ZCCHC14

Summary

ZCCHC14 (zinc finger CCHC-type containing 14, HGNC:24134) is a protein-coding gene on chromosome 16q24.2, encoding Zinc finger CCHC domain-containing protein 14 (Q8WYQ9).

Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity.

Source: NCBI Gene 23174 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 186 total — 1 pathogenic
• MANE Select transcript: NM_015144

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24134
Approved symbol	ZCCHC14
Name	zinc finger CCHC-type containing 14
Location	16q24.2
Locus type	gene with protein product
Status	Approved
Aliases	BDG29, MGC14139
Ensembl gene	ENSG00000140948
Ensembl biotype	protein_coding
OMIM	620697
Entrez	23174

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000268616, ENST00000561928, ENST00000565193, ENST00000568020, ENST00000671377

RefSeq mRNA: 1 — MANE Select: NM_015144 NM_015144

CCDS: CCDS10961

Canonical transcript exons

ENST00000671377 — 13 exons

Exon	Start	End
ENSE00000945764	87414414	87414541
ENSE00000945765	87411516	87412976
ENSE00001113630	87415276	87415367
ENSE00001121393	87413055	87413195
ENSE00001121416	87417460	87417742
ENSE00001121421	87418847	87418901
ENSE00001121430	87419783	87419877
ENSE00001121440	87420607	87420716
ENSE00001121451	87423810	87423881
ENSE00001121463	87433128	87433201
ENSE00001121471	87460008	87460131
ENSE00003855726	87491669	87493024
ENSE00003897464	87406248	87410335

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 94.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3607 / max 143.7486, expressed in 1749 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158473	4.4408	1560
158474	4.4332	1490
158472	1.4867	757

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.57	gold quality
adult organism	UBERON:0007023	94.02	gold quality
endometrium epithelium	UBERON:0004811	93.78	gold quality
cortical plate	UBERON:0005343	93.04	gold quality
paraflocculus	UBERON:0005351	92.87	gold quality
oocyte	CL:0000023	92.48	gold quality
cerebellar vermis	UBERON:0004720	92.42	gold quality
skin of hip	UBERON:0001554	91.37	gold quality
testis	UBERON:0000473	91.17	gold quality
left testis	UBERON:0004533	90.87	gold quality
jejunal mucosa	UBERON:0000399	90.79	gold quality
right testis	UBERON:0004534	90.55	gold quality
sperm	CL:0000019	90.39	gold quality
male germ cell	CL:0000015	90.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.80	gold quality
urethra	UBERON:0000057	89.76	gold quality
ganglionic eminence	UBERON:0004023	89.58	gold quality
upper leg skin	UBERON:0004262	89.34	gold quality
parotid gland	UBERON:0001831	89.20	gold quality
jejunum	UBERON:0002115	88.81	gold quality
renal medulla	UBERON:0000362	88.78	gold quality
middle frontal gyrus	UBERON:0002702	88.51	gold quality
caput epididymis	UBERON:0004358	88.38	gold quality
ventricular zone	UBERON:0003053	88.25	gold quality
tibial artery	UBERON:0007610	88.23	gold quality
popliteal artery	UBERON:0002250	88.22	gold quality
seminal vesicle	UBERON:0000998	88.14	gold quality
synovial joint	UBERON:0002217	88.07	gold quality
cerebellum	UBERON:0002037	88.02	gold quality
palpebral conjunctiva	UBERON:0001812	87.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

257 targeting ZCCHC14, 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-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
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-4673	100.00	66.64	1490
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493

Literature-anchored findings (GeneRIF, showing 8)

• ZCCHC14 expression is associated with small vessel disease. (PMID:27997041)
• Plasma concentration of ZCCHC14 contributes to prognostic efficacy in intracerebral hemorrhage patients. (PMID:31646585)
• A Genome-wide CRISPR Screen Identifies ZCCHC14 as a Host Factor Required for Hepatitis B Surface Antigen Production. (PMID:31801065)
• Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing. (PMID:32451488)
• ZCCHC14 regulates proliferation and invasion of non-small cell lung cancer through the MAPK-P38 signalling pathway. (PMID:33345444)
• The ZCCHC14/TENT4 complex is required for hepatitis A virus RNA synthesis. (PMID:35867748)
• circRNA-ZCCHC14 affects the chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells by regulating GREM1 through miR-181a. (PMID:36804426)
• Biochemical analysis of the host factor activity of ZCCHC14 in hepatitis A virus replication. (PMID:38501662)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zcchc14	ENSDARG00000101242
mus_musculus	Zcchc14	ENSMUSG00000061410
rattus_norvegicus	Zcchc14	ENSRNOG00000018226
drosophila_melanogaster	CG10492	FBGN0032748
caenorhabditis_elegans	gls-1	WBGENE00007975

Paralogs (1): ZCCHC2 (ENSG00000141664)

Protein

Protein identifiers

Zinc finger CCHC domain-containing protein 14 — Q8WYQ9 (reviewed: Q8WYQ9)

