ZCCHC17

Summary

ZCCHC17 (zinc finger CCHC-type containing 17, HGNC:30246) is a protein-coding gene on chromosome 1p35.2, encoding Zinc finger CCHC domain-containing protein 17 (Q9NP64).

Enables identical protein binding activity. Predicted to be involved in RNA stabilization. Predicted to be located in nucleolus. Predicted to be part of cytosolic large ribosomal subunit.

Source: NCBI Gene 51538 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_016505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30246
Approved symbol	ZCCHC17
Name	zinc finger CCHC-type containing 17
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	PS1D, HSPC251, pNO40
Ensembl gene	ENSG00000121766
Ensembl biotype	protein_coding
OMIM	619744
Entrez	51538

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000344147, ENST00000373714, ENST00000479629, ENST00000546109, ENST00000615916, ENST00000616393, ENST00000616859, ENST00000618216, ENST00000627541, ENST00000863986, ENST00000863987, ENST00000863988, ENST00000863989, ENST00000863990, ENST00000863991, ENST00000915427, ENST00000915428, ENST00000915429, ENST00000969907

RefSeq mRNA: 10 — MANE Select: NM_016505 NM_001282566, NM_001282567, NM_001282568, NM_001282569, NM_001282570, NM_001282571, NM_001282572, NM_001282573, NM_001282574, NM_016505

CCDS: CCDS341, CCDS60061, CCDS60062, CCDS72741, CCDS72742, CCDS72743, CCDS72744

Canonical transcript exons

ENST00000344147 — 8 exons

Exon	Start	End
ENSE00000825250	31348829	31348974
ENSE00001049256	31297032	31297075
ENSE00001461371	31364032	31364936
ENSE00003474851	31319109	31319166
ENSE00003576361	31346640	31346740
ENSE00003600538	31338957	31339048
ENSE00003633426	31310044	31310164
ENSE00003639383	31337175	31337275

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.0335 / max 1736.7873, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1884	37.6013	1809
1883	1.4322	902

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.72	gold quality
spinal cord	UBERON:0002240	97.34	gold quality
hypothalamus	UBERON:0001898	95.98	gold quality
amygdala	UBERON:0001876	95.97	gold quality
anterior cingulate cortex	UBERON:0009835	95.76	gold quality
prefrontal cortex	UBERON:0000451	95.29	gold quality
right frontal lobe	UBERON:0002810	95.22	gold quality
substantia nigra	UBERON:0002038	94.98	gold quality
middle temporal gyrus	UBERON:0002771	94.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.73	gold quality
nucleus accumbens	UBERON:0001882	94.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.61	gold quality
right testis	UBERON:0004534	94.45	gold quality
midbrain	UBERON:0001891	94.37	gold quality
neocortex	UBERON:0001950	94.33	gold quality
frontal cortex	UBERON:0001870	94.32	gold quality
left testis	UBERON:0004533	94.07	gold quality
islet of Langerhans	UBERON:0000006	94.04	gold quality
monocyte	CL:0000576	94.01	gold quality
temporal lobe	UBERON:0001871	93.99	gold quality
cerebral cortex	UBERON:0000956	93.97	gold quality
leukocyte	CL:0000738	93.74	gold quality
Ammon’s horn	UBERON:0001954	93.72	gold quality
putamen	UBERON:0001874	93.57	gold quality
forebrain	UBERON:0001890	93.43	gold quality
heart left ventricle	UBERON:0002084	93.38	gold quality
testis	UBERON:0000473	93.35	gold quality
caudate nucleus	UBERON:0001873	93.35	gold quality
apex of heart	UBERON:0002098	93.23	gold quality
tibialis anterior	UBERON:0001385	93.20	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting ZCCHC17, 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-1252-5P	100.00	69.80	2774
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4267	99.96	66.53	2368
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-4503	99.85	71.45	1869
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3135B	98.61	65.33	1470

Literature-anchored findings (GeneRIF, showing 5)

• molecular cloning and characterization; it is localized to nucleoli of diverse cultured cells, with some concentration in the granular component of nucleoli (PMID:12893261)
• ZCCHC17 loss is an early driver of lower synaptic gene expression in Alzheimer’s disease. (PMID:29028963)
• These results demonstrate the role of pNO40 in ribosomal RNA biosynthesis regulation by compromising UBF function in ribosomal DNA transcription activation with subsequent ribosomal RNA synthesis inhibition. (PMID:31217076)
• ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer’s Disease. (PMID:38050142)
• ZCCHC17 knockdown phenocopies Alzheimer’s disease-related loss of synaptic proteins and hyperexcitability. (PMID:38630575)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zcchc17	ENSDARG00000018936
mus_musculus	Zcchc17	ENSMUSG00000028772
rattus_norvegicus	Zcchc17	ENSRNOG00000012266

Protein

Protein identifiers

Zinc finger CCHC domain-containing protein 17 — Q9NP64 (reviewed: Q9NP64)

Alternative names: Nucleolar protein of 40 kDa, Pnn-interacting nucleolar protein, Putative S1 RNA-binding domain protein

All UniProt accessions (6): A0A087WXF8, A0A087WXU5, A0A087WYF0, A0A087WYV3, A0A0D9SEW3, Q9NP64

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with PNN. Associates with the 60S ribosomal subunit.

