ZC3H6

Summary

ZC3H6 (zinc finger CCCH-type containing 6, HGNC:24762) is a protein-coding gene on chromosome 2q14.1, encoding Zinc finger CCCH domain-containing protein 6 (P61129).

Predicted to enable RNA binding activity and zinc ion binding activity. Predicted to be involved in negative regulation of DNA-templated transcription. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 376940 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 162 total — 1 likely-pathogenic
• MANE Select transcript: NM_198581

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24762
Approved symbol	ZC3H6
Name	zinc finger CCCH-type containing 6
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ41410, FLJ45877, KIAA2035
Ensembl gene	ENSG00000188177
Ensembl biotype	protein_coding
Entrez	376940

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000409871, ENST00000476511, ENST00000502881, ENST00000968137

RefSeq mRNA: 1 — MANE Select: NM_198581 NM_198581

CCDS: CCDS46393

Canonical transcript exons

ENST00000409871 — 12 exons

Exon	Start	End
ENSE00001374726	112311804	112311937
ENSE00001380934	112324152	112324663
ENSE00001382732	112316470	112316586
ENSE00001383423	112322649	112322902
ENSE00001388099	112324964	112325197
ENSE00001418378	112299849	112300029
ENSE00001577131	112321756	112321865
ENSE00001579327	112331005	112340059
ENSE00001587381	112275597	112276026
ENSE00002536496	112317221	112317332
ENSE00003547401	112303229	112303351
ENSE00003577708	112309885	112310161

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 96.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8460 / max 2116.6920, expressed in 1779 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21976	11.4596	1748
21978	2.1284	399
21975	1.6495	877
21980	1.2060	268
21979	0.2491	66
21977	0.1533	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.56	gold quality
sural nerve	UBERON:0015488	95.15	gold quality
tendon	UBERON:0000043	93.30	gold quality
tendon of biceps brachii	UBERON:0008188	91.78	silver quality
oviduct epithelium	UBERON:0004804	89.77	gold quality
buccal mucosa cell	CL:0002336	89.05	gold quality
corpus callosum	UBERON:0002336	87.93	gold quality
monocyte	CL:0000576	86.41	gold quality
colonic epithelium	UBERON:0000397	86.17	gold quality
epithelial cell of pancreas	CL:0000083	85.56	silver quality
leukocyte	CL:0000738	85.48	gold quality
left ventricle myocardium	UBERON:0006566	85.16	gold quality
quadriceps femoris	UBERON:0001377	84.38	silver quality
deltoid	UBERON:0001476	84.35	silver quality
vastus lateralis	UBERON:0001379	84.23	silver quality
caput epididymis	UBERON:0004358	83.67	gold quality
medial globus pallidus	UBERON:0002477	83.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.21	silver quality
tibialis anterior	UBERON:0001385	82.84	silver quality
corpus epididymis	UBERON:0004359	82.52	gold quality
skeletal muscle tissue	UBERON:0001134	82.33	gold quality
globus pallidus	UBERON:0001875	81.76	gold quality
cerebellar vermis	UBERON:0004720	81.74	gold quality
muscle tissue	UBERON:0002385	81.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.93	gold quality
cortical plate	UBERON:0005343	80.53	gold quality
upper arm skin	UBERON:0004263	80.43	silver quality
layer of synovial tissue	UBERON:0007616	80.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94
E-GEOD-111727	no	172.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

319 targeting ZC3H6, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
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-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-1184	99.99	68.19	1458

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zc3h6	ENSDARG00000075165
mus_musculus	Zc3h6	ENSMUSG00000042851
rattus_norvegicus	Zc3h6	ENSRNOG00000026277

Paralogs (2): ZC3H4 (ENSG00000130749), ZC3H8 (ENSG00000144161)

Protein

Protein identifiers

Zinc finger CCCH domain-containing protein 6 — P61129 (reviewed: P61129)

All UniProt accessions (1): P61129

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (1): NP_940983* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR045124	Su(sable)-like	Family
IPR054361	Znf-CCCH_ZC3H4/6/8	Domain

Pfam: PF00642, PF18345, PF22623

UniProt features (26 total): compositionally biased region 12, region of interest 6, zinc finger region 3, coiled-coil region 2, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61129-F1	51.45	0.01

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): 1158

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): AAGCAAT_MIR137, FREAC4_01, ATCATGA_MIR433, FOXJ2_02, GOBP_NEGATIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, chr2q14, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, OSMAN_BLADDER_CANCER_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, CAGTATT_MIR200B_MIR200C_MIR429, GOBP_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, BRUINS_UVC_RESPONSE_EARLY_LATE

GO Biological Process (1): negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (3): RNA binding (GO:0003723), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZC3H6	TMEM87B	Q96K49	565
ZC3H6	FBLN7	Q53RD9	513
ZC3H6	MBLAC1	A4D2B0	479
ZC3H6	ANAPC1	Q9H1A4	453
ZC3H6	ACOXL	Q9NUZ1	451
ZC3H6	ATOSA	Q32MH5	432
ZC3H6	KBTBD4	Q9NVX7	425
ZC3H6	ZBTB47	Q9UFB7	421
ZC3H6	RBM12	Q9NTZ6	417
ZC3H6	GPR156	Q8NFN8	404
ZC3H6	UBAP2L	Q14157	403
ZC3H6	KIAA0232	Q92628	393
ZC3H6	NUDT21	O43809	391
ZC3H6	ISG20L2	Q9H9L3	391
ZC3H6	ZNF598	Q86UK7	387

