CNP

2',3'-cyclic nucleotide 3' phosphodiesterase

Basic information

Region (hg38): 17:41966763-41977740

Links

ENSG00000173786 ∙ NCBI:1267 ∙ OMIM:123830 ∙ HGNC:2158 ∙ Uniprot:P09543 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukodystrophy, hypomyelinating, 20 (Limited), mode of inheritance: AR
• leukodystrophy, hypomyelinating, 20 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 20	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dermatologic; Neurologic	32128616

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNP 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				3	1	4
missense			20	2		22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2		1	3
Total	0	0	22	5	2

Variants in CNP

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

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

Position	Type	Phenotype	Significance	ClinVar
17-41966808-C-T		Myopia 2, autosomal dominant	Pathogenic (Oct 14, 2019)
17-41966818-C-T		Myopia 2, autosomal dominant	Pathogenic (Oct 14, 2019)
17-41968089-A-G		not specified	Uncertain significance (Feb 27, 2024)
17-41968123-A-C		Myopia 2, autosomal dominant	Pathogenic (Oct 14, 2019)
17-41968123-A-G		Myopia 2, autosomal dominant	Pathogenic (Oct 14, 2019)
17-41968309-C-T		Leukodystrophy, hypomyelinating, 20	Pathogenic (Nov 10, 2020)
17-41968338-G-A		not specified	Uncertain significance (Oct 26, 2022)
17-41968342-G-A		not specified	Uncertain significance (Dec 15, 2021)
17-41968442-C-T			Likely benign (Aug 01, 2022)
17-41968457-G-A			Likely benign (Aug 01, 2023)
17-41968625-G-A		CNP-related disorder	Likely benign (Feb 03, 2023)
17-41968712-C-A		not specified	Uncertain significance (Mar 20, 2024)
17-41971906-G-A		not specified	Uncertain significance (Jun 16, 2024)
17-41971920-G-C		CNP-related disorder	Likely benign (Dec 01, 2022)
17-41972016-G-T		not specified	Likely benign (Sep 14, 2022)
17-41973492-C-T			Likely benign (Jul 01, 2024)
17-41973500-C-T		Leukodystrophy, hypomyelinating, 20	Uncertain significance (-)
17-41973506-C-T		not specified	Uncertain significance (Mar 24, 2023)
17-41973523-C-T		not specified	Uncertain significance (Apr 25, 2023)
17-41973565-A-C		not specified	Uncertain significance (Jun 17, 2024)
17-41973566-G-A		not specified	Uncertain significance (Jun 18, 2024)
17-41973568-G-A		not specified	Uncertain significance (Dec 13, 2022)
17-41973568-G-C		not specified	Uncertain significance (Aug 22, 2023)
17-41973576-ACTG-CCTA		Leukodystrophy, hypomyelinating, 20	Uncertain significance (-)
17-41973588-G-T		not specified	Uncertain significance (Aug 28, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNP	protein_coding	protein_coding	ENST00000393892	4	10991

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.984	0.0159	124772	0	5	124777	0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.43	161	274	0.587	0.0000186	2705
Missense in Polyphen		38	86.704	0.43827		820
Synonymous	0.900	112	125	0.897	0.00000866	877
Loss of Function	3.59	1	17.0	0.0589	0.00000103	188

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000293	0.0000293
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000270	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin. {ECO:0000250}.
• Pathway: Glial Cell Differentiation;MECP2 and Associated Rett Syndrome (Consensus)

Recessive Scores

• pRec: 0.224

Intolerance Scores

• loftool: 0.292
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.193
• hipred: Y
• hipred_score: 0.673
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.389

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cnp
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; skeleton phenotype; immune system phenotype; vision/eye 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); digestive/alimentary phenotype; reproductive system 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); hematopoietic system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: microtubule cytoskeleton organization;chemical synaptic transmission;axonogenesis;aging;adult locomotory behavior;cyclic nucleotide catabolic process;response to toxic substance;substantia nigra development;forebrain development;response to lipopolysaccharide;regulation of mitochondrial membrane permeability;oligodendrocyte differentiation
• Cellular component: extracellular space;nucleus;nucleoplasm;cytoplasm;mitochondrial outer membrane;mitochondrial inner membrane;cytosol;plasma membrane;microvillus;membrane;pseudopodium;myelin sheath abaxonal region;myelin sheath adaxonal region;melanosome;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: RNA binding;2',3'-cyclic-nucleotide 3'-phosphodiesterase activity;cyclic nucleotide binding