/ferritin ratio	6.000000e-06
GCST003944_30	Hepcidin/ferritin ratio	8.000000e-06
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_115	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_163	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_166	Autism spectrum disorder or schizophrenia	4.000000e-24
GCST004521_212	Autism spectrum disorder or schizophrenia	5.000000e-14
GCST004521_22	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004521_23	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004521_6	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_73	Autism spectrum disorder or schizophrenia	8.000000e-11
GCST004521_77	Autism spectrum disorder or schizophrenia	1.000000e-19
GCST004750_89	Squamous cell lung carcinoma	2.000000e-10
GCST005541_2	Sarcoidosis (Lofgren’s syndrome vs non-Lofgren’s syndrome)	3.000000e-17
GCST006097_6	Moderate to vigorous physical activity levels	2.000000e-09
GCST008747_172	Estimated glomerular filtration rate	8.000000e-09
GCST008747_39	Estimated glomerular filtration rate	1.000000e-07
GCST008921_6	Asthma and major depressive disorder	1.000000e-09
GCST010002_50	Refractive error	4.000000e-34
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010242_51	HDL cholesterol levels	4.000000e-19
GCST010243_32	Apolipoprotein B levels	4.000000e-19
GCST010245_142	LDL cholesterol levels	4.000000e-21
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007901	hepcidin:ferritin ratio
EFO:0008002	physical activity measurement
EFO:0008111	diet measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement
EFO:0004713	FEV/FVC ratio
EFO:0004980	appendicular lean mass

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
rs9393888	Toxicity	3	opioids	Nausea;Vomiting

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9393888	ZNF165	3	0.00	1	opioids

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	6
Cadmium Chloride	increases abundance, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Cadmium	increases abundance, increases expression	3
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Quercetin	affects cotreatment, increases expression, decreases expression	2
Silicon Dioxide	increases expression	2
Tunicamycin	increases expression	2
Asbestos, Crocidolite	increases expression	2
TAK-243	increases sumoylation	1
fluorene-9-bisphenol	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
geraniol	increases expression	1
methylselenic acid	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
periodate-oxidized adenosine	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
trametinib	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HD12	HEK293 eGFP-ZNF165	Transformed cell line	Female

Clinical trials (associated diseases)

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