ZC3H12C

Summary

ZC3H12C (zinc finger CCCH-type containing 12C, HGNC:29362) is a protein-coding gene on chromosome 11q22.3, encoding Probable ribonuclease ZC3H12C (Q9C0D7). May function as RNase and regulate the levels of target RNA species.

Predicted to enable RNA endonuclease activity and mRNA binding activity. Predicted to be active in cytoplasmic ribonucleoprotein granule and nucleus.

Source: NCBI Gene 85463 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 116 total
• MANE Select transcript: NM_033390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29362
Approved symbol	ZC3H12C
Name	zinc finger CCCH-type containing 12C
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1726, MCPIP3
Ensembl gene	ENSG00000149289
Ensembl biotype	protein_coding
OMIM	615001
Entrez	85463

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000278590, ENST00000453089, ENST00000528673

RefSeq mRNA: 2 — MANE Select: NM_033390 NM_001411037, NM_033390

CCDS: CCDS44727, CCDS91583

Canonical transcript exons

ENST00000278590 — 6 exons

Exon	Start	End
ENSE00000989791	110163273	110163379
ENSE00001185235	110164341	110171841
ENSE00001415154	110136663	110137414
ENSE00001551834	110093392	110093432
ENSE00001619254	110152919	110153058
ENSE00001751316	110159256	110159490

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 92.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4230 / max 1154.2768, expressed in 1612 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116575	4.5353	1338
116576	3.1144	927
116586	1.1352	149
116577	1.0821	565
116582	1.0404	591
116579	0.9963	275
116578	0.5844	209
116573	0.2983	91
116581	0.1906	63
116583	0.1826	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	92.24	gold quality
epithelial cell of pancreas	CL:0000083	92.12	silver quality
biceps brachii	UBERON:0001507	90.01	gold quality
deltoid	UBERON:0001476	89.60	gold quality
upper leg skin	UBERON:0004262	89.04	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.04	gold quality
adrenal tissue	UBERON:0018303	89.03	gold quality
oviduct epithelium	UBERON:0004804	88.85	gold quality
cartilage tissue	UBERON:0002418	88.72	gold quality
pancreatic ductal cell	CL:0002079	88.28	gold quality
heart right ventricle	UBERON:0002080	87.75	gold quality
palpebral conjunctiva	UBERON:0001812	87.61	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.72	gold quality
visceral pleura	UBERON:0002401	86.48	gold quality
parietal pleura	UBERON:0002400	86.04	gold quality
quadriceps femoris	UBERON:0001377	85.26	gold quality
colonic mucosa	UBERON:0000317	84.73	gold quality
vastus lateralis	UBERON:0001379	84.47	gold quality
eye	UBERON:0000970	84.05	gold quality
skin of hip	UBERON:0001554	83.45	gold quality
skeletal muscle tissue	UBERON:0001134	83.43	gold quality
gastrocnemius	UBERON:0001388	82.60	gold quality
skeletal muscle organ	UBERON:0014892	82.53	gold quality
germinal epithelium of ovary	UBERON:0001304	82.39	gold quality
buccal mucosa cell	CL:0002336	82.26	silver quality
muscle tissue	UBERON:0002385	82.03	gold quality
myocardium	UBERON:0002349	82.01	gold quality
ventricular zone	UBERON:0003053	81.91	gold quality
muscle of leg	UBERON:0001383	81.87	gold quality
calcaneal tendon	UBERON:0003701	81.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

402 targeting ZC3H12C, 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-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-568	99.98	69.86	2084

Literature-anchored findings (GeneRIF, showing 4)

• MCPIP1, 2, 3, and 4, encoded by four genes, Zc3h12a, Zc3h12b, Zc3h12c, and Zc3h12d, respectively, regulates macrophage activation. (PMID:18178554)
• Thus Zc3h12c is an endogenous inhibitor of TNFalpha-induced inflammatory signalling in HUVECs and might be a therapeutic target in vascular inflammatory diseases. (PMID:23360436)
• The Gene-based analyses revealed four significant associations in the WT1, ZC3H12C, DLGAP2, and GPR1 genes at p < 0.05. in this study. (PMID:25391383)
• The RNase MCPIP3 promotes skin inflammation by orchestrating myeloid cytokine response. (PMID:34215755)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zc3h12c	ENSMUSG00000035164
rattus_norvegicus	Zc3h12c	ENSRNOG00000012470
drosophila_melanogaster	Regnase-1	FBGN0038769
drosophila_melanogaster	CG42360	FBGN0259742
caenorhabditis_elegans		WBGENE00013107
caenorhabditis_elegans	rege-1	WBGENE00016260
caenorhabditis_elegans		WBGENE00021287
caenorhabditis_elegans		WBGENE00021998
caenorhabditis_elegans		WBGENE00022003

Paralogs (6): KHNYN (ENSG00000100441), ZC3H12B (ENSG00000102053), N4BP1 (ENSG00000102921), ZC3H12A (ENSG00000163874), ZC3H12D (ENSG00000178199), NYNRIN (ENSG00000205978)

Protein

Protein identifiers

Probable ribonuclease ZC3H12C — Q9C0D7 (reviewed: Q9C0D7)

Alternative names: MCP-induced protein 3, Zinc finger CCCH domain-containing protein 12C

All UniProt accessions (2): Q9C0D7, E9PP00

UniProt curated annotations — full annotation on UniProt →

Function. May function as RNase and regulate the levels of target RNA species.

