ZNF540

Summary

ZNF540 (zinc finger protein 540, HGNC:25331) is a protein-coding gene on chromosome 19q13.13, encoding Zinc finger protein 540 (Q8NDQ6). May act as a transcriptional repressor.

Enables mRNA regulatory element binding translation repressor activity. Involved in negative regulation of DNA-templated transcription and negative regulation of translation. Located in cytosol and nucleoplasm.

Source: NCBI Gene 163255 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 195 total
• MANE Select transcript: NM_001172225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25331
Approved symbol	ZNF540
Name	zinc finger protein 540
Location	19q13.13
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547B0714
Ensembl gene	ENSG00000171817
Ensembl biotype	protein_coding
OMIM	613903
Entrez	163255

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000316433, ENST00000343599, ENST00000586134, ENST00000586792, ENST00000587220, ENST00000589117, ENST00000589285, ENST00000589857, ENST00000590588, ENST00000592533, ENST00000868013, ENST00000868014, ENST00000868015, ENST00000868016

RefSeq mRNA: 3 — MANE Select: NM_001172225 NM_001172225, NM_001172226, NM_152606

CCDS: CCDS54258

Canonical transcript exons

ENST00000316433 — 5 exons

Exon	Start	End
ENSE00002806389	37611513	37614179
ENSE00002896234	37594876	37595095
ENSE00003564217	37601010	37601105
ENSE00003573578	37599626	37599752
ENSE00003607534	37598376	37598456

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 92.69.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2740 / max 200.9506, expressed in 520 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175566	2.8784	496
175562	1.2912	497
175565	0.3957	167

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	92.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.70	gold quality
endothelial cell	CL:0000115	89.40	gold quality
cerebellar hemisphere	UBERON:0002245	88.93	gold quality
cerebellar cortex	UBERON:0002129	88.87	gold quality
cerebellum	UBERON:0002037	88.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.26	gold quality
primary visual cortex	UBERON:0002436	87.98	gold quality
pituitary gland	UBERON:0000007	87.54	gold quality
adenohypophysis	UBERON:0002196	87.42	gold quality
cerebellar vermis	UBERON:0004720	87.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.91	gold quality
occipital lobe	UBERON:0002021	85.76	gold quality
right frontal lobe	UBERON:0002810	84.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.60	gold quality
nucleus accumbens	UBERON:0001882	84.45	gold quality
hypothalamus	UBERON:0001898	83.85	gold quality
frontal cortex	UBERON:0001870	83.54	gold quality
anterior cingulate cortex	UBERON:0009835	83.51	gold quality
neocortex	UBERON:0001950	83.45	gold quality
prefrontal cortex	UBERON:0000451	83.42	gold quality
brain	UBERON:0000955	83.10	gold quality
cortical plate	UBERON:0005343	82.84	gold quality
forebrain	UBERON:0001890	82.82	gold quality
cerebral cortex	UBERON:0000956	82.78	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.39	gold quality
caudate nucleus	UBERON:0001873	82.07	gold quality
left ovary	UBERON:0002119	81.80	gold quality
putamen	UBERON:0001874	81.65	gold quality
left lobe of thyroid gland	UBERON:0001120	81.41	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	24.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting ZNF540, 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-340-5P	100.00	72.50	4437
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-1909-5P	98.94	64.01	484

Literature-anchored findings (GeneRIF, showing 1)

• Taken together, these results suggest that ZNF540 may act as a transcriptional repressor in MAPK signaling pathway to mediate cellular functions. (PMID:16815308)

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 540 — Q8NDQ6 (reviewed: Q8NDQ6)

All UniProt accessions (4): Q8NDQ6, K7EK80, K7EQ46, K7ER55

UniProt curated annotations — full annotation on UniProt →

Function. May act as a transcriptional repressor.

Subunit / interactions. May interact with MVP.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in several fetal tissues, including gut, heart, brain, muscle, lung, testis and liver.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NDQ6-1	1	yes
Q8NDQ6-2	2
Q8NDQ6-4	4

RefSeq proteins (3): NP_001165696, NP_001165697, NP_689819 (=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
IPR050752	C2H2-ZF_domain	Family

Pfam: PF00096, PF01352, PF13912

UniProt features (26 total): zinc finger region 17, sequence variant 3, splice variant 2, chain 1, domain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDQ6-F1	75.35	0.36

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 (1): 109

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 72 (showing top): GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_REGULATION_OF_TRANSLATION, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN, GOMF_MRNA_REGULATORY_ELEMENT_BINDING_TRANSLATION_REPRESSOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, NCOA6_TARGET_GENES, PAX3_TARGET_GENES, RYBP_TARGET_GENES

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of translation (GO:0017148), negative regulation of DNA-templated transcription (GO:0045892), regulation of DNA-templated transcription (GO:0006355), negative regulation of gene expression (GO:0010629)

GO Molecular Function (7): mRNA regulatory element binding translation repressor activity (GO:0000900), 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 (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

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
cellular anatomical structure	3
regulation of DNA-templated transcription	2
DNA-templated transcription	2
regulation of gene expression	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
negative regulation of RNA biosynthetic process	1
regulation of RNA biosynthetic process	1
gene expression	1
negative regulation of macromolecule biosynthetic process	1
mRNA binding	1
translation repressor activity	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
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF540	FAM78A	Q5JUQ0	571
ZNF540	RIMS4	Q9H426	505
ZNF540	ALKAL1	Q6UXT8	479
ZNF540	PCDHAC1	Q9H158	475
ZNF540	MVP	Q14764	466
ZNF540	PRAC1	Q96KF2	449
ZNF540	KHDRBS2	Q5VWX1	447
ZNF540	NRIP2	Q9BQI9	418
ZNF540	WFDC6	Q9BQY6	399
ZNF540	GRM6	O15303	372
ZNF540	C12orf42	Q96LP6	367
ZNF540	SLC13A5	Q86YT5	356
ZNF540	TMEM179	Q6ZVK1	351
ZNF540	TIGD1	Q96MW7	349
ZNF540	CCDC30	Q5VVM6	322

