ZCCHC3

Summary

ZCCHC3 (zinc finger CCHC-type containing 3, HGNC:16230) is a protein-coding gene on chromosome 20p13, encoding Zinc finger CCHC domain-containing protein 3 (Q9NUD5). Nucleic acid-binding protein involved in innate immune response to DNA and RNA viruses.

Enables double-stranded DNA binding activity. Involved in cellular response to exogenous dsRNA; detection of virus; and positive regulation of innate immune response. Located in cytoplasm.

Source: NCBI Gene 85364 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_033089

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16230
Approved symbol	ZCCHC3
Name	zinc finger CCHC-type containing 3
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	dJ1103G7.7
Ensembl gene	ENSG00000247315
Ensembl biotype	protein_coding
OMIM	618326
Entrez	85364

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000500893

RefSeq mRNA: 1 — MANE Select: NM_033089 NM_033089

CCDS: CCDS42844

Canonical transcript exons

ENST00000500893 — 1 exons

Exon	Start	End
ENSE00001977652	297570	300321

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 91.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5176 / max 208.2473, expressed in 1762 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183001	9.1469	1742
182999	0.7009	425
183002	0.4421	209
183000	0.2277	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	91.73	gold quality
ventricular zone	UBERON:0003053	91.72	gold quality
tibialis anterior	UBERON:0001385	90.95	gold quality
oocyte	CL:0000023	90.55	gold quality
ganglionic eminence	UBERON:0004023	90.10	gold quality
secondary oocyte	CL:0000655	89.51	gold quality
pancreatic ductal cell	CL:0002079	88.63	silver quality
granulocyte	CL:0000094	88.36	gold quality
cortical plate	UBERON:0005343	87.11	gold quality
kidney epithelium	UBERON:0004819	86.06	silver quality
placenta	UBERON:0001987	84.79	gold quality
lymph node	UBERON:0000029	84.76	gold quality
deltoid	UBERON:0001476	84.66	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.34	gold quality
leukocyte	CL:0000738	84.20	gold quality
adrenal tissue	UBERON:0018303	84.09	gold quality
left ventricle myocardium	UBERON:0006566	83.91	silver quality
monocyte	CL:0000576	83.76	gold quality
spleen	UBERON:0002106	83.64	gold quality
lower lobe of lung	UBERON:0008949	82.97	gold quality
metanephros	UBERON:0000081	82.90	gold quality
hypothalamus	UBERON:0001898	82.77	gold quality
parotid gland	UBERON:0001831	82.59	gold quality
ovary	UBERON:0000992	82.31	gold quality
bone marrow cell	CL:0002092	82.30	gold quality
mucosa of transverse colon	UBERON:0004991	82.28	gold quality
apex of heart	UBERON:0002098	82.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.12	gold quality
cerebellar vermis	UBERON:0004720	82.11	silver quality
epithelium of mammary gland	UBERON:0003244	82.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting ZCCHC3, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-627-3P	99.90	71.42	3316

Literature-anchored findings (GeneRIF, showing 1)

• Proteomic analysis reveals zinc-finger CCHC-type containing protein 3 as a factor inhibiting virus infection by promoting innate signaling. (PMID:35872280)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zcchc3	ENSMUSG00000074682
rattus_norvegicus	Zcchc3	ENSRNOG00000068900

Protein

Protein identifiers

Zinc finger CCHC domain-containing protein 3 — Q9NUD5 (reviewed: Q9NUD5)

All UniProt accessions (1): Q9NUD5

UniProt curated annotations — full annotation on UniProt →

Function. Nucleic acid-binding protein involved in innate immune response to DNA and RNA viruses. Binds DNA and RNA in the cytoplasm and acts by promoting recognition of viral nucleic acids by virus sensors, such as RIGI, IFIH1/MDA5 and CGAS. Acts as a co-sensor for recognition of double-stranded DNA (dsDNA) by cGAS in the cytoplasm, thereby playing a role in innate immune response to cytosolic dsDNA and DNA virus. Binds dsDNA and probably acts by promoting sensing of dsDNA by CGAS, leading to enhance CGAS oligomerization and activation. Promotes sensing of viral RNA by RIGI-like receptors proteins RIGI and IFIH1/MDA5 via two mechanisms: binds double-stranded RNA (dsRNA), enhancing the binding of RIGI and IFIH1/MDA5 to dsRNA and promotes ‘Lys-63’-linked ubiquitination and subsequent activation of RIGI and IFIH1/MDA5.

