CNBP

CCHC-type zinc finger nucleic acid binding protein, the group of Zinc fingers CCHC-type

Basic information

Region (hg38): 3:129167826-129183922

Previous symbols: [ "DM2", "ZNF9" ]

Links

ENSG00000169714 ∙ NCBI:7555 ∙ OMIM:116955 ∙ HGNC:13164 ∙ Uniprot:P62633 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myotonic dystrophy type 2 (Supportive), mode of inheritance: AD
• myotonic dystrophy type 2 (Strong), mode of inheritance: AD
• myotonic dystrophy type 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myotonic dystrophy 2	AD	Cardiovascular	The condition can include cardiovascular manifestions, including arrhythmias (sudden cardiac death has been reported), left ventricular dysfunction, and congestive heart failure, and surveillance (eg, with EKG and echocardiogram), as well as early interventions and medical management, may decrease morbidity and mortality	Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Obstetric; Ophthalmologic	10078095; 11486088; 12970845; 12601109; 14505273; 15503094; 15503094; 15623712; 16258778; 16684600; 18057971; 19020295; 19481939; 20301639; 20627570; 22587749; 23561036
Individuals with bi-allelic variants and severe cardiac manifestations have been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNBP gene.

• Inborn genetic diseases (4 variants)
• not provided (2 variants)
• Myotonic dystrophy type 2 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNBP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	0	1

Variants in CNBP

This is a list of pathogenic ClinVar variants found in the CNBP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-129170530-T-C		Inborn genetic diseases	Uncertain significance (Jul 17, 2023)
3-129171157-T-C		Inborn genetic diseases	Uncertain significance (Sep 21, 2021)
3-129171185-G-C		Inborn genetic diseases	Uncertain significance (Mar 17, 2023)
3-129171196-T-C		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
3-129171264-G-A		CNBP-related disorder	Likely benign (May 30, 2019)
3-129171507-G-A		Myotonic dystrophy type 2 • CNBP-related disorder	Benign (Jul 22, 2021)
3-129171507-G-T		Myotonic dystrophy type 2	Uncertain significance (Jul 21, 2019)
3-129171697-T-C			Uncertain significance (Nov 03, 2021)
3-129171743-C-G		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
3-129172600-GCAGGCAGA-G		CNBP-related disorder	Likely benign (Feb 16, 2023)
3-129172608-ACAGGCAGACAGGCAGC-A		CNBP-related disorder	Likely benign (Sep 13, 2021)
3-129172608-ACAGGCAGACAGGCAGCCAGG-A		CNBP-related disorder	Likely benign (Jun 15, 2021)
3-129172695-GAC-G		CNBP-related disorder	Likely benign (Mar 23, 2023)
3-129172734-T-A		CNBP-related disorder	Likely benign (Oct 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNBP	protein_coding	protein_coding	ENST00000441626	4	14439

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.960	0.0400	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.38	42	113	0.370	0.00000680	1179
Missense in Polyphen		5	33.821	0.14784		371
Synonymous	0.600	32	36.6	0.874	0.00000208	325
Loss of Function	2.94	0	10.0	0.00	6.06e-7	113

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Single-stranded DNA-binding protein, with specificity to the sterol regulatory element (SRE). Involved in sterol-mediated repression.
• Disease: DISEASE: 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. Note=The disease is caused by mutations 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.

Recessive Scores

• pRec: 0.440

Intolerance Scores

• loftool: 0.0821
• rvis_EVS: 0.3
• rvis_percentile_EVS: 71.81

Haploinsufficiency Scores

• pHI: 0.870
• hipred: Y
• hipred_score: 0.675

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cnbp
• Phenotype: craniofacial phenotype; cellular phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; skeleton phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: cnbpa
• Affected structure: chondrocyte
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;cholesterol biosynthetic process;positive regulation of cell population proliferation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;endoplasmic reticulum;cytosol
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;single-stranded DNA binding;DNA-binding transcription factor activity;RNA binding;single-stranded RNA binding;protein binding;zinc ion binding