ZNF503

Summary

ZNF503 (zinc finger protein 503, HGNC:23589) is a protein-coding gene on chromosome 10q22.2, encoding Zinc finger protein 503 (Q96F45). May function as a transcriptional repressor.

Predicted to enable zinc ion binding activity. Involved in G1 to G0 transition involved in cell differentiation; negative regulation of cell population proliferation; and negative regulation of gene expression. Predicted to be active in nucleus.

Source: NCBI Gene 84858 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 125 total
• MANE Select transcript: NM_032772

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23589
Approved symbol	ZNF503
Name	zinc finger protein 503
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	ZPO2, ZEPPO2, FLJ45745, MGC2555, Nlz2
Ensembl gene	ENSG00000165655
Ensembl biotype	protein_coding
OMIM	613902
Entrez	84858

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372524

RefSeq mRNA: 1 — MANE Select: NM_032772 NM_032772

CCDS: CCDS7350

Canonical transcript exons

ENST00000372524 — 2 exons

Exon	Start	End
ENSE00001458022	75397830	75400374
ENSE00001813348	75401105	75401764

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9761 / max 309.8397, expressed in 1619 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110147	19.8457	1551
110148	4.5104	1251
110146	1.4964	905
110149	0.8669	448
110151	0.4591	256
205906	0.4435	216
110150	0.3541	173

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	98.62	gold quality
seminal vesicle	UBERON:0000998	98.52	gold quality
cardia of stomach	UBERON:0001162	97.97	gold quality
tendon of biceps brachii	UBERON:0008188	97.67	gold quality
kidney epithelium	UBERON:0004819	97.60	gold quality
pylorus	UBERON:0001166	96.87	gold quality
lower lobe of lung	UBERON:0008949	96.86	gold quality
pancreatic ductal cell	CL:0002079	96.66	gold quality
nipple	UBERON:0002030	96.43	gold quality
pigmented layer of retina	UBERON:0001782	96.20	gold quality
urethra	UBERON:0000057	95.90	gold quality
pericardium	UBERON:0002407	95.69	gold quality
trachea	UBERON:0003126	95.62	gold quality
trigeminal ganglion	UBERON:0001675	94.62	gold quality
decidua	UBERON:0002450	94.29	gold quality
layer of synovial tissue	UBERON:0007616	94.17	gold quality
caput epididymis	UBERON:0004358	94.05	gold quality
corpus epididymis	UBERON:0004359	94.01	gold quality
synovial joint	UBERON:0002217	93.93	gold quality
mammary duct	UBERON:0001765	93.58	gold quality
cauda epididymis	UBERON:0004360	93.49	gold quality
epithelium of mammary gland	UBERON:0003244	93.46	gold quality
penis	UBERON:0000989	93.38	gold quality
dorsal root ganglion	UBERON:0000044	93.28	gold quality
pharyngeal mucosa	UBERON:0000355	92.97	gold quality
skin of hip	UBERON:0001554	92.87	gold quality
right ovary	UBERON:0002118	92.80	gold quality
superficial temporal artery	UBERON:0001614	92.50	gold quality
germinal epithelium of ovary	UBERON:0001304	92.43	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	1171.63
E-HCAD-5	yes	492.93
E-HCAD-10	yes	19.61
E-GEOD-81608	yes	8.75
E-ANND-3	yes	8.70

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CDH1	Repression
GATA3	Repression
ZNF503	Repression

Upstream regulators (CollecTRI, top): GLI3, ZNF503

miRNA regulators (miRDB)

154 targeting ZNF503, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 4)

• We have identified ZPO2 as a negative regulator of GATA3, thus providing an alternative mechanism that results in a reduction in or perhaps even loss of GATA3 during breast cancer development. (PMID:28258171)
• Long non-coding RNA ZNF503-AS1 promotes retinal pigment epithelial cells differentiation by downregulating ZNF503 expression. (PMID:28880276)
• miR-340-5p inhibits NCI-H1650 cell proliferation and invasion by directly targeting ZNF503 and that miR-340-5p can serve as a potential therapeutic target for treating non-small cell lung cancer. (PMID:31160893)
• ZNF503 combined with GATA3 is a prognostic factor in triple-negative breast cancer. (PMID:37036735)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf503	ENSDARG00000018492
mus_musculus	Zfp503	ENSMUSG00000039081
rattus_norvegicus	Zfp503	ENSRNOG00000014237
drosophila_melanogaster	elB	FBGN0004858
drosophila_melanogaster	noc	FBGN0005771
caenorhabditis_elegans		WBGENE00006580

Paralogs (1): ZNF703 (ENSG00000183779)

Protein

Protein identifiers

Zinc finger protein 503 — Q96F45 (reviewed: Q96F45)

All UniProt accessions (1): Q96F45

UniProt curated annotations — full annotation on UniProt →

Function. May function as a transcriptional repressor.