Subcellular location. Nucleus. Nucleolus.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NP64-1	1, hpNO40	yes
Q9NP64-2	2, hpNO40s
Q9NP64-3	3

RefSeq proteins (10): NP_001269495, NP_001269496, NP_001269497, NP_001269498, NP_001269499, NP_001269500, NP_001269501, NP_001269502, NP_001269503, NP_057589* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR003029	S1_domain	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR047913	ZCCHC17_S1	Domain

Pfam: PF00575

UniProt features (22 total): strand 6, compositionally biased region 4, modified residue 3, splice variant 2, helix 2, chain 1, domain 1, sequence conflict 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CQO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP64-F1	70.38	0.28

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 (3): 183, 114, 144

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, LIAO_METASTASIS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, YYCATTCAWW_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME, GOCC_CYTOSOLIC_LARGE_RIBOSOMAL_SUBUNIT, chr1p35, GOCC_RIBOSOMAL_SUBUNIT, GOCC_NUCLEOLUS, GOCC_RIBONUCLEOPROTEIN_COMPLEX

GO Biological Process (1): RNA stabilization (GO:0043489)

GO Molecular Function (6): RNA binding (GO:0003723), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleolus (GO:0005730), cytosolic large ribosomal subunit (GO:0022625), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
regulation of RNA stability	1
negative regulation of RNA catabolic process	1
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
large ribosomal subunit	1
cytosolic ribosome	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2058 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZCCHC17	SCAF4	O95104	663
ZCCHC17	NCBP2	P52298	655
ZCCHC17	PNN	Q9H307	594
ZCCHC17	SF3B4	Q15427	561
ZCCHC17	TTC38	Q5R3I4	484
ZCCHC17	NKAIN1	Q4KMZ8	467
ZCCHC17	RRP8	O43159	458
ZCCHC17	SNRNP40	Q96DI7	446
ZCCHC17	KIF22	Q14807	442
ZCCHC17	SERINC2	Q96SA4	439
ZCCHC17	MAGED1	Q9Y5V3	433
ZCCHC17	ZWINT	O95229	426
ZCCHC17	AFAP1	Q8N556	409
ZCCHC17	TMEM70	Q9BUB7	387
ZCCHC17	TRAPPC13	A5PLN9	386

IntAct

130 interactions, top by confidence:

A	B	Type	Score
SDCBP2	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.830
ZCCHC17	SDCBP2	psi-mi:“MI:0915”(physical association)	0.830
SDCBP	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.720
ZCCHC17	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
JMJD6	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.630
ZCCHC17	JMJD6	psi-mi:“MI:0915”(physical association)	0.630
	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
ZCCHC17		psi-mi:“MI:0915”(physical association)	0.560
AP1M1	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
LXN	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
ZCCHC17	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
ZNF16	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
SHTN1	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
EHHADH	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
RNF4	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
ZCCHC17	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560
ZCCHC17	GSN	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (147): ZCCHC17 (Two-hybrid), ZCCHC17 (Two-hybrid), ZCCHC17 (Two-hybrid), ZCCHC17 (Affinity Capture-MS), ZCCHC17 (Two-hybrid), ZCCHC17 (Reconstituted Complex), ZCCHC17 (Biochemical Activity), ZCCHC17 (Two-hybrid), ZCCHC17 (Affinity Capture-MS), ZCCHC17 (Affinity Capture-MS), ZCCHC17 (Affinity Capture-MS), ZCCHC17 (Affinity Capture-MS), ZCCHC17 (Affinity Capture-MS), ZCCHC17 (Affinity Capture-MS), ZCCHC17 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9L3, A8WT19, A8X8D0, G5EEW6, O15042, P0C196, P0C1I6, P0C1I9, P0C1J2, P0CP88, P0CP89, P30189, P34498, P52016, Q02770, Q08C72, Q09637, Q10988, Q17336, Q17QX9, Q17R09, Q19375, Q23357, Q23462, Q26548, Q2U256, Q4IE79, Q4WAQ9, Q5ARI5, Q5R7X2, Q5RBG4, Q5XIB2, Q6C8C5, Q6CC11, Q6GLX7, Q6NV83, Q6Q151, Q6Q152, Q7ZW86, Q871A4

Diamond homologs: A1Z9L3, A2A4P0, A3KMI0, A8LKE7, B4PRJ9, D4A2Z8, F4HYJ7, F4IE66, F4IJV4, F4ILR7, F4IM84, F4JMJ3, F4JRJ6, F4K2E9, F4KGU4, O17438, O22243, O22899, O35286, O42643, O42945, O43143, O45244, O46072, O51767, O60231, O70133, P0C7L7, P0CE10, P15938, P20095, P24384, P34498, P36009, P37024, P43329, P45018, P53131, Q03319, Q04217