Alternative names: BDG-29

All UniProt accessions (4): Q8WYQ9, A0A590UJW6, A0A5F9XIK1, H3BS18

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WYQ9-1	1	yes
Q8WYQ9-2	2

RefSeq proteins (1): NP_055959* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR001878	Znf_CCHC	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR037632	ZCCH14_SAM	Domain
IPR042344	ZCCHC14	Family

Pfam: PF00098, PF00536

UniProt features (19 total): compositionally biased region 6, region of interest 6, sequence variant 4, chain 1, zinc finger region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYQ9-F1	50.94	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 214 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, TATTATA_MIR374, CACCAGC_MIR138, CTATGCA_MIR153, PAX2_01, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, CAATGCA_MIR33, ABE_VEGFA_TARGETS_2HR, ATTCTTT_MIR186, AAAGGGA_MIR204_MIR211, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P

GO Biological Process (0):

GO Molecular Function (5): nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), phosphatidylinositol binding (GO:0035091), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
transition metal ion binding	1
anion binding	1
cation binding	1

Protein interactions and networks

STRING

2346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZCCHC14	TENT4B	Q8NDF8	648
ZCCHC14	TENT4A	Q5XG87	643
ZCCHC14	ICA1L	Q8NDH6	506
ZCCHC14	ZZEF1	O43149	481
ZCCHC14	C16orf95	Q9H693	448
ZCCHC14	A0A087WT04	A0A087WT04	447
ZCCHC14	KLHDC4	Q8TBB5	447
ZCCHC14	KLHL18	O94889	426
ZCCHC14	NAE1	Q13564	422
ZCCHC14	DCUN1D3	Q8IWE4	422
ZCCHC14	AGAP1	Q9UPQ3	422
ZCCHC14	ANKRD11	Q6UB99	418
ZCCHC14	SLC25A44	Q96H78	417
ZCCHC14	SKIL	P12756	407
ZCCHC14	GPR152	Q8TDT2	407

IntAct

31 interactions, top by confidence:

A	B	Type	Score
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CYSRT1	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.560
PRR20D	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.560
MYOG	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.560
TNS2	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.560
MYO15B	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.560
FHL3	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG4	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.560
USP54	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.560
ZCCHC14	ENPEP	psi-mi:“MI:0915”(physical association)	0.400
SMAD3	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.370
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
RMND5A	HTRA2	psi-mi:“MI:0914”(association)	0.350
SQSTM1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
ZCCHC14	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
ZCCHC14	PRR20D	psi-mi:“MI:0915”(physical association)	0.000
ZCCHC14	MYOG	psi-mi:“MI:0915”(physical association)	0.000
ZCCHC14	USP54	psi-mi:“MI:0915”(physical association)	0.000
TNS2	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.000
MYO15B	ZCCHC14	psi-mi:“MI:0915”(physical association)	0.000
ZCCHC14	FHL3	psi-mi:“MI:0915”(physical association)	0.000
ZCCHC14	PLEKHG4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (60): ZCCHC14 (Affinity Capture-MS), ZCCHC14 (Two-hybrid), ZCCHC14 (Affinity Capture-MS), ZCCHC14 (Affinity Capture-MS), ZCCHC14 (Affinity Capture-MS), ZCCHC14 (Affinity Capture-RNA), ZCCHC14 (Affinity Capture-RNA), ZCCHC14 (Synthetic Lethality), ZCCHC14 (Two-hybrid), ZCCHC14 (Two-hybrid), USP54 (Two-hybrid), FHL3 (Two-hybrid), PLEKHG4 (Two-hybrid), CYSRT1 (Two-hybrid), PRR20B (Two-hybrid)

ESM2 similar proteins: A0A0R4IYX6, A5D7F8, A5D8S5, A5X7A0, B2RQC2, B5DEH0, D3YUB6, D3ZEN0, D3ZU96, D4A0X3, E1B9W9, E9Q9W7, F6NSX9, G5E5X0, O70405, O75385, P00519, P42684, Q08EC4, Q28E95, Q3TN34, Q498M5, Q4JIM5, Q5RBI7, Q5RBR0, Q5SPL2, Q5SSZ5, Q5ZM88, Q68CZ2, Q69ZI1, Q6NRD3, Q71F54, Q76L83, Q7TNC6, Q7Z6J0, Q80VX4, Q8BX22, Q8BZT2, Q8C120, Q8IYT8

Diamond homologs: J9VVN9, Q08831, Q4IBN1, Q4P965, Q4WJS2, Q5AI80, Q5BGC4, Q6BSL1, Q6CHK0, Q6CY29, Q6FM94, Q758Y4, Q7RZQ3, Q8VIG0, Q8WYQ9, Q9P6R7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	148
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
267475	Single allele	Pathogenic

SpliceAI

2734 predictions. Top by Δscore:

Variant	Effect	Δscore
16:87412972:CACAC:C	acceptor_gain	1.0000
16:87412973:ACACC:A	acceptor_loss	1.0000
16:87412974:CAC:C	acceptor_gain	1.0000
16:87412974:CACCT:C	acceptor_loss	1.0000
16:87412976:CCTAG:C	acceptor_loss	1.0000
16:87412977:C:CC	acceptor_gain	1.0000
16:87412977:CTAGA:C	acceptor_loss	1.0000
16:87412978:T:A	acceptor_loss	1.0000
16:87413053:A:AC	donor_gain	1.0000
16:87413054:C:CC	donor_gain	1.0000
16:87413054:CGT:C	donor_gain	1.0000
16:87413056:T:TA	donor_gain	1.0000
16:87415272:TCA:T	donor_loss	1.0000
16:87415273:CACTT:C	donor_loss	1.0000
16:87415274:A:AC	donor_gain	1.0000
16:87415274:A:T	donor_loss	1.0000
16:87415275:C:CA	donor_gain	1.0000
16:87415275:CTTTT:C	donor_gain	1.0000
16:87415367:ACT:A	acceptor_loss	1.0000
16:87415368:C:CA	acceptor_loss	1.0000
16:87415368:C:CC	acceptor_gain	1.0000
16:87415369:T:C	acceptor_gain	1.0000
16:87415372:C:CT	acceptor_gain	1.0000
16:87415374:C:CT	acceptor_gain	1.0000
16:87415375:A:T	acceptor_gain	1.0000
16:87418812:T:C	donor_gain	1.0000
16:87420015:T:TA	donor_gain	1.0000
16:87420601:CCTCA:C	donor_loss	1.0000
16:87420602:CTCAC:C	donor_loss	1.0000
16:87420603:TCA:T	donor_loss	1.0000

AlphaMissense

7091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:87410323:A:G	L936S	1.000
16:87411547:G:C	C921W	1.000
16:87411548:C:G	C921S	1.000
16:87411548:C:T	C921Y	1.000
16:87411549:A:G	C921R	1.000
16:87411549:A:T	C921S	1.000
16:87411564:G:C	H916D	1.000
16:87411577:G:C	C911W	1.000
16:87411578:C:A	C911F	1.000
16:87411578:C:G	C911S	1.000
16:87411578:C:T	C911Y	1.000
16:87411579:A:G	C911R	1.000
16:87411579:A:T	C911S	1.000
16:87411586:A:C	C908W	1.000
16:87411587:C:G	C908S	1.000
16:87411587:C:T	C908Y	1.000
16:87411588:A:G	C908R	1.000
16:87411588:A:T	C908S	1.000
16:87411948:A:G	C788R	1.000
16:87415282:A:G	L353P	1.000
16:87415288:A:G	L351P	1.000
16:87415288:A:T	L351Q	1.000
16:87415296:C:A	K348N	1.000
16:87415296:C:G	K348N	1.000
16:87415300:A:C	L347R	1.000
16:87415300:A:G	L347P	1.000
16:87415300:A:T	L347H	1.000
16:87415302:C:A	K346N	1.000
16:87415302:C:G	K346N	1.000
16:87415304:T:C	K346E	1.000

dbSNP variants (sampled 300 via entrez): RS1000043714 (16:87443383 A>G), RS1000072339 (16:87425950 A>C), RS1000093528 (16:87475094 G>C), RS1000108352 (16:87487687 T>A), RS1000117290 (16:87458889 A>C,G), RS1000205306 (16:87483474 G>A,T), RS1000212303 (16:87466825 T>C,G), RS1000227606 (16:87454754 T>A,C), RS1000234690 (16:87443012 C>T), RS1000282225 (16:87470494 G>A,C), RS1000286964 (16:87443158 G>C), RS1000299120 (16:87434870 A>G), RS1000328825 (16:87479117 T>C,G), RS1000335405 (16:87410766 G>A), RS1000363239 (16:87411010 T>C,G)

Disease associations

OMIM: gene MIM:620697 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): 16q24.3 microdeletion syndrome (MONDO:0016838)

Orphanet (1): 16q24.3 microdeletion syndrome (Orphanet:261250)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001469_5	Major depressive disorder	5.000000e-06
GCST003720_41	Migraine	3.000000e-09
GCST003986_12	Migraine	2.000000e-09
GCST004020_1	Small vessel stroke	3.000000e-09
GCST005232_16	Neuroticism	1.000000e-06
GCST007013_4	Hippocampal volume in mild cognitive impairment	8.000000e-07
GCST007257_15	Broad depression or schizophrenia	5.000000e-09
GCST010002_117	Refractive error	6.000000e-09
GCST012354_50	Anxiety	3.000000e-14
GCST90014122_4	Lacunar stroke	3.000000e-08
GCST90014123_4	Lacunar stroke	9.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:1001504	small vessel stroke
EFO:0007660	neuroticism measurement
EFO:0005035	hippocampal volume
EFO:0009863	anxiety measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Formaldehyde	decreases expression, increases expression	2
Hydrogen Peroxide	affects expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
quercitrin	increases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
nickel sulfate	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzene	increases expression	1
Carbamazepine	affects expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Vanadates	decreases expression	1

Clinical trials (associated diseases)

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