Subcellular location. Nucleus.

Similarity. Belongs to the Elbow/Noc family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96F45-1	1	yes
Q96F45-2	2
Q96F45-3	3

RefSeq proteins (1): NP_116161* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR022129	Tscrpt_rep_NocA-like	Family
IPR051520	Elbow/Noc_ZnFinger	Family

Pfam: PF12402

UniProt features (24 total): compositionally biased region 12, modified residue 5, region of interest 2, splice variant 2, chain 1, zinc finger region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96F45-F1	49.59	0.03

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 (5): 102, 209, 231, 237, 636

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 213 (showing top): MYAATNNNNNNNGGC_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, TGCGCANK_UNKNOWN, E2F4DP1_01, GCANCTGNY_MYOD_Q6, AREB6_03, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, SENESE_HDAC1_AND_HDAC2_TARGETS_DN

GO Biological Process (5): negative regulation of cell population proliferation (GO:0008285), negative regulation of gene expression (GO:0010629), negative regulation of DNA-templated transcription (GO:0045892), neural precursor cell proliferation (GO:0061351), G1 to G0 transition involved in cell differentiation (GO:0070315)

GO Molecular Function (3): zinc ion binding (GO:0008270), 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
cell population proliferation	2
regulation of cell population proliferation	1
negative regulation of cellular process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cell differentiation	1
G1 to G0 transition	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF503	ISL1	P20663	553
ZNF503	TEP1	Q99973	552
ZNF503	DACT3	Q96B18	462
ZNF503	COMTD1	Q86VU5	415
ZNF503	SYT7	O43581	402
ZNF503	GSX2	Q9BZM3	397
ZNF503	USP9X	Q93008	386
ZNF503	GSX1	Q9H4S2	379
ZNF503	MEIS2	O14770	376
ZNF503	VMA12	Q8N511	365
ZNF503	BCL11B	Q9C0K0	361
ZNF503	OTX2	P32243	342
ZNF503	TSHZ3	Q63HK5	341
ZNF503	TSHZ2	Q9NRE2	340
ZNF503	TPSG1	Q9NRR2	335

IntAct

75 interactions, top by confidence:

A	B	Type	Score
rep	GTF2F2	psi-mi:“MI:0914”(association)	0.730
DCAF7	DIAPH1	psi-mi:“MI:0914”(association)	0.730
ZNF503	rep	psi-mi:“MI:0915”(physical association)	0.660
DCK	DGUOK	psi-mi:“MI:0914”(association)	0.620
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
ATN1	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
ARID5A	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
TLE5	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
ZNF503	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
TENT5B	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
DTX2	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
PROP1	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-1	ZNF503	psi-mi:“MI:0915”(physical association)	0.560
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
ZNF503	ARID1B	psi-mi:“MI:0915”(physical association)	0.400
Snrnp70	GEMIN2	psi-mi:“MI:0914”(association)	0.350
CEP170P1	PCYT1A	psi-mi:“MI:0914”(association)	0.350
KLC1	RBFOX2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSPBP1	HGS	psi-mi:“MI:0914”(association)	0.350
DCAF7	DIAPH1	psi-mi:“MI:0914”(association)	0.350
MED23	PGRMC1	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (74): ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS), ZNF503 (Affinity Capture-MS)

ESM2 similar proteins: O08755, O16011, O43312, O60422, O77638, O88532, O88942, O95948, P0CL69, P17544, P54288, P70512, P98201, Q01826, Q02930, Q08289, Q08DV5, Q13469, Q3UR85, Q5R9C9, Q5REX3, Q5VTB9, Q60591, Q60611, Q6NT76, Q6P1E1, Q6P9S0, Q6PDX6, Q6UFS5, Q6UUV9, Q6XBJ3, Q765P7, Q7TMA2, Q8BIE6, Q8BJA3, Q8C0V0, Q8CIE2, Q8HXD5, Q8K557, Q8NF64

Diamond homologs: P0CL69, Q05AQ8, Q24423, Q2VPM4, Q566L4, Q6UFS5, Q7TMA2, Q7ZWN6, Q90ZE2, Q96F45, Q9H7S9, Q9VJS8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ZNF503	“down-regulates quantity by repression”	GATA3	“transcriptional regulation”
ZNF503	“down-regulates quantity by repression”	CDH1	“transcriptional regulation”
ZNF503	“up-regulates activity”	PTK2
TLE5	“down-regulates activity”	ZNF503	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
cell fate commitment	5	28.4×	1e-04
anatomical structure morphogenesis	6	16.1×	2e-04
transcription by RNA polymerase II	9	12.2×	1e-05
central nervous system development	5	11.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	116
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

