PMP22

peripheral myelin protein 22, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 17:15229772-15272292

Previous symbols: [ "CMT1A" ]

Links

ENSG00000109099 ∙ NCBI:5376 ∙ OMIM:601097 ∙ HGNC:9118 ∙ Uniprot:Q01453 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease type 1E (Moderate), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 1A (Definitive), mode of inheritance: AD
• hereditary neuropathy with liability to pressure palsies (Definitive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 1E (Moderate), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 1A (Definitive), mode of inheritance: AD
• hereditary neuropathy with liability to pressure palsies (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 3 (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 1E (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 1A (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 1A (Strong), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 1E (Strong), mode of inheritance: AD
• hereditary neuropathy with liability to pressure palsies (Strong), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 1A (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Roussy-Levy syndrome; Charcot-Marie-Tooth syndrome, type 1A; Charcot-Marie-Tooth syndrome with deafness (type 1E); Neuropathy, hereditary, with liability to pressurve palsies; Dejerine-Sottas disease; Neuropathy, inflammatory demyelinating	AD/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	Audiologic/Otolaryngologic; Neurologic	13184660; 7139106; 2290479; 1349106; 1303281; 8422677; 7834893; 7903071; 8012388; 8210227; 7501152; 7666403; 8644705; 8981968; 9208274; 9179161; 9391880; 9543325; 9703447; 10489052; 10330345; 10211478; 11376203; 11835375; 12439896; 12499508; 12427913; 12084875; 12578939; 15205993; 17620487; 18698610; 19705173; 19888301; 20301566; 20301384; 22006697; 22190321; 22382358
CMT, 1A can be due to a common 17p11.2 duplication; The variant type (eg, deletions vs. duplications) influences the phenotype; Compound heterozygous variants have been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PMP22 gene.

• Charcot-Marie-Tooth disease, type I (221 variants)
• not provided (107 variants)
• Charcot-Marie-Tooth disease (51 variants)
• Hereditary liability to pressure palsies (47 variants)
• Inborn genetic diseases (32 variants)
• not specified (22 variants)
• Charcot-Marie-Tooth disease, type IA (15 variants)
• Dejerine-Sottas disease (10 variants)
• 6 conditions (7 variants)
• Charcot-Marie-Tooth disease type 1E (5 variants)
• Dejerine-Sottas syndrome, autosomal dominant (4 variants)
• Roussy-Lévy syndrome (3 variants)
• Tip-toe gait (2 variants)
• Charcot-Marie-Tooth disease type 2E (1 variants)
• Charcot-Marie-Tooth disease type 1E;Dejerine-Sottas disease (1 variants)
• Spasticity;Respiratory distress;Tongue fasciculations (1 variants)
• Autosomal recessive Dejerine-Sottas syndrome (1 variants)
• PMP22-Related Disorders (1 variants)
• Distal spinal muscular atrophy (1 variants)
• Charcot-Marie-Tooth disease, type IA;Hereditary liability to pressure palsies;Charcot-Marie-Tooth disease type 1E (1 variants)
• Charcot-Marie-Tooth disease, type 1a, autosomal recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMP22 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				19		19
missense	11	14	78	26	1	130
nonsense	11	4		3		18
start loss	1					1
frameshift	13	5		1		19
inframe indel			5			5
splice donor/acceptor (+/-2bp)	6	3				9
splice region		1	3	8		12
non coding			14	34	15	63
Total	42	26	97	83	16

