CNBP

Summary

CNBP (CCHC-type zinc finger nucleic acid binding protein, HGNC:13164) is a protein-coding gene on chromosome 3q21.3, encoding CCHC-type zinc finger nucleic acid binding protein (P62633). Single-stranded DNA-binding protein that preferentially binds to the sterol regulatory element (SRE) sequence 5’-GTGCGGTG-3’, and thereby mediates transcriptional repression.

This gene encodes a nucleic-acid binding protein with seven zinc-finger domains. The protein has a preference for binding single stranded DNA and RNA. The protein functions in cap-independent translation of ornithine decarboxylase mRNA, and may also function in sterol-mediated transcriptional regulation. A CCTG expansion from <30 repeats to 75-11000 repeats in the first intron of this gene results in myotonic dystrophy type 2. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7555 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myotonic dystrophy type 2 (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 30 total — 1 pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes
• Transcription factor: yes — 27 downstream targets (CollecTRI)
• MANE Select transcript: NM_003418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13164
Approved symbol	CNBP
Name	CCHC-type zinc finger nucleic acid binding protein
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	RNF163, ZCCHC22, CNBP1
Ensembl gene	ENSG00000169714
Ensembl biotype	protein_coding
OMIM	116955
Entrez	7555

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 52 protein_coding, 2 retained_intron

ENST00000422453, ENST00000441626, ENST00000446936, ENST00000451728, ENST00000500450, ENST00000502372, ENST00000502976, ENST00000504813, ENST00000507573, ENST00000512338, ENST00000911019, ENST00000911020, ENST00000911021, ENST00000911022, ENST00000911023, ENST00000911024, ENST00000911025, ENST00000911026, ENST00000911027, ENST00000911028, ENST00000911029, ENST00000911030, ENST00000911031, ENST00000911032, ENST00000911033, ENST00000911034, ENST00000911035, ENST00000911036, ENST00000911037, ENST00000932128, ENST00000932129, ENST00000932130, ENST00000932131, ENST00000932132, ENST00000932133, ENST00000932134, ENST00000932135, ENST00000932136, ENST00000932137, ENST00000932138, ENST00000932139, ENST00000932140, ENST00000932141, ENST00000932142, ENST00000951528, ENST00000951529, ENST00000951530, ENST00000951531, ENST00000951532, ENST00000951533, ENST00000951534, ENST00000951535, ENST00000951536, ENST00000951537

RefSeq mRNA: 6 — MANE Select: NM_003418 NM_001127192, NM_001127193, NM_001127194, NM_001127195, NM_001127196, NM_003418

CCDS: CCDS3056, CCDS46906, CCDS46907, CCDS46908, CCDS54637

Canonical transcript exons

ENST00000422453 — 5 exons

Exon	Start	End
ENSE00000000359	129167827	129170570
ENSE00001177175	129171079	129171277
ENSE00001177178	129171446	129171538
ENSE00003593276	129171634	129171771
ENSE00003903298	129183776	129183896

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 197.5606 / max 1189.8397, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44500	138.9844	1826
44501	29.8073	1808
44499	17.6219	1792
44498	9.7982	1742
44494	1.3488	798

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.80	gold quality
diaphragm	UBERON:0001103	99.69	gold quality
biceps brachii	UBERON:0001507	99.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.68	gold quality
oocyte	CL:0000023	99.64	gold quality
calcaneal tendon	UBERON:0003701	99.63	gold quality
tendon	UBERON:0000043	99.60	gold quality
seminal vesicle	UBERON:0000998	99.51	gold quality
gastrocnemius	UBERON:0001388	99.51	gold quality
muscle of leg	UBERON:0001383	99.49	gold quality
parotid gland	UBERON:0001831	99.49	gold quality
cauda epididymis	UBERON:0004360	99.49	gold quality
heart right ventricle	UBERON:0002080	99.47	gold quality
ventricular zone	UBERON:0003053	99.46	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.45	gold quality
germinal epithelium of ovary	UBERON:0001304	99.43	gold quality
type B pancreatic cell	CL:0000169	99.42	gold quality
amniotic fluid	UBERON:0000173	99.42	gold quality
superficial temporal artery	UBERON:0001614	99.41	gold quality
epithelium of nasopharynx	UBERON:0001951	99.41	gold quality
tendon of biceps brachii	UBERON:0008188	99.41	gold quality
caput epididymis	UBERON:0004358	99.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.38	gold quality
left ovary	UBERON:0002119	99.36	gold quality
body of pancreas	UBERON:0001150	99.32	gold quality
muscle organ	UBERON:0001630	99.32	gold quality
right lung	UBERON:0002167	99.32	gold quality
embryo	UBERON:0000922	99.30	gold quality
penis	UBERON:0000989	99.30	gold quality
lower lobe of lung	UBERON:0008949	99.30	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	20.43
E-HCAD-11	yes	7.43
E-GEOD-124858	no	490.35
E-GEOD-93593	no	13.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

27 targets.

Target	Regulation
ACTB
ADIPOQ
CYP51A1
CYP8B1
DMPK
FAS
FASN
FDPS
HMGCR
HMGCS2
HNRNPK
IDE
LDLR
LIPC
LPL
LRP1
MTTP
MYC	Unknown
OMD
PARK7
PDX1
RPS6
SCAP
SLC2A4
STAR
THRAP3
WNT5B

Upstream regulators (CollecTRI, top): FOXD3, HNRNPK, PAX6

miRNA regulators (miRDB)

163 targeting CNBP, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-141-3P	99.94	72.79	2421

Literature-anchored findings (GeneRIF, showing 39)

• Six of seven of the Zn(2+) fingers from the CNBP protein can be used as substitutes for the Zn(2+) finger in the NH(2)-terminal position of HIV-1 nucleocapsid, and thus support virus replication (PMID:12857921)
• The proximal myotonic myopathy phenotype is associated with DM2-(CCTG)(n) expansion mutations. (PMID:15261229)
• In twenty-six individuals from a family with DM, the CCTG repeats in ZNF9 were found in normal range. (PMID:15476170)
• results show that a single nucleotide polymorphism located in the first intron of the ZNF9 gene is in linkage disequilibrium with the DM2 mutation (PMID:15652222)
• Results indicate that the (CCTG)n expansion in the ZNF9 intron does not appear to have a direct consequence on the expression of the gene itself. (PMID:16376058)
• the downstream molecular effects of a DM2 mutation are triggered by the accumulation of CCUG repeat tract alone and do not decrease ZNF9 expression at the mRNA or protein level (PMID:16624843)
• We present two first-degree relatives with an athletic clinical phenotype, pathological evidence of subsarcolemmal vacuolation, and molecular genetic confirmation of DM2(the molecular defect of the zinc finger protein 9 gene) (PMID:17068784)
• PCBP2 and ZNF9 stimulate translation of the ornithine decarboxylase internal ribosomal entry site . (PMID:17327219)
• Validated occurrence of an unusual TG 3’ splice site in intron 3. (PMID:17672918)
• These data contribute to the clinical and molecular correlation of ZNF9 gene short expansion in myotonic dystrophy. (PMID:18804219)
• ZNF9 is abundantly expressed in human myofibres, where it is located in the sarcomeric I bands, and no modification of this pattern is observed in myotonic dystrophy type 2 muscles. (PMID:20102514)
• Data identify ZNF9 as a regulator of cap-independent translation and indicate that ZNF9 activity may contribute mechanistically to the myotonic dystrophy type 2 phenotype. (PMID:20174632)
• ZNF9 expression in myotonic dystrophy type 2 patients is altered at multiple levels. (PMID:20971734)
• CCTG repeat expansions in the CNBP gene are responsible for myotonic dystrophy type 2. (PMID:21204798)
• Study concludes that DM2 patients from the Netherlands, including a North-African family, harbor a common haplotype surrounding the ZNF9 gene. (PMID:21224892)
• These data suggest that Gis2 is functionally orthologous to ZNF9 and acts as a cap-independent translation factor. (PMID:21277287)
• Myotonic dystrophy 2(autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.) described in Israeli Jewish European ancestry. (PMID:22332444)
• The co-segregation of Myotonic dystrophy type 2 with a recessive CLCN1 mutation provided the explanation for the unusual clinical findings for juvenile onset of myotonia in a 14-year-old female with Myotonic dystrophy type 2 and her affected mother (PMID:22407275)
• CNBP associates with the poly(A) binding protein and accumulates in stress granules. (PMID:23285195)
• CNBP are novel antigens for SLE patients and the recognition of CNBP might be differentiated dependent on the level of arginine methylation. (PMID:23642268)
• suggested a new possibility of CNBP as a potential anti-cancer target based on CNBP’s biological function in c-myc transcription (PMID:23774591)
• CNBP overexpression caused increase of cell death and suppression of cell metastasis through its induction of G-quadruplex formation in the promoter of hnRNP K resulting in hnRNP K down-regulation (PMID:24594223)
• Arginine methylation of CNBP in the RG motif does not change the subcellular localization but regulates its RNA binding activity. (PMID:24726729)
• High CNBP expression is associated with Medulloblastoma. (PMID:26460945)
• A G-rich motif in the lncRNA Braveheart interacts with Cnbp to specify the cardiovascular lineage. (PMID:27618485)
• The cnbp overexpression rescued the Treacher Collins Syndrome phenotype in a dose-dependent manner by a reactive oxygen species-cytoprotective action that prevented the redox-responsive genes’ upregulation but did not normalize the synthesis of ribosomal RNAs. (PMID:27711076)
• RNA sequence preferences of unconventional RNA-binding proteins, Nudt21 and CNBP, has been described. (PMID:27956239)
• CNBP is supporting translation by resolving stable structures on mRNAs. (PMID:28329689)
• A second point is that DM mutations, although located in noncoding regions, may reduce the expression of mutant alleles, raising questions whether loss-of-function may contribute to the phenotype, or possibly impose a safety limit on knockdown therapies that create or aggravate a DMPK or CNBP deficiency state (PMID:28376341)
• The authors report a previously unknown long noncoding RNA which, together with CNBP, is involved in the fine-tuned regulation of CCND1 mRNA stability, without which CCND1 exhibits, at most, partial expression. (PMID:29199958)
• [CCTG]n repeat expansion, differently from the DM1 mutation, does not influence the methylation status of the CNBP gene and other molecular mechanisms are involved in the pathogenesis of Myotonic Dystrophy type 2.. (PMID:29291944)
• The abnormal expansion of CTG repeats in the 3’-UTR of the DMPK gene elicits Myotonic Dystrophy 1, whereas elongated CCTG repeats in intron 1 of ZNF9 triggers Myotonic Dystrophy 2. (PMID:29651162)
• CNBP controls transcription by unfolding DNA G-quadruplex structures. (PMID:31219592)
• Circ-HuR serves as a tumor suppressor to inhibit CNBP-facilitated HuR expression and gastric cancer progression, indicating a potential therapeutic target for gastric cancer. (PMID:31718709)
• CircPACRGL promoted cell proliferation, migration and invasion as well as inhibited cell apoptosis in colorectal cancer via regulation of the miR-330-3p/CNBP axis. (PMID:36459268)
• Cellular nucleic acid-binding protein restricts SARS-CoV-2 by regulating interferon and disrupting RNA-protein condensates. (PMID:37963251)
• The transcription of the main gene associated with Treacher-Collins syndrome (TCOF1) is regulated by G-quadruplexes and cellular nucleic acid binding protein (CNBP). (PMID:38553547)
• CircPRMT5 promotes progression of osteosarcoma by recruiting CNBP to regulate the translation and stability of CDK6 mRNA. (PMID:38626179)
• STAU1-mediated CNBP mRNA degradation by LINC00665 alters stem cell characteristics in ovarian cancer. (PMID:39080743)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnbpa	ENSDARG00000045776
danio_rerio	cnbpb	ENSDARG00000070922
mus_musculus	Cnbp	ENSMUSG00000030057
rattus_norvegicus	Cnbp	ENSRNOG00000010239
drosophila_melanogaster	CNBP	FBGN0034802
caenorhabditis_elegans		WBGENE00019537

Paralogs (3): ZCCHC9 (ENSG00000131732), ZCCHC7 (ENSG00000147905), ZCCHC13 (ENSG00000187969)

Protein

Protein identifiers

CCHC-type zinc finger nucleic acid binding protein — P62633 (reviewed: P62633)

Alternative names: Cellular nucleic acid-binding protein, Zinc finger protein 9

All UniProt accessions (4): A0A0S2Z4K2, A0A0S2Z4Q3, P62633, D6RAT4

UniProt curated annotations — full annotation on UniProt →

Function. Single-stranded DNA-binding protein that preferentially binds to the sterol regulatory element (SRE) sequence 5’-GTGCGGTG-3’, and thereby mediates transcriptional repression. Has a role as transactivator of the Myc promoter. Binds single-stranded RNA in a sequence-specific manner. Binds G-rich elements in target mRNA coding sequences. Prevents G-quadruplex structure formation in vitro, suggesting a role in supporting translation by resolving stable structures on mRNAs. Binds to RNA. Binds to RNA. Binds to RNA. Binds to RNA. Binds to RNA.

Subunit / interactions. Associates with the 40S ribosomal subunit, the 80S ribosome and with polysomes.

Subcellular location. Nucleus. Cytoplasm. Endoplasmic reticulum Cytoplasm Cytoplasm Cytoplasm Cytoplasm Cytoplasm Cytoplasm.

Tissue specificity. Expressed in the liver, kidney, spleen, testis, lung, muscle and adrenal glands.

Post-translational modifications. Arginine methylation by PRMT1 in the Arg/Gly-rich region impedes RNA binding.

Disease relevance. Dystrophia myotonica 2 (DM2) [MIM:602668] A multisystem disease characterized by the association of proximal muscle weakness with myotonia, cardiac manifestations and cataract. Additional features can include hyperhidrosis, testicular atrophy, insulin resistance and diabetes and central nervous system anomalies in rare cases. The disease is caused by variants affecting the gene represented in this entry. The causative mutation is a CCTG expansion (mean approximately 5000 repeats) located in intron 1 of the CNBP gene.

Induction. Transcriptionally up-regulated by sterol treatment.

Isoforms (8)

UniProt ID	Names	Canonical?
P62633-1	1	yes
P62633-2	2
P62633-3	3
P62633-4	4
P62633-5	5
P62633-6	6
P62633-7	7
P62633-8	8

RefSeq proteins (6): NP_001120664, NP_001120665, NP_001120666, NP_001120667, NP_001120668, NP_003409* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR036875	Znf_CCHC_sf	Homologous_superfamily

Pfam: PF00098

UniProt features (32 total): modified residue 14, zinc finger region 7, splice variant 5, mutagenesis site 2, initiator methionine 1, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62633-F1	71.09	0.00

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 (14): 2, 8, 25, 27, 49, 79, 32, 34, 80, 32, 34, 32, 34, 73

Mutagenesis-validated functional residues (2):

Position	Phenotype
25	significantly reduces methylation; when associated with k-27.
27	significantly reduces methylation; when associated with k-25.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 350 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, E2F_Q4_01, MORF_MBD4, MORF_SMC1L1, TGCGCANK_UNKNOWN, GOBP_STEROL_HOMEOSTASIS, MORF_UBE2I, MORF_RAD21, GTTAAAG_MIR302B, MORF_HDAC2, MORF_PSMC2, GGCNKCCATNK_UNKNOWN, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_LIPID_HOMEOSTASIS

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), positive regulation of cell population proliferation (GO:0008284), cholesterol homeostasis (GO:0042632), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), G-quadruplex DNA formation (GO:0071919), positive regulation of cytoplasmic translation (GO:2000767)

GO Molecular Function (10): RNA binding (GO:0003723), single-stranded RNA binding (GO:0003727), mRNA binding (GO:0003729), zinc ion binding (GO:0008270), translation regulator activity (GO:0045182), G-quadruplex DNA binding (GO:0051880), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
nucleic acid binding	2
RNA binding	2
binding	2
cellular anatomical structure	2
cytoplasm	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
sterol homeostasis	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
DNA metabolic process	1
cytoplasmic translation	1
positive regulation of translation	1
regulation of cytoplasmic translation	1
transition metal ion binding	1
molecular_function	1
regulation of translation	1
DNA binding	1
cation binding	1
intracellular anatomical structure	1
endomembrane system	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

161 interactions, top by confidence:

A	B	Type	Score
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
	CNBP	psi-mi:“MI:0407”(direct interaction)	0.560
CNBP	Prmt1	psi-mi:“MI:0407”(direct interaction)	0.560
CNBP	Prmt1	psi-mi:“MI:0213”(methylation reaction)	0.560
BRD1	KAT7	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
LTK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
MET	NDUFA4	psi-mi:“MI:2364”(proximity)	0.420
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
ZWINT		psi-mi:“MI:0915”(physical association)	0.400
Cnbp	CNBP	psi-mi:“MI:0915”(physical association)	0.400
Mis12	CCN1	psi-mi:“MI:0915”(physical association)	0.400
PRMT1	CNBP	psi-mi:“MI:0915”(physical association)	0.400
CNBP		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (401): CNBP (Affinity Capture-MS), CNBP (Affinity Capture-MS), CNBP (Affinity Capture-MS), CNBP (Affinity Capture-MS), CNBP (Affinity Capture-MS), CNBP (Affinity Capture-MS), CNBP (Affinity Capture-MS), CNBP (Co-fractionation), CNBP (Co-fractionation), CNBP (Co-fractionation), PABPC3 (Co-fractionation), PABPC4 (Co-fractionation), CNBP (Two-hybrid), CNBP (Affinity Capture-MS), CNBP (Affinity Capture-MS)

ESM2 similar proteins: A8WLV5, E0X9N4, O42395, O65639, P09052, P24346, P34689, P36627, P53849, P53996, P62633, P62634, P91599, P92186, Q04832, Q09476, Q0JD07, Q18034, Q3MSQ8, Q3T0Q6, Q4JG17, Q4R5S7, Q54NW4, Q5NU13, Q5R5R5, Q5W5U4, Q5ZA07, Q61496, Q64060, Q67YE6, Q6GWX0, Q6IDS6, Q7F8R0, Q7XPK1, Q84MZ4, Q8T8R1, Q8VZ42, Q8WW36, Q91372, Q94C69

Diamond homologs: O42395, P53996, P62633, P62634, Q3T0Q6, Q5R5R5, Q8RWN5, Q8WW36

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRMT1	down-regulates	CNBP	methylation
CNBP	“down-regulates quantity by repression”	MYC	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 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
Peptide chain elongation	14	17.4×	2e-11
Viral mRNA Translation	13	16.2×	1e-10
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	14	16.2×	2e-11
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	13	16.0×	1e-10
Selenocysteine synthesis	13	15.3×	2e-10
Eukaryotic Translation Termination	13	15.3×	2e-10
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	13	15.0×	2e-10
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	15	14.3×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal large subunit biogenesis	6	21.3×	9e-05
cytoplasmic translation	14	20.7×	5e-12
translation	14	11.5×	1e-08
cell surface receptor protein tyrosine kinase signaling pathway	8	11.1×	1e-04
mRNA transport	5	10.5×	7e-03
rRNA processing	7	7.9×	3e-03
osteoblast differentiation	7	6.8×	6e-03
mRNA splicing, via spliceosome	9	6.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	11
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
17564	NM_003418.5(CNBP):c.-14-833_-14-806CCTG[(75_11000)]	Pathogenic

SpliceAI

943 predictions. Top by Δscore:

Variant	Effect	Δscore
3:129170566:CACAC:C	acceptor_gain	1.0000
3:129170568:CAC:C	acceptor_gain	1.0000
3:129170569:ACCTA:A	acceptor_loss	1.0000
3:129171074:CTTA:C	donor_loss	1.0000
3:129171075:TTAC:T	donor_loss	1.0000
3:129171076:TA:T	donor_loss	1.0000
3:129171078:C:G	donor_loss	1.0000
3:129171089:TC:T	donor_gain	1.0000
3:129171151:T:C	donor_gain	1.0000
3:129171273:GCAGG:G	acceptor_gain	1.0000
3:129171274:CAGG:C	acceptor_gain	1.0000
3:129171274:CAGGC:C	acceptor_gain	1.0000
3:129171276:GG:G	acceptor_gain	1.0000
3:129171278:C:CC	acceptor_gain	1.0000
3:129171278:C:T	acceptor_loss	1.0000
3:129171281:C:CT	acceptor_gain	1.0000
3:129171282:A:T	acceptor_gain	1.0000
3:129171284:CAA:C	acceptor_gain	1.0000
3:129171285:A:T	acceptor_gain	1.0000
3:129171286:A:AC	acceptor_gain	1.0000
3:129171440:ACTT:A	donor_loss	1.0000
3:129171442:TTACC:T	donor_loss	1.0000
3:129171443:TA:T	donor_loss	1.0000
3:129171444:A:AC	donor_gain	1.0000
3:129171444:AC:A	donor_gain	1.0000
3:129171444:ACCAT:A	donor_gain	1.0000
3:129171445:C:CT	donor_gain	1.0000
3:129171445:CC:C	donor_gain	1.0000
3:129171445:CCA:C	donor_gain	1.0000
3:129171445:CCAT:C	donor_gain	1.0000

AlphaMissense

1168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:129170474:G:C	C171W	1.000
3:129170475:C:G	C171S	1.000
3:129170476:A:G	C171R	1.000
3:129170476:A:T	C171S	1.000
3:129170505:C:G	C161S	1.000
3:129170506:A:G	C161R	1.000
3:129170506:A:T	C161S	1.000
3:129170513:A:C	C158W	1.000
3:129170514:C:A	C158F	1.000
3:129170514:C:G	C158S	1.000
3:129170514:C:T	C158Y	1.000
3:129170515:A:G	C158R	1.000
3:129170515:A:T	C158S	1.000
3:129170537:G:C	C150W	1.000
3:129170538:C:G	C150S	1.000
3:129170538:C:T	C150Y	1.000
3:129170539:A:G	C150R	1.000
3:129170539:A:T	C150S	1.000
3:129170547:G:T	A147D	1.000
3:129170552:A:C	H145Q	1.000
3:129170552:A:T	H145Q	1.000
3:129170568:C:A	C140F	1.000
3:129170568:C:G	C140S	1.000
3:129170568:C:T	C140Y	1.000
3:129170569:A:G	C140R	1.000
3:129170569:A:T	C140S	1.000
3:129171084:G:C	C137W	1.000
3:129171085:C:A	C137F	1.000
3:129171085:C:G	C137S	1.000
3:129171085:C:T	C137Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000112184 (3:129177190 A>C,G), RS1000122624 (3:129167417 T>A), RS1000242482 (3:129183533 C>G), RS1000546342 (3:129177455 G>C,T), RS1000887652 (3:129182244 T>A), RS1000920204 (3:129182520 A>C), RS1001095803 (3:129173983 T>C), RS1001219354 (3:129183347 C>A,G), RS1001384790 (3:129168323 TCCA>T), RS1001479076 (3:129179208 C>A,T), RS1001705604 (3:129172947 G>A), RS1001815621 (3:129178806 G>A), RS1001847028 (3:129179858 T>C), RS1001920764 (3:129180064 G>A), RS1001959765 (3:129174350 A>C,T)

Disease associations

OMIM: gene MIM:116955 | disease phenotypes: MIM:602668

GenCC curated gene-disease

Disease	Classification	Inheritance
myotonic dystrophy type 2	Definitive	Autosomal dominant

Mondo (1): myotonic dystrophy type 2 (MONDO:0011266)

Orphanet (1): Proximal myotonic myopathy (Orphanet:606)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000026	Male hypogonadism
HP:0000135	Hypogonadism
HP:0000407	Sensorineural hearing impairment
HP:0000518	Cataract
HP:0000798	Oligozoospermia
HP:0000975	Hyperhidrosis
HP:0001249	Intellectual disability
HP:0001262	Excessive daytime somnolence
HP:0001265	Hyporeflexia
HP:0001348	Brisk reflexes
HP:0001638	Cardiomyopathy
HP:0001649	Tachycardia
HP:0001962	Palpitations
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002292	Frontal balding
HP:0002360	Sleep disturbance
HP:0002486	Myotonia
HP:0002850	Decreased circulating total IgM
HP:0002870	Obstructive sleep apnea
HP:0002926	Abnormality of thyroid physiology
HP:0003077	Hyperlipidemia
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003326	Myalgia
HP:0003327	Axial muscle weakness
HP:0003552	Muscle stiffness
HP:0003554	Type 2 muscle fiber atrophy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005956_82	Waist-to-hip ratio adjusted for BMI	2.000000e-07
GCST005958_5	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-10
GCST005962_16	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067296 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.86	Kd	138	nM	CHEMBL5653589
6.86	ED50	138	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148095: Binding affinity to human CNBP incubated for 45 mins by Kinobead based pull down assay	kd	0.1380	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
arsenite	increases reaction, increases abundance, increases expression, affects binding	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Zinc	affects cotreatment, increases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
geraniol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
afimoxifene	increases expression	1
antimonite	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
GW 7604	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
NSC668394	increases expression	1
Resveratrol	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	increases expression	1
Vorinostat	decreases expression	1
Antimony Potassium Tartrate	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651137	Binding	Binding affinity to human CNBP incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03051243	PHASE3	UNKNOWN	Safety and Efficiency of Linagliptin (Trajenta) in the Setting of Internal Medicine Department
NCT00082108	Not specified	RECRUITING	Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry
NCT02398786	Not specified	RECRUITING	Myotonic Dystrophy Family Registry
NCT02729597	Not specified	COMPLETED	Tracking the Brain in Myotonic Dystrophies: a 5-year Longitudinal Follow-up Study
NCT03211923	Not specified	UNKNOWN	Muscle Relaxation in Myopathies With Positive Muscle Phenomena
NCT03603171	Not specified	COMPLETED	Clinical Outcome Measures in Myotonic Dystrophy Type 2
NCT03867435	Not specified	TERMINATED	Assessing Clinical Endpoints and Biomarkers in Myotonic Dystrophy Type-1 and Type 2 (ASCEND-DM)
NCT04907162	Not specified	COMPLETED	Musculoskeletal Nociceptive Pain in Participants With Neuromuscular Disorders
NCT05854433	Not specified	RECRUITING	Brain Structure and Clinical Endpoints in Myotonic Dystrophy Type 2
NCT06716931	Not specified	RECRUITING	Investigating Exercise in Myotonic Dystrophy Type 2 (DM2)
NCT07072676	Not specified	ENROLLING_BY_INVITATION	The Use of Assistive Gait Devices Can Reduce the Risk of Falls in Patients With Neuromuscular Diseases Following a Training Period.