ZNF154

Summary

ZNF154 (zinc finger protein 154, HGNC:12939) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger protein 154 (Q13106). May be involved in transcriptional regulation.

This gene encodes a protein that belongs to the zinc finger Kruppel family of transcriptional regulators, whose members are thought to function in normal and abnormal cell growth and differentiation. Hypermethylation of this gene is associated with the recurrence of non muscle invasive bladder cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7710 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_001085384

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12939
Approved symbol	ZNF154
Name	zinc finger protein 154
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	pHZ-92
Ensembl gene	ENSG00000179909
Ensembl biotype	protein_coding
OMIM	604085
Entrez	7710

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000451275, ENST00000512439, ENST00000684351

RefSeq mRNA: 1 — MANE Select: NM_001085384 NM_001085384

CCDS: CCDS42639

Canonical transcript exons

ENST00000684351 — 3 exons

Exon	Start	End
ENSE00003026227	57704853	57704979
ENSE00003918416	57708939	57709204
ENSE00003918934	57696275	57702788

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 88.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.3629 / max 165.0067, expressed in 970 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182911	5.3629	970

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	88.43	gold quality
ganglionic eminence	UBERON:0004023	87.32	gold quality
ventricular zone	UBERON:0003053	82.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.63	gold quality
adrenal tissue	UBERON:0018303	80.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	79.62	gold quality
lower esophagus	UBERON:0013473	79.60	gold quality
left lobe of thyroid gland	UBERON:0001120	79.10	gold quality
right lobe of thyroid gland	UBERON:0001119	78.38	gold quality
adenohypophysis	UBERON:0002196	77.57	gold quality
thyroid gland	UBERON:0002046	77.54	gold quality
cerebellar hemisphere	UBERON:0002245	77.36	gold quality
cerebellar cortex	UBERON:0002129	77.27	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.12	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.94	gold quality
apex of heart	UBERON:0002098	76.91	gold quality
right atrium auricular region	UBERON:0006631	75.76	gold quality
left adrenal gland cortex	UBERON:0035825	75.38	gold quality
right adrenal gland cortex	UBERON:0035827	75.30	gold quality
right adrenal gland	UBERON:0001233	75.03	gold quality
left adrenal gland	UBERON:0001234	74.97	gold quality
cardiac atrium	UBERON:0002081	74.86	gold quality
pituitary gland	UBERON:0000007	74.57	gold quality
bone marrow cell	CL:0002092	74.27	gold quality
cerebellum	UBERON:0002037	74.27	gold quality
adrenal gland	UBERON:0002369	74.09	gold quality
gall bladder	UBERON:0002110	73.29	gold quality
spleen	UBERON:0002106	73.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.00	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	498.30
E-MTAB-7303	no	151.10
E-ANND-3	no	4.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

178 targeting ZNF154, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 6)

• Methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens are promising diagnostic biomarkers for bladder cancer recurrence surveillance (PMID:23056278)
• Epigenetic modifications affecting the promoters of ZNF154, CASP8, and VHL are shared across a vast array of tumor types and may therefore be important for understanding the genomic landscape of cancer. (PMID:24149212)
• Hypermethylation level of ZNF154 lead to gene expression inhibition and function loss, which contribute to the development and poor outcomes in Prostate cancer. In addition, the mean methylation level of ZNF154 can be used as an independent risk factor to predict biochemical recurrence. (PMID:29966681)
• Data show a significant association between zinc finger protein 154 (ZNF154) promoter hypermethylation and better postoperative survival. (PMID:31683647)
• Assessing ZNF154 methylation in patient plasma as a multicancer marker in liquid biopsies from colon, liver, ovarian and pancreatic cancer patients. (PMID:33420235)
• Targeted demethylation at ZNF154 promotor upregulates ZNF154 expression and inhibits the proliferation and migration of Esophageal Squamous Carcinoma cells. (PMID:36064578)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfx	ENSDARG00000074453
danio_rerio		ENSDARG00000098424
mus_musculus	Zfy2	ENSMUSG00000000103
mus_musculus	Zfy1	ENSMUSG00000053211
rattus_norvegicus	Zfy1	ENSRNOG00000053042

Paralogs (38): ZFX (ENSG00000005889), ZBTB11 (ENSG00000066422), ZFAT (ENSG00000066827), ZFY (ENSG00000067646), ZNF586 (ENSG00000083828), IKZF5 (ENSG00000095574), ZNF419 (ENSG00000105136), ZNF549 (ENSG00000121406), ZSCAN20 (ENSG00000121903), ZNF304 (ENSG00000131845), PRDM15 (ENSG00000141956), ZNF660 (ENSG00000144792), ZNF711 (ENSG00000147180), ZNF773 (ENSG00000152439), ZNF256 (ENSG00000152454), ZNF837 (ENSG00000152475), ZNF691 (ENSG00000164011), ZNF610 (ENSG00000167554), E4F1 (ENSG00000167967), ZNF562 (ENSG00000171466), ZNF561 (ENSG00000171469), ZNF584 (ENSG00000171574), ZIK1 (ENSG00000171649), ZNF570 (ENSG00000171827), ZSCAN2 (ENSG00000176371), ZNF552 (ENSG00000178935), ZNF792 (ENSG00000180884), ZNF793 (ENSG00000188227), ZNF548 (ENSG00000188785), ZNF79 (ENSG00000196152), ZNF418 (ENSG00000196724), ZNF772 (ENSG00000197128), ZNF583 (ENSG00000198440), ZNF480 (ENSG00000198464), ZNF551 (ENSG00000204519), ZNF134 (ENSG00000213762), ZNF587B (ENSG00000269343), ZNF8 (ENSG00000278129)