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ZC3H6	H1-2	psi-mi:“MI:0915”(physical association)	0.400
ZNF346	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): ZC3H6 (Affinity Capture-MS), ZC3H6 (Affinity Capture-RNA), ZC3H6 (Proximity Label-MS), ZC3H6 (Affinity Capture-MS), ZC3H4 (Negative Genetic), ZC3H6 (Co-fractionation), UBE2L3 (Co-fractionation), ZC3H6 (Affinity Capture-MS), ZC3H6 (Affinity Capture-MS), ZC3H6 (Cross-Linking-MS (XL-MS)), ZC3H6 (Cross-Linking-MS (XL-MS)), ZC3H6 (Proximity Label-MS), ZC3H6 (Proximity Label-MS), ZC3H6 (Proximity Label-MS), ZC3H6 (Affinity Capture-MS)

ESM2 similar proteins: A0JLT2, A4QNZ7, A5PK23, B1AZP2, F5HSE3, O60293, O75420, O95402, P61129, P78312, P97839, Q03111, Q07FY3, Q08C81, Q08DM1, Q174D3, Q1LVC2, Q32NP7, Q3T044, Q4G0F8, Q5EAY2, Q5F368, Q5R8Q8, Q5U2R6, Q6DD45, Q6DRL8, Q6PEI3, Q7TN02, Q80Z38, Q8C1B1, Q8C1S0, Q8CFT2, Q8CGI1, Q8IVL1, Q8K4J6, Q90YL3, Q90YY5, Q969V6, Q96A73, Q99MR1

Diamond homologs: P61129, Q6ZPZ3, Q8BYK8, Q8N5P1, Q9JJ48, Q9UPT8, Q9LTS7, P22293

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	142
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
983183	GRCh37/hg19 2q13(chr2:111368818-113065741)x3	Likely pathogenic

SpliceAI

2279 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112299845:A:AG	acceptor_gain	1.0000
2:112299845:ATAG:A	acceptor_loss	1.0000
2:112299846:T:G	acceptor_gain	1.0000
2:112299846:TA:T	acceptor_loss	1.0000
2:112299847:A:AG	acceptor_gain	1.0000
2:112299847:A:AT	acceptor_loss	1.0000
2:112299848:G:GT	acceptor_gain	1.0000
2:112299848:GA:G	acceptor_gain	1.0000
2:112299848:GAGA:G	acceptor_gain	1.0000
2:112299848:GAGAA:G	acceptor_gain	1.0000
2:112300030:G:GG	donor_gain	1.0000
2:112303227:A:AG	acceptor_gain	1.0000
2:112303228:G:GA	acceptor_gain	1.0000
2:112303228:GC:G	acceptor_gain	1.0000
2:112303228:GCAT:G	acceptor_gain	1.0000
2:112303228:GCATA:G	acceptor_gain	1.0000
2:112303327:GGAT:G	donor_gain	1.0000
2:112303347:CTCAG:C	donor_loss	1.0000
2:112303348:TCAG:T	donor_loss	1.0000
2:112303349:CAGGT:C	donor_loss	1.0000
2:112303350:AGGTA:A	donor_loss	1.0000
2:112303351:GG:G	donor_loss	1.0000
2:112303352:G:A	donor_loss	1.0000
2:112303353:T:A	donor_loss	1.0000
2:112311900:GGCC:G	donor_gain	1.0000
2:112311933:AAGAG:A	donor_loss	1.0000
2:112311935:G:GT	donor_gain	1.0000
2:112311935:GAG:G	donor_gain	1.0000
2:112311935:GAGG:G	donor_loss	1.0000
2:112311936:AGG:A	donor_loss	1.0000

AlphaMissense

7869 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112316512:T:C	F264L	1.000
2:112316513:T:C	F264S	1.000
2:112316513:T:G	F264C	1.000
2:112316514:T:A	F264L	1.000
2:112316514:T:G	F264L	1.000
2:112316524:C:G	H268D	1.000
2:112316554:T:A	C278S	1.000
2:112316554:T:C	C278R	1.000
2:112316555:G:A	C278Y	1.000
2:112316555:G:C	C278S	1.000
2:112316555:G:T	C278F	1.000
2:112316556:T:G	C278W	1.000
2:112316578:T:A	C286S	1.000
2:112316578:T:C	C286R	1.000
2:112316579:G:A	C286Y	1.000
2:112316579:G:C	C286S	1.000
2:112316579:G:T	C286F	1.000
2:112316580:T:G	C286W	1.000
2:112317230:T:A	C292S	1.000
2:112317230:T:C	C292R	1.000
2:112317231:G:A	C292Y	1.000
2:112317231:G:C	C292S	1.000
2:112317231:G:T	C292F	1.000
2:112317232:T:G	C292W	1.000
2:112317236:T:C	F294L	1.000
2:112317237:T:C	F294S	1.000
2:112317237:T:G	F294C	1.000
2:112317238:T:A	F294L	1.000
2:112317238:T:G	F294L	1.000
2:112317275:T:C	C307R	1.000

dbSNP variants (sampled 300 via entrez): RS1000030607 (2:112334133 C>A,T), RS1000032458 (2:112322138 T>C), RS1000106904 (2:112315705 C>T), RS1000162154 (2:112300691 T>G), RS1000217529 (2:112326962 A>C), RS1000240581 (2:112327249 G>A), RS1000283846 (2:112308301 C>T), RS1000315514 (2:112323824 A>G), RS1000354342 (2:112294303 A>T), RS1000516974 (2:112328303 G>A), RS1000548663 (2:112278799 G>A), RS1000631608 (2:112310230 A>G), RS1000680736 (2:112274002 T>C), RS1000717688 (2:112308587 C>G), RS1000728606 (2:112302409 T>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
entinostat	decreases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
OTX015	increases expression	1
FR900359	increases phosphorylation	1
mivebresib	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
dinophysistoxin 1	decreases expression	1
phenethyl isothiocyanate	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Panobinostat	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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