166 predictions. Top by Δscore:

Variant	Effect	Δscore
10:75400405:C:CT	acceptor_gain	1.0000
10:75401100:CTTA:C	donor_loss	1.0000
10:75401101:TTAC:T	donor_loss	1.0000
10:75401102:TAC:T	donor_loss	1.0000
10:75401104:CCT:C	donor_gain	1.0000
10:75400370:TCGAG:T	acceptor_gain	0.9900
10:75400371:CGAGC:C	acceptor_gain	0.9900
10:75400384:C:CT	acceptor_gain	0.9900
10:75400402:C:CT	acceptor_gain	0.9900
10:75400407:C:CT	acceptor_gain	0.9900
10:75400409:C:CT	acceptor_gain	0.9900
10:75401103:A:AC	donor_gain	0.9900
10:75401104:C:CC	donor_gain	0.9900
10:75400371:CGAG:C	acceptor_gain	0.9800
10:75400374:GC:G	acceptor_loss	0.9800
10:75400375:C:CC	acceptor_gain	0.9800
10:75400375:CTGCG:C	acceptor_loss	0.9800
10:75400376:T:C	acceptor_loss	0.9800
10:75400403:G:T	acceptor_gain	0.9800
10:75401103:AC:A	donor_gain	0.9800
10:75401104:CC:C	donor_gain	0.9800
10:75401104:CCTCG:C	donor_gain	0.9800
10:75400373:AG:A	acceptor_gain	0.9700
10:75400388:CGA:C	acceptor_gain	0.9700
10:75400390:A:AC	acceptor_gain	0.9700
10:75400410:A:T	acceptor_gain	0.9700
10:75400372:GAG:G	acceptor_gain	0.9600
10:75400378:C:CT	acceptor_gain	0.9600
10:75400389:G:T	acceptor_gain	0.9600
10:75400390:A:C	acceptor_gain	0.9600

AlphaMissense

4068 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:75399066:G:C	H542D	1.000
10:75399074:A:G	L539S	1.000
10:75399078:G:C	H538D	1.000
10:75399086:A:G	L535P	1.000
10:75399103:G:C	F529L	1.000
10:75399103:G:T	F529L	1.000
10:75399104:A:G	F529S	1.000
10:75399105:A:G	F529L	1.000
10:75399115:G:C	C525W	1.000
10:75399116:C:A	C525F	1.000
10:75399116:C:G	C525S	1.000
10:75399116:C:T	C525Y	1.000
10:75399117:A:G	C525R	1.000
10:75399117:A:T	C525S	1.000
10:75399136:C:A	W518C	1.000
10:75399136:C:G	W518C	1.000
10:75399138:A:G	W518R	1.000
10:75399138:A:T	W518R	1.000
10:75399142:G:C	C516W	1.000
10:75399143:C:A	C516F	1.000
10:75399143:C:G	C516S	1.000
10:75399143:C:T	C516Y	1.000
10:75399144:A:G	C516R	1.000
10:75399144:A:T	C516S	1.000
10:75399394:G:C	C432W	1.000
10:75399396:A:G	C432R	1.000
10:75399409:G:C	C427W	1.000
10:75399410:C:T	C427Y	1.000
10:75399411:A:G	C427R	1.000
10:75400054:G:C	F212L	1.000

dbSNP variants (sampled 300 via entrez): RS1000013927 (10:75313146 T>C), RS1000016272 (10:75336752 T>C), RS1000017022 (10:75395922 G>GA), RS1000020860 (10:75402184 G>A), RS1000040967 (10:75403746 C>A,T), RS1000060018 (10:75366310 G>A,T), RS1000071256 (10:75309386 T>A), RS1000126733 (10:75359274 C>T), RS1000132856 (10:75353849 C>G), RS1000171610 (10:75371686 G>A,T), RS1000173764 (10:75399910 C>G,T), RS1000175959 (10:75316598 C>G), RS1000179992 (10:75361685 T>A), RS1000232259 (10:75361308 A>T), RS1000269829 (10:75390171 A>G)

Disease associations

OMIM: gene MIM:613902 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007847_96	Type 2 diabetes	2.000000e-09
GCST009391_1783	Metabolite levels	3.000000e-07
GCST010244_419	Triglyceride levels	8.000000e-10
GCST90026415_10	Mild obesity-related type 2 diabetes	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004468	glucose measurement
EFO:0010477	fructose measurement
EFO:0010481	galactose measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Cisplatin	increases expression, decreases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
dimethylselenide	increases oxidation, increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
vanadyl sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	affects reaction, affects expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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