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ZNF540	ECE1	psi-mi:“MI:0915”(physical association)	0.370
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): ZNF540 (Affinity Capture-MS), ZNF540 (Positive Genetic), ZNF540 (Affinity Capture-MS), ZNF540 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2RRD8, A6NHJ4, A6NK75, B4DU55, O75346, P0DPD5, P15621, P17030, P17039, P52737, Q0VGE8, Q14588, Q147U1, Q15928, Q2M3X9, Q3KNS6, Q494X3, Q4R6C2, Q5HYK9, Q5R5Q6, Q5R5S6, Q5REA0, Q5REK1, Q60585, Q61751, Q6ECI4, Q6P9Y7, Q6ZN19, Q6ZNA1, Q7Z3V5, Q86T29, Q86WZ6, Q8N141, Q8N7K0, Q8N9F8, Q8NA42, Q8NCK3, Q8NDQ6, Q8NEM1, Q8WV37

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	181
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1892 predictions. Top by Δscore:

Variant	Effect	Δscore
19:37551664:AGG:A	donor_loss	1.0000
19:37551666:GT:G	donor_loss	1.0000
19:37551667:T:G	donor_loss	1.0000
19:37583964:ATCTT:A	donor_loss	1.0000
19:37583966:CTTA:C	donor_loss	1.0000
19:37583967:TTACC:T	donor_loss	1.0000
19:37583968:TA:T	donor_loss	1.0000
19:37583969:A:AC	donor_gain	1.0000
19:37583969:AC:A	donor_gain	1.0000
19:37583970:C:CC	donor_gain	1.0000
19:37583970:CC:C	donor_gain	1.0000
19:37584095:CAA:C	acceptor_gain	1.0000
19:37586746:C:CC	acceptor_gain	1.0000
19:37598369:A:AG	acceptor_gain	1.0000
19:37598457:G:GG	donor_gain	1.0000
19:37611508:TTCA:T	acceptor_loss	1.0000
19:37611511:A:AC	acceptor_loss	1.0000
19:37611511:A:AG	acceptor_gain	1.0000
19:37611511:AG:A	acceptor_gain	1.0000
19:37611512:G:GG	acceptor_gain	1.0000
19:37611512:G:GT	acceptor_loss	1.0000
19:37611512:GG:G	acceptor_gain	1.0000
19:37611512:GGT:G	acceptor_gain	1.0000
19:37611512:GGTT:G	acceptor_gain	1.0000
19:37611512:GGTTT:G	acceptor_gain	1.0000
19:37551661:GCGAG:G	donor_gain	0.9900
19:37551663:GAG:G	donor_gain	0.9900
19:37551666:G:GG	donor_gain	0.9900
19:37566289:AGTCT:A	acceptor_loss	0.9900
19:37566290:GTC:G	acceptor_loss	0.9900

AlphaMissense

4418 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:37613042:T:C	F588L	0.997
19:37613044:T:A	F588L	0.997
19:37613044:T:G	F588L	0.997
19:37613126:T:C	F616L	0.997
19:37613128:T:A	F616L	0.997
19:37613128:T:G	F616L	0.997
19:37612622:T:C	F448L	0.996
19:37612624:T:A	F448L	0.996
19:37612624:T:G	F448L	0.996
19:37612538:T:C	F420L	0.994
19:37612540:T:A	F420L	0.994
19:37612540:T:G	F420L	0.994
19:37612874:T:C	F532L	0.994
19:37612876:T:A	F532L	0.994
19:37612876:T:G	F532L	0.994
19:37613210:T:C	F644L	0.994
19:37613212:T:A	F644L	0.994
19:37613212:T:G	F644L	0.994
19:37612454:T:C	F392L	0.993
19:37612456:T:A	F392L	0.993
19:37612456:T:G	F392L	0.993
19:37612958:T:C	F560L	0.993
19:37612960:T:A	F560L	0.993
19:37612960:T:G	F560L	0.993
19:37612479:G:C	R400P	0.992
19:37612790:T:C	F504L	0.992
19:37612792:T:A	F504L	0.992
19:37612792:T:G	F504L	0.992
19:37613073:A:C	Q598P	0.992
19:37612286:T:C	F336L	0.991

dbSNP variants (sampled 300 via entrez): RS1000033413 (19:37549428 T>G), RS1000104470 (19:37556768 G>A,T), RS1000105307 (19:37567646 G>T), RS1000112342 (19:37612782 G>A,C), RS1000136509 (19:37567366 C>T), RS1000367235 (19:37588246 T>A), RS1000381410 (19:37581350 C>G,T), RS1000398085 (19:37614657 A>C,G), RS1000410338 (19:37555193 T>G), RS1000412419 (19:37580952 C>T), RS1000497753 (19:37594309 G>A), RS1000569991 (19:37593994 C>A), RS1000580173 (19:37573617 A>G), RS1000729152 (19:37574168 T>A), RS1000732555 (19:37566219 C>T)

Disease associations

OMIM: gene MIM:613903 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_55	Refractive error	7.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
bisphenol S	decreases expression, decreases methylation	2
Nickel	decreases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
triphenyl phosphate	affects expression	1
butyraldehyde	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bromovanin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Hydralazine	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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