ZCCHC9

Summary

ZCCHC9 (zinc finger CCHC-type containing 9, HGNC:25424) is a protein-coding gene on chromosome 5q14.1, encoding Zinc finger CCHC domain-containing protein 9 (Q8N567). May down-regulate transcription mediated by NF-kappa-B and the serum response element. It is a selective cancer dependency (DepMap: 62.6% of cell lines).

Enables RNA binding activity. Located in nucleolus and nucleoplasm.

Source: NCBI Gene 84240 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 15 total
• Cancer dependency (DepMap): dependent in 62.6% of screened cell lines
• MANE Select transcript: NM_001131035

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25424
Approved symbol	ZCCHC9
Name	zinc finger CCHC-type containing 9
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761J139, PPP1R41
Ensembl gene	ENSG00000131732
Ensembl biotype	protein_coding
OMIM	620382
Entrez	84240

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000254037, ENST00000380199, ENST00000407610, ENST00000438268, ENST00000504502, ENST00000505860, ENST00000506458, ENST00000507402, ENST00000510227, ENST00000908072, ENST00000917107, ENST00000917108, ENST00000917109, ENST00000917110, ENST00000917111, ENST00000917112, ENST00000917113, ENST00000917114, ENST00000917115

RefSeq mRNA: 3 — MANE Select: NM_001131035 NM_001131035, NM_001131036, NM_032280

CCDS: CCDS4054

Canonical transcript exons

ENST00000407610 — 6 exons

Exon	Start	End
ENSE00001484089	81304741	81305141
ENSE00001484091	81301587	81301698
ENSE00001555873	81312544	81313297
ENSE00003560765	81308946	81309038
ENSE00003635258	81308561	81308711
ENSE00003658833	81311211	81311279

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 93.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.3465 / max 288.0773, expressed in 1804 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57345	10.8624	1771
57344	5.6909	1688
57346	4.4153	1584
57347	0.2616	112
57348	0.1163	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	93.41	gold quality
right lobe of liver	UBERON:0001114	91.17	gold quality
secondary oocyte	CL:0000655	90.91	gold quality
monocyte	CL:0000576	89.81	gold quality
leukocyte	CL:0000738	89.65	gold quality
upper arm skin	UBERON:0004263	89.18	silver quality
palpebral conjunctiva	UBERON:0001812	88.67	gold quality
tibia	UBERON:0000979	88.46	gold quality
smooth muscle tissue	UBERON:0001135	88.45	gold quality
gall bladder	UBERON:0002110	88.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.28	gold quality
lower esophagus	UBERON:0013473	88.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.24	gold quality
liver	UBERON:0002107	88.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.18	gold quality
vermiform appendix	UBERON:0001154	88.01	gold quality
adenohypophysis	UBERON:0002196	87.99	gold quality
stromal cell of endometrium	CL:0002255	87.94	gold quality
rectum	UBERON:0001052	87.93	gold quality
mucosa of transverse colon	UBERON:0004991	87.93	gold quality
adrenal tissue	UBERON:0018303	87.76	gold quality
esophagus	UBERON:0001043	87.72	gold quality
oocyte	CL:0000023	87.66	gold quality
body of uterus	UBERON:0009853	87.56	gold quality
left ovary	UBERON:0002119	87.51	gold quality
descending thoracic aorta	UBERON:0002345	87.51	gold quality
esophagus mucosa	UBERON:0002469	87.50	gold quality
islet of Langerhans	UBERON:0000006	87.49	gold quality
left coronary artery	UBERON:0001626	87.42	gold quality
ileal mucosa	UBERON:0000331	87.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

48 targeting ZCCHC9, 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-4500	99.99	72.72	2367
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-1303	99.65	69.77	1662

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 62.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Cytoplasmic ZCCHC9 could promote the proliferation and invasion of non-small cell lung cancer through the JNK pathway. (PMID:30644129)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zcchc9	ENSDARG00000007531
mus_musculus	Zcchc9	ENSMUSG00000021621
rattus_norvegicus	Zcchc9	ENSRNOG00000051682
caenorhabditis_elegans		WBGENE00017210

Paralogs (3): ZCCHC7 (ENSG00000147905), CNBP (ENSG00000169714), ZCCHC13 (ENSG00000187969)

Protein

Protein identifiers

Zinc finger CCHC domain-containing protein 9 — Q8N567 (reviewed: Q8N567)

All UniProt accessions (1): Q8N567

UniProt curated annotations — full annotation on UniProt →

Function. May down-regulate transcription mediated by NF-kappa-B and the serum response element.