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 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
Response of EIF2AK4 (GCN2) to amino acid deficiency	7	13.4×	3e-04
Peptide chain elongation	6	13.1×	3e-04
Viral mRNA Translation	6	13.1×	3e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	6	13.0×	3e-04
Selenocysteine synthesis	6	12.4×	3e-04
Eukaryotic Translation Termination	6	12.4×	3e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	6	12.2×	3e-04
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	6	12.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	7	15.6×	2e-04
translation	7	8.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1847 predictions. Top by Δscore:

Variant	Effect	Δscore
1:31318237:GTAT:G	donor_gain	1.0000
1:31338951:TTTCA:T	acceptor_loss	1.0000
1:31338952:TTCAG:T	acceptor_loss	1.0000
1:31338953:TCAGA:T	acceptor_loss	1.0000
1:31338954:CAGA:C	acceptor_loss	1.0000
1:31338955:A:AG	acceptor_gain	1.0000
1:31338955:A:C	acceptor_loss	1.0000
1:31338956:G:GC	acceptor_loss	1.0000
1:31338956:G:GG	acceptor_gain	1.0000
1:31339045:TTGA:T	donor_gain	1.0000
1:31339046:TGA:T	donor_gain	1.0000
1:31339046:TGAGT:T	donor_loss	1.0000
1:31339047:GA:G	donor_gain	1.0000
1:31339047:GAG:G	donor_gain	1.0000
1:31339048:AGTAA:A	donor_loss	1.0000
1:31339049:G:GG	donor_gain	1.0000
1:31339049:G:T	donor_loss	1.0000
1:31339050:T:TG	donor_loss	1.0000
1:31339051:AAGT:A	donor_loss	1.0000
1:31339052:AGTAA:A	donor_loss	1.0000
1:31348825:GCAG:G	acceptor_loss	1.0000
1:31348826:CAGGC:C	acceptor_loss	1.0000
1:31348827:A:C	acceptor_loss	1.0000
1:31348828:G:A	acceptor_loss	1.0000
1:31348828:GGCC:G	acceptor_gain	1.0000
1:31348971:GAAG:G	donor_gain	1.0000
1:31348972:A:T	donor_gain	1.0000
1:31348972:AAG:A	donor_loss	1.0000
1:31348973:AGGTG:A	donor_loss	1.0000
1:31348975:G:GA	donor_loss	1.0000

AlphaMissense

1607 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:31310159:G:A	G21R	1.000
1:31310159:G:C	G21R	1.000
1:31310160:G:A	G21E	1.000
1:31319109:G:T	V23F	1.000
1:31319110:T:A	V23D	1.000
1:31319130:G:A	G30R	1.000
1:31319130:G:C	G30R	1.000
1:31319130:G:T	G30W	1.000
1:31319131:G:A	G30E	1.000
1:31319131:G:T	G30V	1.000
1:31319134:C:A	A31D	1.000
1:31319136:T:C	F32L	1.000
1:31319137:T:C	F32S	1.000
1:31319137:T:G	F32C	1.000
1:31319138:T:A	F32L	1.000
1:31319138:T:G	F32L	1.000
1:31319140:T:A	I33N	1.000
1:31319146:T:C	I35T	1.000
1:31319166:G:C	G42R	1.000
1:31337175:G:A	G42D	1.000
1:31337178:T:A	L43Q	1.000
1:31337178:T:C	L43P	1.000
1:31337181:T:A	V44D	1.000
1:31337183:C:A	H45N	1.000
1:31337183:C:G	H45D	1.000
1:31337184:A:G	H45R	1.000
1:31337185:T:A	H45Q	1.000
1:31337185:T:G	H45Q	1.000
1:31337196:T:A	M49K	1.000
1:31337196:T:G	M49R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006199 (1:31316760 G>C), RS1000045127 (1:31335949 T>G), RS1000059919 (1:31324898 T>C), RS1000154651 (1:31329822 T>A), RS1000177397 (1:31299548 G>A,C), RS1000221964 (1:31305445 A>C), RS1000310520 (1:31318470 A>C), RS1000319491 (1:31335569 G>A,T), RS1000353599 (1:31311726 G>A,C,T), RS1000383067 (1:31311442 A>C,G), RS1000417490 (1:31299318 G>C), RS1000511552 (1:31298160 T>C), RS1000528279 (1:31331417 A>T), RS1000550071 (1:31352717 G>A,T), RS1000604100 (1:31334438 A>T)

Disease associations

OMIM: gene MIM:619744 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001874_1	Alcohol dependence	3.000000e-08
GCST005769_2	Body mass index	9.000000e-06
GCST005951_36	Body mass index	9.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression, affects cotreatment, increases expression	3
Valproic Acid	affects expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
titanium dioxide	decreases expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects 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, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects splicing	1
Ribonucleotides	affects binding	1
Silicon Dioxide	decreases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2LN	Abcam HeLa ZCCHC17 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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