Protein

Protein identifiers

Zinc finger protein 154 — Q13106 (reviewed: Q13106)

All UniProt accessions (1): Q13106

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_001078853* (*=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 (22 total): zinc finger region 12, sequence variant 4, sequence conflict 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13106-F1	71.45	0.32

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 58 (showing top): MORF_ZNF10, MORF_EPHA7, MORF_RAB3A, MORF_WNT1, MORF_DCC, MORF_FRK, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, HATADA_METHYLATED_IN_LUNG_CANCER_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, KRAS.600_UP.V1_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, PRKDC_TARGET_GENES, MIR651_3P, MIR1827

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), regulation of DNA-templated transcription (GO:0006355)

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 (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
regulation of DNA-templated transcription	2
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
negative regulation of RNA biosynthetic process	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
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF154	STEAP4	Q687X5	575
ZNF154	POU4F2	Q12837	549
ZNF154	ANKRD53	Q8N9V6	543
ZNF154	NID2	Q14112	497
ZNF154	EOMES	O95936	490
ZNF154	NXPE3	Q969Y0	479
ZNF154	CDKL2	Q92772	472
ZNF154	SEPTIN9	Q9UHD8	462
ZNF154	FAM78A	Q5JUQ0	447
ZNF154	ALKAL1	Q6UXT8	446
ZNF154	RIMS4	Q9H426	444
ZNF154	HOXA9	P31269	432
ZNF154	PCDH17	O14917	419
ZNF154	RASSF1	Q9NS23	390
ZNF154	PRAC1	Q96KF2	376

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ZNF154	A2ML1	psi-mi:“MI:0914”(association)	0.350
dacD	ZNF154	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): S100A7 (Affinity Capture-MS), AZGP1 (Affinity Capture-MS), GDA (Affinity Capture-MS), ALOX12B (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), CAPNS2 (Affinity Capture-MS), CTSH (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), SMTNL2 (Affinity Capture-MS), IL36G (Affinity Capture-MS), HAL (Affinity Capture-MS), A2ML1 (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS), CRNN (Affinity Capture-MS)

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: A2RRD8, A6NFI3, A6NM28, A8MUZ8, A8MWA4, B2RUI1, B4DU55, E9Q8G5, O43296, O43361, O75467, O75820, P0CH99, P0CI00, P10078, P16373, P16374, P17021, P17023, P17032, P17097, P17098, P21506, P51786, P52740, Q06732, Q08ER8, Q13106, Q13360, Q13398, Q14592, Q147U1, Q32M78, Q3KQV3, Q3MIS6, Q3SY52, Q571J5, Q5CZA5, Q5HY98, Q5R7I8

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	59
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

741 predictions. Top by Δscore:

Variant	Effect	Δscore
19:57708935:TCA:T	donor_loss	1.0000
19:57708937:A:AC	donor_gain	1.0000
19:57708938:C:CA	donor_gain	1.0000
19:57708938:C:T	donor_loss	1.0000
19:57704846:ACCTT:A	donor_loss	0.9900
19:57704847:CCTTA:C	donor_loss	0.9900
19:57704848:CTTAC:C	donor_loss	0.9900
19:57704849:TTACC:T	donor_loss	0.9900
19:57704850:TA:T	donor_loss	0.9900
19:57708937:AC:A	donor_gain	0.9900
19:57708938:CC:C	donor_gain	0.9900
19:57708938:CCT:C	donor_gain	0.9900
19:57708938:CCTG:C	donor_gain	0.9900
19:57708938:CCTGA:C	donor_gain	0.9900
19:57702786:CAT:C	acceptor_gain	0.9800
19:57702655:G:GT	donor_gain	0.9700
19:57697837:CACAG:C	acceptor_gain	0.9600
19:57708934:CTCA:C	donor_gain	0.9600
19:57697839:CAG:C	acceptor_gain	0.9500
19:57702787:ATC:A	acceptor_loss	0.9500
19:57702788:TCT:T	acceptor_loss	0.9500
19:57702789:CT:C	acceptor_loss	0.9500
19:57704975:GTGCC:G	acceptor_loss	0.9500
19:57704979:CCT:C	acceptor_loss	0.9500
19:57704980:CTGC:C	acceptor_loss	0.9500
19:57704981:T:A	acceptor_loss	0.9500
19:57702789:C:CC	acceptor_gain	0.9400
19:57702791:G:C	acceptor_loss	0.9400
19:57704982:G:C	acceptor_loss	0.9400
19:57701156:A:T	acceptor_gain	0.9300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000213914 (19:57695995 T>C), RS1000695633 (19:57698538 A>G), RS1000965705 (19:57707489 C>G), RS1001072580 (19:57700034 T>C), RS1001524864 (19:57711159 A>G), RS1001641586 (19:57708997 G>A), RS1002234256 (19:57699654 C>A,T), RS1002244500 (19:57710342 A>T), RS1002690233 (19:57706726 G>C), RS1002775130 (19:57697340 A>G), RS1002900256 (19:57697208 C>G), RS1002915505 (19:57707775 G>A), RS1002973134 (19:57710151 G>T), RS1003093232 (19:57701373 C>T), RS1003144065 (19:57700807 G>A)

Disease associations

OMIM: gene MIM:604085 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
nickel sulfate	decreases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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