CNP

protein-coding

2',3'-cyclic nucleotide 3' phosphodiesterase

Gene summary

Predicted to enable 2',3'-cyclic-nucleotide 3'-phosphodiesterase activity. Involved in substantia nigra development. Located in cytoplasm; microtubule; and obsolete extracellular space. Implicated in hypomyelinating leukodystrophy 20; multiple sclerosis; and schizophrenia. Biomarker of alcoholic liver cirrhosis; multiple sclerosis; and restless legs syndrome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_033133.5

Inheritance

ClinVar variants

P:4U:53B:11

Top phenotype

Leukodystrophy, hypomyelinating, 20

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr17:41,966,763-41,977,740

External References & Databases

Ensembl (ENSG00000173786)

Transcript & Mutation Effects

hg38 • Region Span ~11.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

leukodystrophy, hypomyelinating, 20LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0033657

Submitter: Ambry Genetics

leukodystrophy, hypomyelinating, 20LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033657

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Leukodystrophy, hypomyelinating, 20AR

Manifestation: Craniofacial; Dermatologic; Neurologic

Intervention: General

Rationale: 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

Refs: 32128616

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CNP variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 5

Myopia 2, autosomal dominantTotal: 4

CNP-related disorderTotal: 3

Leukodystrophy, hypomyelinating, 20Total: 3

Marfanoid habitus and intellectual disabilityTotal: 1

AchondroplasiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033133.5. 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				4 clinvar	1 clinvar	5
missense	4 clinvar		53 clinvar	6 clinvar		63
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	4	0	53	10	1	68

Highest pathogenic variant AF is 0.0000065684035

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033133.5	RefSeq	NP_149124.3	4	MANE Select
ENST00000393892.8	Ensembl	ENSP00000377470.2	4	MANE Select
NM_001330216.2	RefSeq	NP_001317145.1	3	Standard
ENST00000393888.1	Ensembl	ENSP00000377466.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glial Cell Differentiation
MECP2 and Associated Rett Syndrome

Biological Process

microtubule cytoskeleton organization
chemical synaptic transmission
axonogenesis
aging
adult locomotory behavior

Molecular Function

RNA binding
2',3'-cyclic-nucleotide 3'-phosphodiesterase activity
cyclic nucleotide binding

Cellular Component

extracellular space
nucleus
nucleoplasm
cytoplasm
mitochondrial outer membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393892
Coding exons: 4
Length: 10991
Individuals with no LoFs: 124772
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124777
p: 0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.43	161	274	0.587	0.0000186	2705
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.224

Intolerance Scores

LoFtool: 0.292
RVIS EVS: -0.42
RVIS percentile EVS: 25.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.389

Gene Damage Prediction

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