ZC3H10

Summary

ZC3H10 (zinc finger CCCH-type containing 10, HGNC:25893) is a protein-coding gene on chromosome 12q13.2, encoding Zinc finger CCCH domain-containing protein 10 (Q96K80). Specific regulator of miRNA biogenesis. It is a selective cancer dependency (DepMap: 11.7% of cell lines).

Enables miRNA binding activity. Involved in negative regulation of miRNA processing. Acts upstream of with a positive effect on post-transcriptional regulation of gene expression. Located in nucleus.

Source: NCBI Gene 84872 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 47 total
• Cancer dependency (DepMap): dependent in 11.7% of screened cell lines
• MANE Select transcript: NM_032786

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25893
Approved symbol	ZC3H10
Name	zinc finger CCCH-type containing 10
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14451
Ensembl gene	ENSG00000135482
Ensembl biotype	protein_coding
Entrez	84872

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000257940, ENST00000546903, ENST00000549973, ENST00000551880, ENST00000552345, ENST00000880504, ENST00000931935, ENST00000931936

RefSeq mRNA: 3 — MANE Select: NM_032786 NM_001303124, NM_001303125, NM_032786

CCDS: CCDS8903

Canonical transcript exons

ENST00000257940 — 3 exons

Exon	Start	End
ENSE00001300066	56120511	56127514
ENSE00002375723	56118266	56118318
ENSE00003619010	56119088	56119151

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 84.05.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7251 / max 26.0996, expressed in 248 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126065	8.8941	1775
126066	0.3807	150
126067	0.3444	138

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	84.05	gold quality
pancreatic ductal cell	CL:0002079	83.69	silver quality
endothelial cell	CL:0000115	82.53	silver quality
tibialis anterior	UBERON:0001385	81.45	silver quality
left ventricle myocardium	UBERON:0006566	81.05	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.95	gold quality
epithelial cell of pancreas	CL:0000083	80.41	gold quality
upper arm skin	UBERON:0004263	80.22	gold quality
buccal mucosa cell	CL:0002336	79.13	gold quality
cerebellar vermis	UBERON:0004720	78.88	gold quality
ileal mucosa	UBERON:0000331	78.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.77	gold quality
kidney epithelium	UBERON:0004819	77.72	gold quality
deltoid	UBERON:0001476	77.00	silver quality
nipple	UBERON:0002030	76.04	gold quality
stromal cell of endometrium	CL:0002255	75.52	gold quality
granulocyte	CL:0000094	74.71	gold quality
saphenous vein	UBERON:0007318	74.71	gold quality
pericardium	UBERON:0002407	74.42	silver quality
left testis	UBERON:0004533	74.37	gold quality
right testis	UBERON:0004534	74.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.22	gold quality
blood	UBERON:0000178	73.99	gold quality
muscle of leg	UBERON:0001383	73.99	gold quality
testis	UBERON:0000473	73.95	gold quality
gastrocnemius	UBERON:0001388	73.86	gold quality
skeletal muscle organ	UBERON:0014892	73.83	gold quality
pons	UBERON:0000988	73.74	silver quality
popliteal artery	UBERON:0002250	73.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting ZC3H10, 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-9-5P	100.00	72.28	2361
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-11399	98.71	65.69	869

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• ZC3H10 inhibits the anchorage independent growth of tumor cells, which is consistent with a tumor suppressor function. (PMID:18814840)
• our study identifies Zc3h10 as a novel mitochondrial regulator. (PMID:29507079)
• Zc3h10 Acts as a Transcription Factor and Is Phosphorylated to Activate the Thermogenic Program. (PMID:31775033)
• A HOTAIR regulatory element modulates glioma cell sensitivity to temozolomide through long-range regulation of multiple target genes. (PMID:31953347)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zc3h10	ENSDARG00000030335
mus_musculus	Zc3h10	ENSMUSG00000039810
rattus_norvegicus	Zc3h10	ENSRNOG00000040281
caenorhabditis_elegans		WBGENE00021816

Paralogs (3): MBNL3 (ENSG00000076770), MBNL2 (ENSG00000139793), MBNL1 (ENSG00000152601)

Protein

Protein identifiers

Zinc finger CCCH domain-containing protein 10 — Q96K80 (reviewed: Q96K80)

All UniProt accessions (4): F8VQT2, F8VSG0, F8VYY3, Q96K80

UniProt curated annotations — full annotation on UniProt →

Function. Specific regulator of miRNA biogenesis. Binds, via the C3H1-type zinc finger domains, to the binding motif 5’-GCAGCGC-3’ on microRNA pri-MIR143 and negatively regulates the processing to mature microRNA.

Subcellular location. Nucleus.