Subunit / interactions. Interacts with CGAS. Interacts with RIGI. Interacts with IFIH1/MDA5.

Subcellular location. Cytoplasm.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NUD5-1	1	yes
Q9NUD5-2	2

RefSeq proteins (1): NP_149080* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR042509	ZCCHC3	Family
IPR057810	RBD_ZCCHC3_1st	Domain
IPR057811	RBD_ZCCHC3_2nd	Domain

Pfam: PF00098, PF23057, PF23058

UniProt features (13 total): compositionally biased region 5, zinc finger region 3, chain 1, modified residue 1, splice variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUD5-F1	67.38	0.27

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): 201

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, ACTACCT_MIR196A_MIR196B, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, CHANDRAN_METASTASIS_DN, TTGGGAG_MIR150, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, NF1_Q6_01, GOBP_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (8): activation of innate immune response (GO:0002218), detection of virus (GO:0009597), positive regulation of type I interferon production (GO:0032481), innate immune response (GO:0045087), defense response to virus (GO:0051607), cellular response to exogenous dsRNA (GO:0071360), positive regulation of RIG-I signaling pathway (GO:1900246), immune system process (GO:0002376)

GO Molecular Function (7): double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to virus	2
nucleic acid binding	2
binding	2
activation of immune response	1
positive regulation of innate immune response	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
immune response	1
defense response to symbiont	1
defense response	1
response to exogenous dsRNA	1
cellular response to dsRNA	1
RIG-I signaling pathway	1
regulation of RIG-I signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
biological_process	1
DNA binding	1
transition metal ion binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZCCHC3	CGAS	Q8N884	681
ZCCHC3	IFIH1	Q9BYX4	678
ZCCHC3	RIGI	O95786	607
ZCCHC3	MOV10	Q9HCE1	605
ZCCHC3	TRIM38	O00635	549
ZCCHC3	UPF1	Q92900	544
ZCCHC3	TRIM4	Q9C037	506
ZCCHC3	PABPC4	Q13310	488
ZCCHC3	PABPC1	P11940	487
ZCCHC3	PQBP1	O60828	485
ZCCHC3	GAREM1	Q9H706	470
ZCCHC3	SPATA4	Q8NEY3	457
ZCCHC3	AGPAT5	Q9NUQ2	434
ZCCHC3	TFAP2D	Q7Z6R9	433
ZCCHC3	G3BP1	Q13283	420

IntAct

172 interactions, top by confidence:

A	B	Type	Score
RACK1	HELZ	psi-mi:“MI:0914”(association)	0.770
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
FAM120A	SYNCRIP	psi-mi:“MI:0914”(association)	0.640
RACK1	RIOK3	psi-mi:“MI:0914”(association)	0.640
ZCCHC3	CGAS	psi-mi:“MI:0915”(physical association)	0.600
CGAS	ZCCHC3	psi-mi:“MI:0915”(physical association)	0.600
ZCCHC3	CGAS	psi-mi:“MI:0407”(direct interaction)	0.600
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
THAP3	CASC3	psi-mi:“MI:0914”(association)	0.530
PAIP2B	CASC3	psi-mi:“MI:0914”(association)	0.530
ILF2	RRP8	psi-mi:“MI:0914”(association)	0.530
HNRNPA1	PTCD1	psi-mi:“MI:0914”(association)	0.530
NIFK	RSL1D1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
H1-1	SURF6	psi-mi:“MI:0914”(association)	0.530
ELAVL2	CASC3	psi-mi:“MI:0914”(association)	0.530

BioGRID (246): ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Synthetic Lethality), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS), ZCCHC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUJ8, B8QB46, D3Z070, G3X912, O94762, P03121, P03122, P05433, P08345, P0DKA8, P0DOD0, P0DOD1, P0DOD4, P0DOD7, P0DOG8, P0DOH4, P0DOH5, P11365, P16424, P27552, P36780, P36795, P50768, P50769, P60323, P97287, Q13064, Q38740, Q38741, Q566Q8, Q5TKR9, Q60739, Q61033, Q61CX7, Q705F3, Q71M44, Q7YRZ9, Q80903, Q80910, Q80U38

