ZCCHC2

Summary

ZCCHC2 (zinc finger CCHC-type containing 2, HGNC:22916) is a protein-coding gene on chromosome 18q21.33, encoding Zinc finger CCHC domain-containing protein 2 (Q9C0B9).

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

Source: NCBI Gene 54877 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 210 total
• MANE Select transcript: NM_017742

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22916
Approved symbol	ZCCHC2
Name	zinc finger CCHC-type containing 2
Location	18q21.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20281, KIAA1744, FLJ20222
Ensembl gene	ENSG00000141664
Ensembl biotype	protein_coding
OMIM	620095
Entrez	54877

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000269499, ENST00000585873, ENST00000585949, ENST00000586834, ENST00000587612, ENST00000588676, ENST00000590840, ENST00000591145, ENST00000591435, ENST00000591632, ENST00000621048, ENST00000963441

RefSeq mRNA: 1 — MANE Select: NM_017742 NM_017742

CCDS: CCDS45880

Canonical transcript exons

ENST00000269499 — 14 exons

Exon	Start	End
ENSE00000950339	62544802	62544873
ENSE00000950341	62556203	62556297
ENSE00000950342	62558687	62558770
ENSE00002841411	62576512	62578579
ENSE00002891025	62523025	62524363
ENSE00003527022	62564571	62564635
ENSE00003567939	62565002	62565096
ENSE00003588026	62539681	62539792
ENSE00003589621	62550348	62550460
ENSE00003635855	62542498	62542574
ENSE00003648830	62563009	62563144
ENSE00003682027	62570103	62570231
ENSE00003682612	62574057	62575550
ENSE00003791469	62560587	62560644

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0092 / max 405.4219, expressed in 1750 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170526	8.6139	1656
170529	1.6169	813
170530	1.2677	571
170527	1.0205	597
170531	0.8011	307
170532	0.4101	17
170528	0.1410	55
170534	0.1100	30
170533	0.0281	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.30	gold quality
oocyte	CL:0000023	94.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.56	gold quality
cauda epididymis	UBERON:0004360	90.84	gold quality
gastrocnemius	UBERON:0001388	90.69	gold quality
visceral pleura	UBERON:0002401	90.25	gold quality
right lobe of liver	UBERON:0001114	90.15	gold quality
caput epididymis	UBERON:0004358	90.12	gold quality
popliteal artery	UBERON:0002250	90.03	gold quality
tibial artery	UBERON:0007610	90.02	gold quality
muscle of leg	UBERON:0001383	89.88	gold quality
corpus epididymis	UBERON:0004359	89.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.55	gold quality
endothelial cell	CL:0000115	89.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.41	gold quality
right testis	UBERON:0004534	88.37	gold quality
testis	UBERON:0000473	88.10	gold quality
adrenal tissue	UBERON:0018303	88.09	gold quality
aorta	UBERON:0000947	88.06	gold quality
trabecular bone tissue	UBERON:0002483	87.97	gold quality
left testis	UBERON:0004533	87.94	gold quality
skin of hip	UBERON:0001554	87.90	gold quality
calcaneal tendon	UBERON:0003701	87.83	gold quality
liver	UBERON:0002107	87.72	gold quality
pleura	UBERON:0000977	87.42	gold quality
blood	UBERON:0000178	87.27	gold quality
colonic epithelium	UBERON:0000397	87.18	gold quality
skin of leg	UBERON:0001511	87.03	gold quality
lower lobe of lung	UBERON:0008949	86.59	gold quality
skin of abdomen	UBERON:0001416	86.54	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.38
E-GEOD-75367	no	137.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

202 targeting ZCCHC2, 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-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-9-3P	99.96	70.88	2068

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zcchc2	ENSDARG00000067950
mus_musculus	Zcchc2	ENSMUSG00000038866
rattus_norvegicus	Zcchc2	ENSRNOG00000002882
drosophila_melanogaster	CG10492	FBGN0032748
caenorhabditis_elegans	gls-1	WBGENE00007975

Paralogs (1): ZCCHC14 (ENSG00000140948)

Protein

Protein identifiers

Zinc finger CCHC domain-containing protein 2 — Q9C0B9 (reviewed: Q9C0B9)

All UniProt accessions (5): A0A087WXC7, Q9C0B9, K7EKB8, K7ERQ9, K7ESN2

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C0B9-1	1	yes
Q9C0B9-2	2

RefSeq proteins (1): NP_060212* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR036871	PX_dom_sf	Homologous_superfamily
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR042793	ZCCHC2	Family
IPR057327	Vts1_dom	Domain
IPR058599	PHAT_Smg/ZCCHC2-like	Domain