RefSeq proteins (3): NP_001290053, NP_001290054, NP_116175* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain

Pfam: PF00642, PF14608

UniProt features (17 total): compositionally biased region 4, zinc finger region 3, mutagenesis site 3, region of interest 3, modified residue 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96K80-F1	60.31	0.09

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 (2): 185, 186

Mutagenesis-validated functional residues (3):

Position	Phenotype
50–56	abolishes binding to pri-mir143.
87–92	abolishes binding to pri-mir143.
148–154	reduces binding to pri-mir143.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): GGGACCA_MIR133A_MIR133B, AREB6_01, CREBP1_Q2, AP2_Q3, CREB_Q4, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, YGACNNYACAR_UNKNOWN, FREAC3_01, MYCMAX_01, WCTCNATGGY_UNKNOWN, E4F1_Q6, GOBP_RNA_SPLICING, TATA_C, RYTTCCTG_ETS2_B, WHN_B

GO Biological Process (3): post-transcriptional regulation of gene expression (GO:0010608), regulation of RNA splicing (GO:0043484), negative regulation of miRNA processing (GO:1903799)

GO Molecular Function (5): RNA binding (GO:0003723), zinc ion binding (GO:0008270), miRNA binding (GO:0035198), 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
regulation of gene expression	2
RNA splicing	1
regulation of primary metabolic process	1
negative regulation of gene expression	1
miRNA processing	1
negative regulation of miRNA-mediated gene silencing	1
regulation of miRNA processing	1
nucleic acid binding	1
transition metal ion binding	1
regulatory RNA binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

734 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZC3H10	TMEM69	Q5SWH9	601
ZC3H10	CCDC137	Q6PK04	562
ZC3H10	CLEC19A	Q6UXS0	559
ZC3H10	CBLN3	Q6UW01	533
ZC3H10	LAMB4	A4D0S4	517
ZC3H10	PLTP	P55058	509
ZC3H10	ESYT1	Q9BSJ8	472
ZC3H10	PECR	Q9BY49	471
ZC3H10	BCDIN3D	Q7Z5W3	456
ZC3H10	ZCRB1	Q8TBF4	424
ZC3H10	CLUH	O75153	389
ZC3H10	CALCOCO1	Q9P1Z2	371
ZC3H10	RBM27	Q9P2N5	364
ZC3H10	ZC3H6	P61129	363
ZC3H10	C1QTNF7	Q9BXJ2	363

IntAct

184 interactions, top by confidence:

A	B	Type	Score
ATXN1	ZC3H10	psi-mi:“MI:0915”(physical association)	0.760
ZC3H10	ATXN1	psi-mi:“MI:0915”(physical association)	0.760
ZC3H10	DAZAP2	psi-mi:“MI:0915”(physical association)	0.700
DAZAP2	ZC3H10	psi-mi:“MI:0915”(physical association)	0.700
ZC3H10	RBPMS	psi-mi:“MI:0915”(physical association)	0.670
RBPMS	ZC3H10	psi-mi:“MI:0915”(physical association)	0.670
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
RPL7A	NOP56	psi-mi:“MI:0914”(association)	0.640
ZC3H10	DAB1	psi-mi:“MI:0915”(physical association)	0.560
ZC3H10	PRR20C	psi-mi:“MI:0915”(physical association)	0.560
APPBP2	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560
PRR20C	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560
DAB1	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560
ZC3H10	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
ZC3H10	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
FOSB	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560
PRR20D	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560
RBPMS2	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560
BOLL	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560
STAM2	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (219): ZC3H10 (Two-hybrid), ZC3H10 (Two-hybrid), ZC3H10 (Two-hybrid), ZC3H10 (Two-hybrid), PRR20A (Two-hybrid), ZC3H10 (Affinity Capture-MS), ZC3H10 (Two-hybrid), ZC3H10 (Two-hybrid), ZC3H10 (Synthetic Lethality), ZC3H10 (Two-hybrid), ZC3H10 (Affinity Capture-MS), ZC3H10 (Affinity Capture-MS), ZC3H10 (Affinity Capture-MS), ZC3H10 (Affinity Capture-MS), ZC3H10 (Two-hybrid)

ESM2 similar proteins: A0A8I6B1J2, A0AV96, A8XND8, B3M3R5, B3NGA1, B4HUE4, B4IX08, B4KX02, B4LFQ9, B4MM23, B4PIS2, B4QRJ0, F2Z3T4, G5EFF1, O01367, P16914, P31367, Q0V9L3, Q24312, Q32NN2, Q56V19, Q5R4F5, Q5R5P4, Q5VZF2, Q5W9D5, Q5W9D6, Q5W9D7, Q5ZKW9, Q66H68, Q6IRN2, Q6P0D0, Q6P104, Q6Q2B2, Q7JJZ8, Q7TSY6, Q8C181, Q8MSV2, Q8R003, Q8R205, Q91WT8

Diamond homologs: Q6K977, Q8R205, Q96K80

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	13	30.0×	1e-14
Viral mRNA Translation	13	30.0×	1e-14
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	13	29.7×	1e-14
Selenocysteine synthesis	13	28.4×	1e-14
Eukaryotic Translation Termination	13	28.4×	1e-14
Response of EIF2AK4 (GCN2) to amino acid deficiency	14	28.2×	4e-15
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	13	27.8×	1e-14
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	13	27.8×	1e-14