Subcellular location. Nucleus. Nucleolus.

RefSeq proteins (3): NP_001124507, NP_001124508, NP_115656 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR042246	ZCCHC9	Family

Pfam: PF00098

UniProt features (8 total): zinc finger region 4, chain 1, region of interest 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N567-F1	69.70	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): 48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): PAX4_01, MARTINEZ_RB1_TARGETS_DN, INGRAM_SHH_TARGETS_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, ZHU_CMV_ALL_DN, ELK1_01, WHN_B, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_LIVER_CANCER_UP, NUYTTEN_EZH2_TARGETS_DN, LEE_RECENT_THYMIC_EMIGRANT, GOCC_NUCLEOLUS, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B, CCGNMNNTNACG_UNKNOWN

GO Biological Process (0):

GO Molecular Function (4): RNA binding (GO:0003723), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZCCHC9	ZCCHC7	Q8N3Z6	559
ZCCHC9	TMEM184C	Q9NVA4	476
ZCCHC9	SPTSSA	Q969W0	445
ZCCHC9	MPND	Q8N594	404
ZCCHC9	ZCCHC13	Q8WW36	397
ZCCHC9	TXK	P42681	396
ZCCHC9	C5orf15	Q8NC54	394
ZCCHC9	MANBAL	Q9NQG1	371
ZCCHC9	KIFC2	Q96AC6	369
ZCCHC9	PHYKPL	Q8IUZ5	368
ZCCHC9	CEACAM19	Q7Z692	356
ZCCHC9	NR2C1	P13056	348
ZCCHC9	MPHOSPH10	O00566	346
ZCCHC9	AMACR	Q9UHK6	346
ZCCHC9	TMEM14A	Q9Y6G1	342

IntAct

81 interactions, top by confidence:

A	B	Type	Score
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ZNF689	ZNF593	psi-mi:“MI:0914”(association)	0.530
NIFK	RSL1D1	psi-mi:“MI:0914”(association)	0.530
SURF2	HEXIM1	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZCCHC9	RPS3A	psi-mi:“MI:0914”(association)	0.530
RPS3A	CBX6	psi-mi:“MI:0914”(association)	0.530
REXO4	CASC3	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
PPP1CA	ZCCHC9	psi-mi:“MI:0407”(direct interaction)	0.440
Ppp2ca	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
FBXO31	CCNQ	psi-mi:“MI:0914”(association)	0.350
k8	RGL2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SURF2	KPNA6	psi-mi:“MI:0914”(association)	0.350
ZC3H3	ANKHD1	psi-mi:“MI:0914”(association)	0.350
GPATCH4	NOP56	psi-mi:“MI:0914”(association)	0.350

BioGRID (98): ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS), ZCCHC9 (Affinity Capture-MS)

ESM2 similar proteins: A3N0X3, A5DEY7, A6VLB1, A7YY07, A8WXX7, A9LMC0, B0BPQ7, B8BDW1, B8BJV8, E9Q8D0, O59800, P40507, P58269, P58270, P91599, P92186, Q0II91, Q12476, Q16U25, Q18691, Q26891, Q299F9, Q2HJG4, Q2VPH1, Q5F1R6, Q5ZMS6, Q61103, Q61712, Q61CX7, Q65W23, Q69JZ7, Q69ZW3, Q6C3L4, Q6FSQ0, Q6PGY5, Q6Q152, Q7PYQ5, Q8H110, Q8N567, Q8R1J3

