ZC3H15

Summary

ZC3H15 (zinc finger CCCH-type containing 15, HGNC:29528) is a protein-coding gene on chromosome 2q32.1, encoding Zinc finger CCCH domain-containing protein 15 (Q8WU90). Protects DRG1 from proteolytic degradation.

Enables RNA binding activity and cadherin binding activity. Involved in positive regulation of GTPase activity. Located in cytosol.

Source: NCBI Gene 55854 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_018471

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29528
Approved symbol	ZC3H15
Name	zinc finger CCCH-type containing 15
Location	2q32.1
Locus type	gene with protein product
Status	Approved
Aliases	DFRP1, LEREPO4
Ensembl gene	ENSG00000065548
Ensembl biotype	protein_coding
OMIM	619704
Entrez	55854

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000337859, ENST00000421536, ENST00000437396, ENST00000445547, ENST00000468120, ENST00000477672, ENST00000481101, ENST00000496289, ENST00000498757, ENST00000718440, ENST00000874883, ENST00000874884, ENST00000874885, ENST00000921306, ENST00000921307, ENST00000921308, ENST00000921309, ENST00000921310, ENST00000946960, ENST00000946961

RefSeq mRNA: 1 — MANE Select: NM_018471 NM_018471

CCDS: CCDS42791

Canonical transcript exons

ENST00000337859 — 10 exons

Exon	Start	End
ENSE00000883169	186502496	186502587
ENSE00001245622	186508543	186509361
ENSE00001418215	186486260	186486457
ENSE00003466243	186500182	186500293
ENSE00003497673	186501273	186501425
ENSE00003579933	186506713	186506836
ENSE00003641962	186504032	186504214
ENSE00003666046	186495233	186495334
ENSE00003676760	186505740	186505841
ENSE00003684892	186505451	186505597

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 89.9346 / max 1808.5554, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24096	86.4809	1827
24095	1.6221	984
24094	1.6214	1008
24103	0.1561	34
24102	0.0541	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.57	gold quality
male germ cell	CL:0000015	98.27	gold quality
calcaneal tendon	UBERON:0003701	97.98	gold quality
secondary oocyte	CL:0000655	97.74	gold quality
pons	UBERON:0000988	97.71	gold quality
pylorus	UBERON:0001166	97.63	gold quality
pericardium	UBERON:0002407	97.62	gold quality
dorsal root ganglion	UBERON:0000044	97.46	gold quality
oocyte	CL:0000023	97.41	gold quality
choroid plexus epithelium	UBERON:0003911	97.32	gold quality
vena cava	UBERON:0004087	97.23	gold quality
parietal lobe	UBERON:0001872	97.21	gold quality
postcentral gyrus	UBERON:0002581	97.18	gold quality
renal medulla	UBERON:0000362	97.11	gold quality
substantia nigra pars compacta	UBERON:0001965	97.10	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.02	gold quality
cartilage tissue	UBERON:0002418	97.01	gold quality
cortical plate	UBERON:0005343	96.98	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.97	gold quality
cardia of stomach	UBERON:0001162	96.92	gold quality
superior frontal gyrus	UBERON:0002661	96.92	gold quality
superior vestibular nucleus	UBERON:0007227	96.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.90	gold quality
jejunal mucosa	UBERON:0000399	96.83	gold quality
trigeminal ganglion	UBERON:0001675	96.81	gold quality
hair follicle	UBERON:0002073	96.80	gold quality
adrenal tissue	UBERON:0018303	96.79	gold quality
cauda epididymis	UBERON:0004360	96.77	gold quality
ventral tegmental area	UBERON:0002691	96.74	gold quality
tongue squamous epithelium	UBERON:0006919	96.73	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	2098.22
E-MTAB-4850	no	742.55
E-HCAD-31	no	1.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRD1

miRNA regulators (miRDB)

45 targeting ZC3H15, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-532-5P	98.43	67.53	760

Literature-anchored findings (GeneRIF, showing 6)

• down-regulation of LEREPO4 expression caused a significant inhibition of HIV replication (PMID:20925576)
• it is hypothesized that ZC3H15 may interact with TRAF-2 functionally within the NF-kappaB pathway, and may be explored as a potential target in acute myeloid leukemia (PMID:23624947)
• Lerepo4 action leaves Drg1 affinity for nucleotides unaffected, feasibly favoring a switch I reorientation, mainly via the TGS domain. (PMID:23711155)
• ZC3H15 is an independent prognostic marker in hepatocellular carcinoma patients that is clinicopathologically associated with tumor invasion and serum a-fetoprotein levels. (PMID:27191988)
• ZC3H15 Correlates with a Poor Prognosis and Tumor Progression in Melanoma. (PMID:34988227)
• ZC3H15 promotes glioblastoma progression through regulating EGFR stability. (PMID:35027542)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	zc3h15	ENSDARG00000015889
mus_musculus	Zc3h15	ENSMUSG00000027091
rattus_norvegicus	Zc3h15	ENSRNOG00000005256
rattus_norvegicus	AC115670.2	ENSRNOG00000060002
drosophila_melanogaster	CG8635	FBGN0033317
caenorhabditis_elegans	F27D4.4	WBGENE00009189

Protein

Protein identifiers

Zinc finger CCCH domain-containing protein 15 — Q8WU90 (reviewed: Q8WU90)

Alternative names: DRG family-regulatory protein 1, Likely ortholog of mouse immediate early response erythropoietin 4

All UniProt accessions (4): Q8WU90, F8WB26, F8WF67, H7C466

UniProt curated annotations — full annotation on UniProt →

Function. Protects DRG1 from proteolytic degradation. Stimulates DRG1 GTPase activity likely by increasing the affinity for the potassium ions.