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	13	29.7×	2e-13
ribosomal small subunit biogenesis	6	16.9×	2e-04
translation	13	16.5×	2e-10
rRNA processing	8	14.0×	1e-05
RNA processing	5	13.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

467 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56120509:A:AG	acceptor_gain	1.0000
12:56120509:AGT:A	acceptor_gain	1.0000
12:56120510:G:GG	acceptor_gain	1.0000
12:56120510:GT:G	acceptor_gain	1.0000
12:56120510:GTG:G	acceptor_gain	1.0000
12:56118316:C:T	donor_gain	0.9900
12:56118317:AGG:A	donor_loss	0.9900
12:56118318:GG:G	donor_loss	0.9900
12:56118319:G:GA	donor_loss	0.9900
12:56118320:T:G	donor_loss	0.9900
12:56119081:T:A	acceptor_gain	0.9900
12:56119148:TCAGG:T	donor_loss	0.9900
12:56119149:CAG:C	donor_loss	0.9900
12:56119150:AGGT:A	donor_loss	0.9900
12:56119151:GGTAT:G	donor_loss	0.9900
12:56119152:GTATC:G	donor_loss	0.9900
12:56119153:T:G	donor_loss	0.9900
12:56119083:CTCA:C	acceptor_loss	0.9800
12:56119084:TCA:T	acceptor_loss	0.9800
12:56119086:A:AG	acceptor_gain	0.9800
12:56119086:A:AT	acceptor_loss	0.9800
12:56119087:G:GG	acceptor_gain	0.9800
12:56120505:TTGTA:T	acceptor_loss	0.9800
12:56120506:TGTA:T	acceptor_loss	0.9800
12:56120507:GTA:G	acceptor_loss	0.9800
12:56120508:TA:T	acceptor_loss	0.9800
12:56120509:A:AC	acceptor_loss	0.9800
12:56120510:G:GT	acceptor_loss	0.9800
12:56120510:GTGGT:G	acceptor_gain	0.9700
12:56119087:GA:G	acceptor_gain	0.9600

AlphaMissense

2808 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56120686:T:A	C42S	1.000
12:56120686:T:C	C42R	1.000
12:56120687:G:A	C42Y	1.000
12:56120687:G:C	C42S	1.000
12:56120688:T:G	C42W	1.000
12:56120692:G:C	D44H	1.000
12:56120693:A:C	D44A	1.000
12:56120693:A:G	D44G	1.000
12:56120693:A:T	D44V	1.000
12:56120695:T:C	F45L	1.000
12:56120697:C:A	F45L	1.000
12:56120697:C:G	F45L	1.000
12:56120702:G:C	R47T	1.000
12:56120702:G:T	R47M	1.000
12:56120703:G:C	R47S	1.000
12:56120703:G:T	R47S	1.000
12:56120710:T:A	C50S	1.000
12:56120710:T:C	C50R	1.000
12:56120711:G:A	C50Y	1.000
12:56120711:G:C	C50S	1.000
12:56120711:G:T	C50F	1.000
12:56120712:C:G	C50W	1.000
12:56120728:T:A	C56S	1.000
12:56120728:T:C	C56R	1.000
12:56120729:G:A	C56Y	1.000
12:56120729:G:C	C56S	1.000
12:56120729:G:T	C56F	1.000
12:56120730:C:G	C56W	1.000
12:56120740:C:A	H60N	1.000
12:56120740:C:G	H60D	1.000

dbSNP variants (sampled 300 via entrez): RS1000598312 (12:56121174 G>A), RS1000699052 (12:56127192 G>A,T), RS1000793408 (12:56127518 T>A), RS1000910271 (12:56125231 TAAC>T), RS1001181999 (12:56118101 T>C,G), RS1001552584 (12:56120297 C>T), RS1001570377 (12:56126258 T>A), RS1001680451 (12:56124686 A>G), RS1001692193 (12:56117959 T>C), RS1001753935 (12:56124471 G>A), RS1001936374 (12:56126715 C>G), RS1002295197 (12:56119025 C>T), RS1003184641 (12:56121113 G>A), RS1003207511 (12:56125412 G>A,T), RS1003644646 (12:56125110 A>C)

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

4 associations (top):

Study	Trait	p-value
GCST004367_1	Anorexia nervosa	4.000000e-09
GCST007563_23	Allergic disease (asthma, hay fever or eczema)	4.000000e-10
GCST007564_9	Asthma or allergic disease (pleiotropy)	1.000000e-13
GCST008916_124	Asthma	1.000000e-16

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
OTX015	increases expression	1
mivebresib	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	increases abundance, decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Potassium Chloride	decreases expression, decreases response to substance	1
Ribonucleotides	affects binding	1
Dronabinol	decreases expression, decreases response to substance	1
Urethane	affects expression	1

Clinical trials (associated diseases)

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