ZNF546

Summary

ZNF546 (zinc finger protein 546, HGNC:28671) is a protein-coding gene on chromosome 19q13.2, encoding Zinc finger protein 546 (Q86UE3). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in membrane. Predicted to be active in nucleus.

Source: NCBI Gene 339327 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_178544

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28671
Approved symbol	ZNF546
Name	zinc finger protein 546
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC43537
Ensembl gene	ENSG00000187187
Ensembl biotype	protein_coding
Entrez	339327

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000347077, ENST00000593687, ENST00000595225, ENST00000596894, ENST00000597363, ENST00000599504, ENST00000600094, ENST00000601138, ENST00000602253, ENST00000651981, ENST00000951738

RefSeq mRNA: 2 — MANE Select: NM_178544 NM_001297763, NM_178544

CCDS: CCDS12548, CCDS77297

Canonical transcript exons

ENST00000347077 — 7 exons

Exon	Start	End
ENSE00001338702	39998248	39998410
ENSE00001414802	39997861	39997915
ENSE00001432294	40013665	40021038
ENSE00002506963	40007274	40007400
ENSE00002522561	40008470	40008565
ENSE00003036812	39997060	39997157
ENSE00003563175	40006096	40006182

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 87.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.4641 / max 39.6955, expressed in 1053 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175811	2.0975	916
175812	0.3666	150

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	87.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.04	gold quality
right testis	UBERON:0004534	83.23	gold quality
left testis	UBERON:0004533	82.58	gold quality
calcaneal tendon	UBERON:0003701	82.31	gold quality
testis	UBERON:0000473	82.18	gold quality
adrenal tissue	UBERON:0018303	79.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.10	gold quality
endometrium	UBERON:0001295	76.89	gold quality
cerebellar hemisphere	UBERON:0002245	75.70	gold quality
cerebellar cortex	UBERON:0002129	75.64	gold quality
cerebellum	UBERON:0002037	75.49	gold quality
skeletal muscle tissue	UBERON:0001134	75.42	gold quality
apex of heart	UBERON:0002098	75.26	gold quality
muscle tissue	UBERON:0002385	75.21	gold quality
smooth muscle tissue	UBERON:0001135	74.89	gold quality
ovary	UBERON:0000992	74.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.74	gold quality
left ovary	UBERON:0002119	74.68	gold quality
muscle of leg	UBERON:0001383	74.46	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.37	gold quality
right adrenal gland	UBERON:0001233	74.32	gold quality
right ovary	UBERON:0002118	74.23	gold quality
gastrocnemius	UBERON:0001388	74.21	gold quality
nucleus accumbens	UBERON:0001882	73.87	gold quality
adrenal gland	UBERON:0002369	73.86	gold quality
right uterine tube	UBERON:0001302	73.71	gold quality
left adrenal gland cortex	UBERON:0035825	73.42	gold quality
right adrenal gland cortex	UBERON:0035827	73.36	gold quality
left adrenal gland	UBERON:0001234	73.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

160 targeting ZNF546, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872

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 546 — Q86UE3 (reviewed: Q86UE3)

Alternative names: Zinc finger protein 49

All UniProt accessions (7): A0A494C1I4, Q86UE3, M0QXH5, M0QXR6, M0QY24, M0QZB2, M0R292

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 (2): NP_001284692, NP_848639* (*=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 (33 total): zinc finger region 22, sequence variant 8, chain 1, domain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UE3-F1	73.95	0.04

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): 179

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 79 (showing top): GGAMTNNNNNTCCY_UNKNOWN, KUUSELO_PANCREATIC_CANCER_19Q13_AMPLIFICATION, STAT1_02, YKACATTT_UNKNOWN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, STAT1_03, SNACANNNYSYAGA_UNKNOWN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, DIDO1_TARGET_GENES, FEV_TARGET_GENES, NFE2L1_TARGET_GENES, NKX2_3_TARGET_GENES, TEAD2_TARGET_GENES, ZBTB12_TARGET_GENES, ZNF223_TARGET_GENES

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), 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 (2): nucleus (GO:0005634), membrane (GO:0016020)

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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription	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
cellular anatomical structure	1

Protein interactions and networks

STRING

374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF546	ZNF438	Q7Z4V0	552
ZNF546	OR8D2	Q9GZM6	488
ZNF546	KRT83	P78385	450
ZNF546	OR2M7	Q8NG81	438
ZNF546	TRAT1	Q6PIZ9	429
ZNF546	C19orf47	Q8N9M1	419
ZNF546	SULT1C3	Q6IMI6	413
ZNF546	MTA1	Q13330	401
ZNF546	ACTMAP	Q5BKX5	400
ZNF546	NKAPL	Q5M9Q1	399
ZNF546	OR10C1	Q96KK4	396
ZNF546	ADD1	P35611	390
ZNF546	KRT3	P12035	375
ZNF546	LRRC66	Q68CR7	375
ZNF546	MAP4	P27816	363