Pfam: PF00098, PF25479, PF26034

UniProt features (23 total): compositionally biased region 12, region of interest 4, sequence conflict 2, chain 1, zinc finger region 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0B9-F1	49.91	0.11

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): 236

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 241 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, ATGCAGT_MIR217, CTATGCA_MIR153, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, TATCTGG_MIR488, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, PASQUALUCCI_LYMPHOMA_BY_GC_STAGE_DN, KIM_WT1_TARGETS_DN, GOMF_PHOSPHATIDYLINOSITOL_BINDING, HAMAI_APOPTOSIS_VIA_TRAIL_UP, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING

GO Biological Process (0):

GO Molecular Function (4): nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), phosphatidylinositol binding (GO:0035091), 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
binding	1
transition metal ion binding	1
anion binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZCCHC2	RELCH	Q9P260	666
ZCCHC2	ZNF518A	Q6AHZ1	559
ZCCHC2	NKAPD1	Q6ZUT1	482
ZCCHC2	ZNF891	A8MT65	473
ZCCHC2	CYLC2	Q14093	461
ZCCHC2	TMEM150B	A6NC51	421
ZCCHC2	PHLPP1	O60346	410
ZCCHC2	USP38	Q8NB14	379
ZCCHC2	TEX35	Q5T0J7	377
ZCCHC2	DNAJC13	O75165	376
ZCCHC2	FBXO16	Q8IX29	374
ZCCHC2	OR11G2	Q8NGC1	369
ZCCHC2	FAM47A	Q5JRC9	368
ZCCHC2	N4BP1	O75113	363
ZCCHC2	LYSMD2	Q8IV50	360

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ZCCHC2	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
RMND5A	HTRA2	psi-mi:“MI:0914”(association)	0.350
ARRDC2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
ARRDC3	ESYT2	psi-mi:“MI:0914”(association)	0.350
TXNIP	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
ARMC8	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): ZCCHC2 (Affinity Capture-MS), ZCCHC2 (Affinity Capture-RNA), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Proximity Label-MS), ZCCHC2 (Affinity Capture-RNA), ZCCHC2 (Affinity Capture-Western), MYC (Affinity Capture-Western), ZCCHC2 (Affinity Capture-Western)

ESM2 similar proteins: A0JNG6, A2AKB4, A7YWL5, B0BN13, O35181, O43734, O70142, O70240, O88286, O88566, P0DPB3, P0DPB4, P56975, P70298, P86174, P97303, Q00IB7, Q1LY51, Q2M3C6, Q2T9L4, Q3TY60, Q498S6, Q4V7B1, Q568Z1, Q5HZN9, Q5JTD0, Q5SYB0, Q5U5E5, Q5VT97, Q69ZB8, Q6PG95, Q6UXB0, Q6ZU67, Q76N89, Q80YE4, Q86XD5, Q8BWU3, Q8BZB3, Q8CD60, Q8N365

Diamond homologs: Q498S6, Q69ZB8, Q9C0B9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	184
Likely benign	16
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2387 predictions. Top by Δscore:

Variant	Effect	Δscore
18:62539675:A:AG	acceptor_gain	1.0000
18:62539676:T:G	acceptor_gain	1.0000
18:62539676:TCTA:T	acceptor_loss	1.0000
18:62539677:CTA:C	acceptor_loss	1.0000
18:62539679:A:AG	acceptor_gain	1.0000
18:62539679:AG:A	acceptor_loss	1.0000
18:62539680:G:GG	acceptor_gain	1.0000
18:62539680:GA:G	acceptor_gain	1.0000
18:62539680:GAA:G	acceptor_gain	1.0000
18:62539680:GAAC:G	acceptor_gain	1.0000
18:62539680:GAACA:G	acceptor_gain	1.0000
18:62539789:GAAG:G	donor_gain	1.0000
18:62539794:T:G	donor_loss	1.0000
18:62542492:TTTCA:T	acceptor_loss	1.0000
18:62542493:TTCA:T	acceptor_loss	1.0000
18:62542495:CAGCT:C	acceptor_loss	1.0000
18:62542496:A:AG	acceptor_gain	1.0000
18:62542496:AGCT:A	acceptor_gain	1.0000
18:62542496:AGCTG:A	acceptor_loss	1.0000
18:62542497:G:GT	acceptor_gain	1.0000
18:62542497:GC:G	acceptor_gain	1.0000
18:62542497:GCT:G	acceptor_gain	1.0000
18:62542497:GCTG:G	acceptor_gain	1.0000
18:62542497:GCTGT:G	acceptor_gain	1.0000
18:62542559:G:GT	donor_gain	1.0000
18:62542559:G:T	donor_gain	1.0000
18:62542574:AG:A	donor_loss	1.0000
18:62542575:G:GG	donor_gain	1.0000
18:62542575:G:T	donor_loss	1.0000
18:62542576:T:A	donor_loss	1.0000