Subunit / interactions. Interacts with DRG1; this interaction prevents DRG1 poly-ubiquitination and degradation by proteasome. DRG1-ZC3H15/DFRP1 complex co-sediments with polysomes. Associates with microtubules.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the ZC3H15/TMA46 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WU90-1	1	yes
Q8WU90-2	2

RefSeq proteins (1): NP_060941* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR032378	ZC3H15/TMA46_C	Domain
IPR036855	Znf_CCCH_sf	Homologous_superfamily

Pfam: PF00642, PF16543

UniProt features (33 total): sequence conflict 10, region of interest 5, compositionally biased region 4, modified residue 4, splice variant 3, zinc finger region 2, sequence variant 2, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WU90-F1	71.77	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 (4): 231, 351, 360, 381

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9629569	Protein hydroxylation

MSigDB gene sets: 142 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_PEPTIDE, MORF_UBE2I, GOBP_REGULATION_OF_GTPASE_ACTIVITY, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, MORF_RAF1, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GNF2_ELAC2, MORF_AATF, MORF_SART1

GO Biological Process (3): cytoplasmic translation (GO:0002181), cytokine-mediated signaling pathway (GO:0019221), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (5): RNA binding (GO:0003723), zinc ion binding (GO:0008270), cadherin binding (GO:0045296), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
translation	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
nucleic acid binding	1
transition metal ion binding	1
cell adhesion molecule binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZC3H15	RWDD1	Q9H446	854
ZC3H15	DRG2	P55039	805
ZC3H15	DRG1	Q9Y295	735
ZC3H15	RSPRY1	Q96DX4	557
ZC3H15	CCDC106	Q9BWC9	539
ZC3H15	FIZ1	Q96SL8	503
ZC3H15	NUDT13	Q86X67	497
ZC3H15	METTL22	Q9BUU2	480
ZC3H15	TPRA1	Q86W33	458
ZC3H15	MRPS34	P82930	448
ZC3H15	HTATSF1	O43719	447
ZC3H15	FBXO9	Q9UK97	446
ZC3H15	DUSP28	Q4G0W2	441
ZC3H15	PCMT1	P22061	435
ZC3H15	GTF3C1	Q12789	433

IntAct

86 interactions, top by confidence:

A	B	Type	Score
DRG1	ZC3H15	psi-mi:“MI:0915”(physical association)	0.930
ZC3H15	DRG1	psi-mi:“MI:0915”(physical association)	0.930
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CCT6A	TXNDC9	psi-mi:“MI:0914”(association)	0.530
DRG1	LRRC41	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
CSNK2A1	ZC3H15	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CC2D2A	OFD1	psi-mi:“MI:2364”(proximity)	0.420
ZC3H15		psi-mi:“MI:0915”(physical association)	0.370
ZC3H15	C8orf33	psi-mi:“MI:0915”(physical association)	0.370
ZC3H15	TNNT1	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
TM9SF4		psi-mi:“MI:0914”(association)	0.350
Fbxo21	ESYT2	psi-mi:“MI:0914”(association)	0.350
MRPL50	MRPL43	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
BRD1	MRPS14	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
DRG1	LRRC41	psi-mi:“MI:0914”(association)	0.350
N	IGF2BP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (159): ZC3H15 (Two-hybrid), ZC3H15 (Affinity Capture-MS), ZC3H15 (Affinity Capture-MS), ABCF2 (Co-fractionation), DRG1 (Co-fractionation), FAF1 (Co-fractionation), GINS3 (Co-fractionation), HMGN5 (Co-fractionation), ZC3H15 (Co-fractionation), ZC3H15 (Affinity Capture-MS), ZC3H15 (Synthetic Lethality), ZC3H15 (Affinity Capture-MS), ZC3H15 (Proximity Label-MS), ZC3H15 (Proximity Label-MS), ZC3H15 (Proximity Label-MS)

ESM2 similar proteins: A0JNI5, A2AQ19, D3ZTQ1, O43290, O43395, P21675, P35269, P49140, Q02614, Q12872, Q13435, Q2KIA6, Q2KIT1, Q3THK3, Q3TIV5, Q3U155, Q3UJB0, Q3USH5, Q53F19, Q5EA53, Q5HZB6, Q5R5F1, Q5R5J3, Q5RAD5, Q5U3K5, Q5XIW8, Q5ZIH9, Q5ZJ85, Q5ZM19, Q60544, Q6AY96, Q6PII3, Q6U6G5, Q75QI0, Q80UV9, Q8BVA4, Q8BZR9, Q8CFC7, Q8N2M8, Q8WU90