Diamond homologs: Q8N567, Q8R1J3, Q9HFF2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
Eukaryotic Translation Initiation	5	32.1×	5e-06
Cap-dependent Translation Initiation	5	32.1×	5e-06
SARS-CoV-1 modulates host translation machinery	5	32.1×	5e-06
Nonsense-Mediated Decay (NMD)	6	29.1×	2e-06
Eukaryotic Translation Elongation	5	29.0×	8e-06
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	28.3×	9e-06
rRNA processing in the nucleus and cytosol	7	23.5×	2e-06
rRNA modification in the nucleus and cytosol	6	23.4×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	10	29.6×	5e-10
rRNA processing	11	20.2×	1e-09
cytoplasmic translation	7	16.8×	3e-05
translation	8	10.7×	7e-05
nucleosome assembly	5	9.1×	1e-02
RNA splicing	6	6.9×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

916 predictions. Top by Δscore:

Variant	Effect	Δscore
5:81308556:CCTA:C	acceptor_loss	1.0000
5:81308558:TA:T	acceptor_loss	1.0000
5:81308559:A:AC	acceptor_loss	1.0000
5:81308560:G:GA	acceptor_loss	1.0000
5:81308560:GGT:G	acceptor_gain	1.0000
5:81308560:GGTGT:G	acceptor_gain	1.0000
5:81308683:GT:G	donor_gain	1.0000
5:81308943:CAG:C	acceptor_loss	1.0000
5:81308944:A:AG	acceptor_gain	1.0000
5:81308944:AGGC:A	acceptor_gain	1.0000
5:81308944:AGGCG:A	acceptor_loss	1.0000
5:81308945:G:GA	acceptor_gain	1.0000
5:81308945:GGC:G	acceptor_gain	1.0000
5:81308945:GGCG:G	acceptor_gain	1.0000
5:81308945:GGCGA:G	acceptor_gain	1.0000
5:81309035:GATG:G	donor_gain	1.0000
5:81309039:G:GG	donor_gain	1.0000
5:81309041:AA:A	donor_loss	1.0000
5:81308690:GC:G	donor_gain	0.9900
5:81308709:TTG:T	donor_loss	0.9900
5:81308710:TGGTA:T	donor_loss	0.9900
5:81308711:GGTA:G	donor_loss	0.9900
5:81308712:GTATG:G	donor_loss	0.9900
5:81308713:T:TC	donor_loss	0.9900
5:81308942:A:AG	acceptor_gain	0.9900
5:81308944:AG:A	acceptor_gain	0.9900
5:81308945:GG:G	acceptor_gain	0.9900
5:81309034:TGATG:T	donor_gain	0.9900
5:81309035:GATGG:G	donor_gain	0.9900
5:81309036:ATG:A	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015022 (5:81301671 G>A,T), RS1000331796 (5:81309861 C>A,G,T), RS1000472780 (5:81301553 C>A,G,T), RS1000839735 (5:81308186 GAC>G), RS1000908402 (5:81307795 G>A), RS1001052534 (5:81301508 A>G), RS1001128995 (5:81308079 G>A,C), RS1001745473 (5:81302835 G>A), RS1001866760 (5:81300259 C>G,T), RS1002093050 (5:81303164 G>A), RS1002331969 (5:81306676 A>G), RS1002479198 (5:81304277 T>A), RS1002847998 (5:81311330 C>T), RS1002900258 (5:81310932 A>G), RS1002934967 (5:81304968 G>A)

Disease associations

OMIM: gene MIM:620382 | 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

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	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
Air Pollutants	increases abundance, decreases expression	1
Arsenic	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Gold	decreases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	increases abundance, increases expression	1
Nicotine	increases expression	1
Phthalic Acids	increases methylation	1
Potassium Chloride	decreases expression, decreases response to substance	1
Ribonucleotides	affects binding	1
Dronabinol	decreases expression, decreases response to substance	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation, increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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