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CBX4		psi-mi:“MI:0914”(association)	0.350
ZNF546	CALU	psi-mi:“MI:0914”(association)	0.350
EPHA1	ZNF546	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): ZNF546 (Affinity Capture-MS), ZNF546 (Proximity Label-MS), ZNF546 (Affinity Capture-RNA)

ESM2 similar proteins: A2VDQ7, A6NNF4, A8MQ14, A8MTY0, E9QAG8, O75290, O75373, P08043, P0CJ79, P10751, P17017, P17027, P17039, P35789, P51522, P51523, Q08AN1, Q14585, Q14587, Q3SYV7, Q3ZCX4, Q4R4C7, Q52M93, Q5MCW4, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6ECI4, Q6JLC9, Q6P3V2, Q6P5C7, Q6ZN57, Q86UE3, Q86XN6, Q86YE8, Q8C827, Q8IYB9, Q8N4W9, Q8N7M2

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1101 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40006094:A:AG	acceptor_gain	1.0000
19:40006095:G:GG	acceptor_gain	1.0000
19:40006095:GCCCC:G	acceptor_gain	1.0000
19:40007399:GG:G	donor_gain	1.0000
19:40007400:GG:G	donor_gain	1.0000
19:40007401:G:GC	donor_loss	1.0000
19:40007401:G:GG	donor_gain	1.0000
19:40008463:T:G	acceptor_gain	1.0000
19:39997843:T:TA	acceptor_gain	0.9900
19:40006094:AGC:A	acceptor_loss	0.9900
19:40006095:GC:G	acceptor_gain	0.9900
19:40006181:AT:A	donor_gain	0.9900
19:40006183:G:GG	donor_gain	0.9900
19:40008468:AG:A	acceptor_gain	0.9900
19:40008469:GG:G	acceptor_gain	0.9900
19:40008469:GGAT:G	acceptor_gain	0.9900
19:39997839:ATTCT:A	acceptor_gain	0.9800
19:40006095:GCC:G	acceptor_gain	0.9800
19:40008462:A:AG	acceptor_gain	0.9800
19:40008462:AT:A	acceptor_gain	0.9800
19:40008463:T:TA	acceptor_gain	0.9800
19:40008464:GAGCA:G	acceptor_loss	0.9800
19:40008467:CAGGA:C	acceptor_loss	0.9800
19:40008468:AGG:A	acceptor_loss	0.9800
19:40008469:G:T	acceptor_loss	0.9800
19:40008561:CACAG:C	donor_loss	0.9800
19:40008562:ACAG:A	donor_loss	0.9800
19:40008563:CAGGT:C	donor_loss	0.9800
19:40008564:AG:A	donor_loss	0.9800
19:40008565:GG:G	donor_loss	0.9800

AlphaMissense

5599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40014450:T:C	F394L	0.997
19:40014452:T:A	F394L	0.997
19:40014452:T:G	F394L	0.997
19:40014702:T:C	F478L	0.997
19:40014704:T:A	F478L	0.997
19:40014704:T:G	F478L	0.997
19:40014198:T:C	F310L	0.996
19:40014200:T:A	F310L	0.996
19:40014200:T:G	F310L	0.996
19:40014618:T:C	F450L	0.996
19:40014620:T:A	F450L	0.996
19:40014620:T:G	F450L	0.996
19:40015122:T:C	F618L	0.996
19:40015124:T:A	F618L	0.996
19:40015124:T:G	F618L	0.996
19:40015206:T:C	F646L	0.996
19:40015208:T:A	F646L	0.996
19:40015208:T:G	F646L	0.996
19:40014282:T:C	F338L	0.995
19:40014284:T:A	F338L	0.995
19:40014284:T:G	F338L	0.995
19:40014870:T:C	F534L	0.995
19:40014872:T:A	F534L	0.995
19:40014872:T:G	F534L	0.995
19:40014030:T:C	F254L	0.994
19:40014032:T:A	F254L	0.994
19:40014032:T:G	F254L	0.994
19:40014114:T:C	F282L	0.994
19:40014116:T:A	F282L	0.994
19:40014116:T:G	F282L	0.994

dbSNP variants (sampled 300 via entrez): RS1000019536 (19:40005974 T>C,G), RS1000025413 (19:40001688 T>G), RS1000056404 (19:40000416 A>G), RS1000125072 (19:40000804 C>G,T), RS1000308853 (19:40007543 T>G), RS1000346726 (19:40008267 G>A), RS1000641283 (19:39995690 G>A,C,T), RS1000649454 (19:39996361 G>C), RS1000914246 (19:40009252 G>A), RS1000918694 (19:40016348 C>T), RS1000972580 (19:39995441 G>A), RS1001052638 (19:40015407 A>C,G), RS1001261469 (19:40009574 T>C), RS1001390695 (19:40016708 C>T), RS1001441617 (19:40016389 G>A)

Disease associations

OMIM: gene `` | 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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	2
Particulate Matter	increases abundance, increases expression	2
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
2-palmitoylglycerol	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Folic Acid	decreases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Rifampin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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