Diamond homologs: A4IGY3, A8WMM4, Q0JHZ2, Q12000, Q1RMM1, Q28Y69, Q3TIV5, Q54DA5, Q5H7N8, Q6DD06, Q6U6G5, Q7JWR9, Q803J8, Q8WU90, Q93618, Q9SK74, Q9USV4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Translation	8	7.0×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	6	12.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1607 predictions. Top by Δscore:

Variant	Effect	Δscore
2:186486455:GAA:G	donor_gain	1.0000
2:186486456:AA:A	donor_gain	1.0000
2:186486458:G:GG	donor_gain	1.0000
2:186486458:G:T	donor_loss	1.0000
2:186486459:TGA:T	donor_loss	1.0000
2:186486460:GAG:G	donor_loss	1.0000
2:186495227:AT:A	acceptor_gain	1.0000
2:186495228:T:G	acceptor_gain	1.0000
2:186495228:T:TA	acceptor_gain	1.0000
2:186495230:TAGG:T	acceptor_loss	1.0000
2:186495231:A:AG	acceptor_gain	1.0000
2:186495231:A:C	acceptor_loss	1.0000
2:186495231:AG:A	acceptor_gain	1.0000
2:186495232:G:GC	acceptor_gain	1.0000
2:186495232:GG:G	acceptor_gain	1.0000
2:186495232:GGA:G	acceptor_gain	1.0000
2:186495232:GGAC:G	acceptor_gain	1.0000
2:186495232:GGACA:G	acceptor_gain	1.0000
2:186495330:GTCAG:G	donor_gain	1.0000
2:186495331:TCAG:T	donor_gain	1.0000
2:186495332:CAG:C	donor_gain	1.0000
2:186495332:CAGG:C	donor_loss	1.0000
2:186495333:AG:A	donor_gain	1.0000
2:186495334:GG:G	donor_gain	1.0000
2:186495335:G:GG	donor_gain	1.0000
2:186500284:A:AG	donor_gain	1.0000
2:186500284:A:G	donor_gain	1.0000
2:186501421:AAAAG:A	donor_loss	1.0000
2:186501423:AAGGT:A	donor_loss	1.0000
2:186501425:GGT:G	donor_loss	1.0000

AlphaMissense

2865 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:186495233:G:C	D26H	1.000
2:186495234:A:C	D26A	1.000
2:186495234:A:T	D26V	1.000
2:186495236:A:G	K27E	1.000
2:186495238:A:C	K27N	1.000
2:186495238:A:T	K27N	1.000
2:186495242:T:A	F29I	1.000
2:186495242:T:C	F29L	1.000
2:186495242:T:G	F29V	1.000
2:186495243:T:C	F29S	1.000
2:186495243:T:G	F29C	1.000
2:186495244:C:A	F29L	1.000
2:186495244:C:G	F29L	1.000
2:186495245:G:A	G30S	1.000
2:186495245:G:C	G30R	1.000
2:186495245:G:T	G30C	1.000
2:186495246:G:A	G30D	1.000
2:186495246:G:T	G30V	1.000
2:186495249:T:C	L31S	1.000
2:186495251:A:G	K32E	1.000
2:186495252:A:T	K32M	1.000
2:186495253:G:C	K32N	1.000
2:186495253:G:T	K32N	1.000
2:186495254:A:G	N33D	1.000
2:186495256:T:A	N33K	1.000
2:186495256:T:G	N33K	1.000
2:186495257:A:G	K34E	1.000
2:186495259:G:C	K34N	1.000
2:186495259:G:T	K34N	1.000
2:186495263:G:A	G36R	1.000

dbSNP variants (sampled 300 via entrez): RS1000154487 (2:186491584 A>G), RS1000161406 (2:186504007 C>A), RS1000166880 (2:186504320 A>AG), RS1000236239 (2:186499101 C>T), RS1000476197 (2:186493138 A>G), RS1000516414 (2:186497956 C>T), RS1000628294 (2:186504426 G>A), RS1001165677 (2:186493189 T>C,G), RS1001171077 (2:186509730 T>A), RS1001520923 (2:186490328 T>A), RS1001751831 (2:186491448 T>C), RS1001788345 (2:186502698 A>T), RS1001840710 (2:186502876 G>T), RS1001900355 (2:186484471 T>C), RS1001974151 (2:186484263 T>C)

Disease associations

OMIM: gene MIM:619704 | 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
GCST010320_60	PR interval	1.000000e-07
GCST010321_196	PR interval	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	increases expression, decreases expression, increases activity	3
Air Pollutants	increases expression, decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
sodium arsenate	decreases expression	1
kojic acid	decreases expression	1
methylparaben	increases expression	1
perfluorooctanoic acid	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	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
bisphenol B	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
bisphenol AF	increases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gold	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phthalic Acids	increases methylation	1
Ribonucleotides	affects binding	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3LK	Abcam HEK293T ZC3H15 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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