AlphaMissense

7621 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:62523777:T:C	L118P	1.000
18:62523780:T:C	L119P	1.000
18:62523786:T:C	L121P	1.000
18:62523790:C:G	C122W	1.000
18:62523800:G:A	E126K	1.000
18:62523804:T:C	L127P	1.000
18:62523806:C:A	R128S	1.000
18:62523809:T:C	F129L	1.000
18:62523810:T:C	F129S	1.000
18:62523811:C:A	F129L	1.000
18:62523811:C:G	F129L	1.000
18:62523813:T:C	L130P	1.000
18:62523815:G:C	G131R	1.000
18:62523816:G:A	G131D	1.000
18:62523825:T:C	L134P	1.000
18:62523834:T:C	L137P	1.000
18:62523846:A:T	D141V	1.000
18:62523858:T:C	L145P	1.000
18:62523960:T:C	L179P	1.000
18:62523987:C:A	A188D	1.000
18:62524236:C:A	A271D	1.000
18:62524239:T:C	F272S	1.000
18:62524244:T:C	F274L	1.000
18:62524246:C:A	F274L	1.000
18:62524246:C:G	F274L	1.000
18:62575478:T:A	C1133S	1.000
18:62575478:T:C	C1133R	1.000
18:62575479:G:A	C1133Y	1.000
18:62575479:G:C	C1133S	1.000
18:62575480:T:G	C1133W	1.000

dbSNP variants (sampled 300 via entrez): RS1000073892 (18:62557257 G>C), RS1000205490 (18:62546408 C>A,G), RS1000225876 (18:62563950 C>T), RS1000375615 (18:62582511 C>G), RS1000380159 (18:62540188 T>A), RS1000448872 (18:62525029 T>G), RS1000486643 (18:62534756 C>G), RS1000492720 (18:62546093 G>A), RS1000560115 (18:62562556 C>T), RS1000582363 (18:62583699 G>A), RS1000592729 (18:62562766 C>A,T), RS1000628389 (18:62555445 A>G,T), RS1000695073 (18:62557041 A>G,T), RS1000716705 (18:62541682 T>A), RS1000727264 (18:62582085 A>G)

Disease associations

OMIM: gene MIM:620095 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001699_10	Serum albumin levels	4.000000e-09
GCST001699_16	Serum albumin levels	1.000000e-08
GCST002715_3	Breastfeeding duration	1.000000e-06
GCST005863_30	Menopause (age at onset)	2.000000e-08
GCST005863_34	Menopause (age at onset)	1.000000e-08
GCST006629_15	Pulse pressure	1.000000e-10
GCST007565_32	Morning person	1.000000e-13
GCST007576_76	Chronotype	1.000000e-13
GCST007994_22	Asthma (age of onset)	2.000000e-10
GCST007995_6	Asthma (childhood onset)	9.000000e-09
GCST008103_29	Bipolar disorder	4.000000e-08
GCST011102_21	Bipolar disorder	1.000000e-08
GCST012170_5	Cognitive function in longevity	2.000000e-06
GCST012226_138	Waist circumference adjusted for body mass index	5.000000e-10
GCST012231_146	A body shape index	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006864	breastfeeding duration
EFO:0004704	age at menopause
EFO:0005763	pulse pressure measurement
EFO:0008328	chronotype measurement
EFO:0008354	cognitive function measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, decreases expression, increases expression	4
Formaldehyde	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, decreases expression	2
Magnetite Nanoparticles	increases methylation, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
ethylbenzene	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	decreases reaction, affects binding	1
butyraldehyde	decreases expression	1
2-xylene	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
dimethylarsinous acid	increases expression	1
(+)-JQ1 compound	increases expression	1
Bortezomib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Succimer	affects cotreatment, 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_B1II	Abcam A-549 ZCCHC2 KO 2	Cancer cell line	Male
CVCL_B2R1	Abcam A-549 ZCCHC2 KO 1	Cancer cell line	Male

Clinical trials (associated diseases)

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