Diamond homologs: Q8BPK2, Q9NUD5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 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
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	5	32.0×	5e-06
Transport of Mature Transcript to Cytoplasm	6	21.8×	4e-06
SARS-CoV-1 modulates host translation machinery	7	20.6×	8e-07
Eukaryotic Translation Initiation	6	17.6×	1e-05
Cap-dependent Translation Initiation	6	17.6×	1e-05
Formation of the ternary complex, and subsequently, the 43S complex	8	16.4×	7e-07
Eukaryotic Translation Elongation	6	15.9×	2e-05
Nonsense-Mediated Decay (NMD)	7	15.5×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	5	36.5×	3e-05
chromosome condensation	5	27.4×	9e-05
cytoplasmic translation	12	14.4×	3e-08
regulation of alternative mRNA splicing, via spliceosome	9	14.3×	5e-06
ribosomal small subunit biogenesis	9	13.3×	6e-06
mRNA transport	6	10.3×	1e-03
negative regulation of translation	8	10.2×	1e-04
RNA processing	6	8.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

19 predictions. Top by Δscore:

Variant	Effect	Δscore
20:298437:TGA:T	donor_gain	0.7000
20:298471:G:T	donor_gain	0.6300
20:299708:G:GC	acceptor_gain	0.5400
20:298471:G:GT	donor_gain	0.5300
20:299704:ACTT:A	acceptor_gain	0.4700
20:298455:T:A	donor_gain	0.4300
20:298889:A:C	acceptor_gain	0.4300
20:298081:C:A	acceptor_gain	0.4200
20:298438:GAA:G	donor_gain	0.4200
20:298439:AAA:A	donor_gain	0.4200
20:299704:A:AG	acceptor_gain	0.3500
20:298080:T:TA	acceptor_gain	0.3400
20:299705:C:G	acceptor_gain	0.3300
20:299705:CTTG:C	acceptor_gain	0.2600
20:298069:C:CT	acceptor_gain	0.2400
20:299689:A:AG	acceptor_gain	0.2200
20:298087:CCGCA:C	acceptor_gain	0.2100
20:299690:A:G	acceptor_gain	0.2100
20:298086:TCCGC:T	acceptor_gain	0.2000

AlphaMissense

2617 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:298220:T:C	F212L	1.000
20:298222:C:A	F212L	1.000
20:298222:C:G	F212L	1.000
20:298233:T:C	F216S	1.000
20:298260:T:C	F225S	1.000
20:298303:G:C	W239C	1.000
20:298303:G:T	W239C	1.000
20:298356:T:A	I257N	1.000
20:298362:T:C	F259S	1.000
20:298388:G:C	D268H	1.000
20:298400:T:A	W272R	1.000
20:298400:T:C	W272R	1.000
20:298404:T:A	L273H	1.000
20:298404:T:C	L273P	1.000
20:298448:G:C	D288H	1.000
20:298449:A:T	D288V	1.000
20:298463:T:A	W293R	1.000
20:298463:T:C	W293R	1.000
20:298465:G:C	W293C	1.000
20:298465:G:T	W293C	1.000
20:298470:G:A	G295E	1.000
20:298545:G:A	G320E	1.000
20:298556:G:C	G324R	1.000
20:298557:G:A	G324D	1.000
20:298589:T:C	C335R	1.000
20:298590:G:A	C335Y	1.000
20:298591:C:G	C335W	1.000
20:298592:T:C	F336L	1.000
20:298594:T:A	F336L	1.000
20:298594:T:G	F336L	1.000

dbSNP variants (sampled 300 via entrez): RS1000529446 (20:299101 C>T), RS1000967399 (20:297158 G>A,T), RS1001103162 (20:296897 A>G), RS1001536440 (20:297697 G>A,C,T), RS1003377487 (20:300646 C>T), RS1003621282 (20:295624 G>A), RS1004787800 (20:299279 T>C), RS1004975429 (20:299880 C>T), RS1005425290 (20:299511 T>C), RS1006573321 (20:297296 G>A), RS1007272780 (20:296395 C>T), RS1009286414 (20:299012 C>G,T), RS1009423738 (20:298869 A>C,G,T), RS1009769886 (20:297173 A>T), RS1010106888 (20:298693 C>T)

Disease associations

OMIM: gene MIM:618326 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007010_4	Logical memory (delayed recall)	6.000000e-07
GCST007011_4	Logical memory (immediate recall)	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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