Induction. By cytokines (TNF and interleukin-1) in acute monocytic leukemia cell line THP-1 cells.

Similarity. Belongs to the ZC3H12 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C0D7-1	1	yes
Q9C0D7-2	2

RefSeq proteins (2): NP_001397966, NP_203748* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR021869	RNase_Zc3h12_NYN	Domain
IPR040546	Rege-1_UBA-like	Domain
IPR040757	Regnase_1/ZC3H12_C	Domain
IPR051101	ZC3H12/N4BP1_RNase_Reg	Family

Pfam: PF11977, PF18039, PF18561

UniProt features (16 total): region of interest 5, compositionally biased region 4, sequence conflict 2, chain 1, domain 1, modified residue 1, splice variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0D7-F1	58.15	0.22

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): 230

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 339 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOMF_NUCLEASE_ACTIVITY, chr11q22, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, FOSTER_TOLERANT_MACROPHAGE_DN, GOMF_RNA_ENDONUCLEASE_ACTIVITY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, ZHAN_MULTIPLE_MYELOMA_LB_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (9): mRNA binding (GO:0003729), RNA endonuclease activity (GO:0004521), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), molecular_function (GO:0003674), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasmic ribonucleoprotein granule (GO:0036464), cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	1
endonuclease activity	1
RNA nuclease activity	1
transition metal ion binding	1
catalytic activity	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
ribonucleoprotein granule	1

Protein interactions and networks

STRING

552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZC3H12C	KBTBD3	Q8NAB2	533
ZC3H12C	ZFAT	Q9P243	508
ZC3H12C	GLIS3	Q8NEA6	492
ZC3H12C	AGBL3	Q8NEM8	482
ZC3H12C	CARD14	Q9BXL6	479
ZC3H12C	RC3H2	Q9HBD1	479
ZC3H12C	MCCC1	Q96RQ3	456
ZC3H12C	SVOPL	Q8N434	454
ZC3H12C	RC3H1	Q5TC82	437
ZC3H12C	HECW1	Q76N89	427
ZC3H12C	TAGAP	Q8N103	426
ZC3H12C	ZFP90	Q8TF47	426
ZC3H12C	MAGI2	Q86UL8	423
ZC3H12C	SLC38A4	Q969I6	421
ZC3H12C	HTR5A	P47898	412

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TRAF4	ZC3H12C	psi-mi:“MI:0915”(physical association)	0.560
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
SCGN	CNOT1	psi-mi:“MI:0914”(association)	0.350
IRAK2	SNRNP200	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TRAF4	ZC3H12C	psi-mi:“MI:0915”(physical association)	0.000
	ZC3H12C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): ZC3H12C (Affinity Capture-MS), ZC3H12C (Affinity Capture-RNA), ZC3H12C (Two-hybrid), ZC3H12C (Affinity Capture-MS), ZC3H12C (Affinity Capture-MS), CCT6A (Cross-Linking-MS (XL-MS)), ZC3H12C (Proximity Label-MS), ZC3H12C (Affinity Capture-RNA), ZC3H12C (Affinity Capture-MS)

ESM2 similar proteins: A0JPN4, A2A288, A2ARK0, A6ND36, A6QQJ8, A7E316, E9Q0S6, E9Q2Z1, O15037, O54714, O54967, O70260, O70405, O75385, O94983, P42335, P48778, Q07912, Q0P4K8, Q17R13, Q1LVK9, Q32PJ7, Q4V8I3, Q5D1E7, Q5D1E8, Q5DTV4, Q5HYM0, Q5JV73, Q5SWY7, Q5SXM2, Q5U2X5, Q5XIS1, Q68CZ2, Q6A037, Q6IRU7, Q6P1H6, Q6S5L8, Q7TP65, Q7TSG2, Q80U38

Diamond homologs: A0JPN4, A2A288, A6QQJ8, O15037, O75113, Q1LVK9, Q5D1E7, Q5D1E8, Q5DTV4, Q5DTZ0, Q5HYM0, Q5ZLE9, Q6A037, Q6DJS0, Q7ZXG4, Q80U38, Q8BIY3, Q95YE2, Q9C0D7, Q9P2P1, A6NKG5, Q8I7P9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

900 predictions. Top by Δscore:

Variant	Effect	Δscore
11:110131107:G:GG	donor_gain	1.0000
11:110159491:G:GG	donor_gain	1.0000
11:110131102:CTAAC:C	donor_gain	0.9900
11:110131103:TAAC:T	donor_gain	0.9900
11:110131103:TAACG:T	donor_loss	0.9900
11:110131104:AACGT:A	donor_loss	0.9900
11:110131105:AC:A	donor_gain	0.9900
11:110131106:CG:C	donor_loss	0.9900
11:110131107:GTGA:G	donor_loss	0.9900
11:110131108:T:A	donor_loss	0.9900
11:110134863:T:G	donor_gain	0.9900
11:110137411:TGAGG:T	donor_loss	0.9900
11:110137413:AGGT:A	donor_loss	0.9900
11:110137414:GGTA:G	donor_loss	0.9900
11:110137415:GT:G	donor_loss	0.9900
11:110152896:A:G	acceptor_gain	0.9900
11:110159253:CA:C	acceptor_loss	0.9900
11:110159254:A:AC	acceptor_loss	0.9900
11:110159254:A:AG	acceptor_gain	0.9900
11:110159255:G:GG	acceptor_gain	0.9900
11:110159255:GATC:G	acceptor_gain	0.9900
11:110159255:GATCA:G	acceptor_gain	0.9900
11:110159440:G:GT	donor_gain	0.9900
11:110159443:G:GT	donor_gain	0.9900
11:110159486:GACAA:G	donor_gain	0.9900
11:110159487:ACAAG:A	donor_loss	0.9900
11:110159489:AA:A	donor_gain	0.9900
11:110159490:AGTA:A	donor_loss	0.9900
11:110159491:G:C	donor_loss	0.9900
11:110159492:TAA:T	donor_loss	0.9900

AlphaMissense

5840 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:110137143:T:C	F168L	1.000
11:110137144:T:C	F168S	1.000
11:110137144:T:G	F168C	1.000
11:110137145:T:A	F168L	1.000
11:110137145:T:G	F168L	1.000
11:110137147:C:A	A169E	1.000
11:110137156:T:C	L172S	1.000
11:110137189:T:C	L183P	1.000
11:110137228:T:C	L196S	1.000
11:110137228:T:G	L196W	1.000
11:110137237:T:A	L199H	1.000
11:110137237:T:C	L199P	1.000
11:110137240:T:A	V200D	1.000
11:110137387:T:A	V249D	1.000
11:110137392:G:A	D251N	1.000
11:110137392:G:C	D251H	1.000
11:110137393:A:C	D251A	1.000
11:110137393:A:G	D251G	1.000
11:110137393:A:T	D251V	1.000
11:110137394:T:A	D251E	1.000
11:110137394:T:G	D251E	1.000
11:110137395:G:C	G252R	1.000
11:110137395:G:T	G252C	1.000
11:110137396:G:A	G252D	1.000
11:110137396:G:T	G252V	1.000
11:110137398:A:C	S253R	1.000
11:110137399:G:T	S253I	1.000
11:110137400:C:A	S253R	1.000
11:110137400:C:G	S253R	1.000
11:110137401:A:C	N254H	1.000

dbSNP variants (sampled 300 via entrez): RS1000066502 (11:110123519 C>T), RS1000132122 (11:110158461 G>A,C), RS1000156850 (11:110106852 A>T), RS1000180235 (11:110156273 G>T), RS1000185429 (11:110161976 C>A), RS1000236322 (11:110162215 A>G), RS1000367643 (11:110130642 G>T), RS1000411064 (11:110148208 T>C), RS1000420646 (11:110143748 C>G), RS1000482570 (11:110163688 C>A), RS1000504793 (11:110113952 T>C), RS1000515917 (11:110158013 T>C), RS1000549093 (11:110112349 C>T), RS1000572185 (11:110112554 T>G), RS1000587750 (11:110158325 C>A)

Disease associations

OMIM: gene MIM:615001 | disease phenotypes: MIM:301050

GenCC curated gene-disease

Mondo (1): X-linked Alport syndrome (MONDO:0010520)

Orphanet (2): Alport syndrome (Orphanet:63), X-linked Alport syndrome (Orphanet:88917)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003268_9	Psoriasis vulgaris	9.000000e-09
GCST005527_30	Psoriasis	8.000000e-13
GCST005537_79	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	8.000000e-12
GCST005537_80	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-09
GCST006431_14	Plasma parathyroid hormone levels	9.000000e-07
GCST006611_74	HDL cholesterol	4.000000e-09
GCST006666_1	Lipid traits (pleiotropy) (HIPO component 1)	3.000000e-08
GCST008158_85	Body mass index	4.000000e-06
GCST009151_10	High density lipoprotein cholesterol levels	2.000000e-13
GCST010241_25	Apolipoprotein A1 levels	2.000000e-17
GCST010242_314	HDL cholesterol levels	4.000000e-14

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004340	body mass index
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	7
trichostatin A	affects cotreatment, decreases expression	3
entinostat	affects cotreatment, decreases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Cyclosporine	increases expression	2
Asbestos, Crocidolite	increases expression, affects expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
MT19c compound	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Leflunomide	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2PI	HAP1 ZC3H12C (-) 1	Cancer cell line	Male
CVCL_E2PJ	HAP1 ZC3H12C (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04937907	PHASE2	COMPLETED	Study of Hydroxychloroquine in Patients With X-linked Alport Syndrome in China (CHXLAS)
NCT07523581	PHASE2	NOT_YET_RECRUITING	EXACT Study: A Blinded Study in Patients With Alport Syndrome to Evaluate Exaluren Efficacy and Safety
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns