CNBP

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2016]

Previous symbols:

DM2
ZNF9

MANE transcript

NM_003418.5

Inheritance

ClinVar variants

U:18B:1

Top phenotype

Myotonic dystrophy 2

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr3:129,167,827-129,183,922

External References & Databases

Ensembl (ENSG00000169714)

Transcript & Mutation Effects

hg38 • Region Span ~16.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

myotonic dystrophy type 2DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011266

Submitter: G2P

myotonic dystrophy type 2SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011266

Submitter: Orphanet

myotonic dystrophy type 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011266

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Myotonic dystrophy 2AD

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Obstetric; Ophthalmologic

Intervention: Cardiovascular

Rationale: 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

Comments: Individuals with bi-allelic variants and severe cardiac manifestations have been described

Refs: 10078095; 11486088; 12970845; 12601109; 14505273; 15503094; 15503094; 15623712; 16258778; 16684600; 18057971; 19020295; 19481939; 20301639; 20627570; 22587749; 23561036

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CNBP variants in ClinVar

4 Conditions Cataloged

Inborn genetic diseasesTotal: 9

CNBP-related disorderTotal: 5

not providedTotal: 2

Myotonic dystrophy type 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003418.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			12 clinvar			12
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	18	1	0	19

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 118 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003418.5	RefSeq	NP_003409.1	4	MANE Select
ENST00000422453.7	Ensembl	ENSP00000410619.3	4	MANE Select
NM_001127192.2	RefSeq	NP_001120664.1	4	Standard
NM_001127193.2	RefSeq	NP_001120665.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cnbpa	Danio rerio	Structure: chondrocyte Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

cnbpa

Danio rerio

Structure: chondrocyte

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

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

Cellular Component

nucleus
endoplasmic reticulum
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000441626
Coding exons: 4
Length: 14439
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.38	42	113	0.370	0.00000680	1179
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.985

Gene Damage Prediction

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