Highest pathogenic variant AF is 0.00000657

Variants in PMP22

This is a list of pathogenic ClinVar variants found in the PMP22 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-15229797-A-G		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Likely benign (Jun 14, 2016)
17-15229806-C-A		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Likely benign (Jun 14, 2016)
17-15229868-G-C		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Uncertain significance (Jan 12, 2018)
17-15229932-G-A		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Uncertain significance (Jan 12, 2018)
17-15229956-G-C		Hereditary liability to pressure palsies • Charcot-Marie-Tooth disease, type I	Uncertain significance (Jan 12, 2018)
17-15230005-C-T		Hereditary liability to pressure palsies • Charcot-Marie-Tooth disease, type I	Benign (Jan 13, 2018)
17-15230006-G-A		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Uncertain significance (Jan 13, 2018)
17-15230010-G-T		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Uncertain significance (Jan 13, 2018)
17-15230023-G-A		Hereditary liability to pressure palsies • Charcot-Marie-Tooth disease, type I	Uncertain significance (Jan 13, 2018)
17-15230027-G-A		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Benign (Jan 13, 2018)
17-15230089-C-T		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Likely benign (Jun 14, 2016)
17-15230099-A-G		Hereditary liability to pressure palsies • Charcot-Marie-Tooth disease, type I	Uncertain significance (Jan 12, 2018)
17-15230321-C-A		Hereditary liability to pressure palsies • Charcot-Marie-Tooth disease, type I	Uncertain significance (Jan 12, 2018)
17-15230340-A-G		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Likely benign (Jun 14, 2016)
17-15230373-G-A		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Uncertain significance (Jan 12, 2018)
17-15230375-G-A		Hereditary liability to pressure palsies • Charcot-Marie-Tooth disease, type I	Uncertain significance (Jan 13, 2018)
17-15230388-CAG-C		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Likely benign (Jun 14, 2016)
17-15230541-G-A		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Benign (Jan 13, 2018)
17-15230674-G-A		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Uncertain significance (Jan 13, 2018)
17-15230689-C-T		Hereditary liability to pressure palsies • Charcot-Marie-Tooth disease, type I	Benign/Likely benign (Jun 14, 2018)
17-15230712-G-T		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Conflicting classifications of pathogenicity (Jan 24, 2020)
17-15230717-A-C		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Benign (Jan 11, 2020)
17-15230719-G-C			Benign (Dec 11, 2019)
17-15230743-C-T		Hereditary liability to pressure palsies • Charcot-Marie-Tooth disease, type I	Uncertain significance (Jan 15, 2018)
17-15230744-G-A		Charcot-Marie-Tooth disease, type I • Hereditary liability to pressure palsies	Benign/Likely benign (Jan 23, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PMP22	protein_coding	protein_coding	ENST00000395938	4	35549

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.910	0.0898	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.417	79	90.1	0.876	0.00000538	1023
Missense in Polyphen		30	40.101	0.74811		455
Synonymous	-0.282	44	41.7	1.06	0.00000286	335
Loss of Function	2.58	0	7.74	0.00	3.46e-7	80

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: Might be involved in growth regulation, and in myelinization in the peripheral nervous system.
• Disease: DISEASE: Charcot-Marie-Tooth disease 1A (CMT1A) [MIM:118220]: A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. {ECO:0000269|PubMed:10489052, ECO:0000269|PubMed:10737979, ECO:0000269|PubMed:11140841, ECO:0000269|PubMed:11835375, ECO:0000269|PubMed:12402337, ECO:0000269|PubMed:12497641, ECO:0000269|PubMed:1303281, ECO:0000269|PubMed:15205993, ECO:0000269|PubMed:8252046, ECO:0000269|PubMed:8510709, ECO:0000269|PubMed:8615087, ECO:0000269|PubMed:8655153, ECO:0000269|PubMed:8777804, ECO:0000269|PubMed:9040744}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dejerine-Sottas syndrome (DSS) [MIM:145900]: A severe degenerating neuropathy of the demyelinating Charcot-Marie-Tooth disease category, with onset by age 2 years. Characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome. {ECO:0000269|PubMed:10211478, ECO:0000269|PubMed:10663978, ECO:0000269|PubMed:11438991, ECO:0000269|PubMed:12090401, ECO:0000269|PubMed:7675244, ECO:0000269|PubMed:7728152, ECO:0000269|PubMed:8252046, ECO:0000269|PubMed:8275092, ECO:0000269|PubMed:8995589, ECO:0000269|PubMed:9004143, ECO:0000269|PubMed:9055797, ECO:0000269|PubMed:9187667, ECO:0000269|PubMed:9452053, ECO:0000269|PubMed:9544841, ECO:0000269|PubMed:9585367, ECO:0000269|PubMed:9633821}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hereditary neuropathy with liability to pressure palsies (HNPP) [MIM:162500]: A neurologic disorder characterized by transient episodes of decreased perception or peripheral nerve palsies after slight traction, compression or minor traumas. {ECO:0000269|PubMed:12796555, ECO:0000269|PubMed:15205993, ECO:0000269|PubMed:9748013}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease 1E (CMT1E) [MIM:118300]: An autosomal dominant form of Charcot-Marie-Tooth disease characterized by the association of sensorineural hearing loss with peripheral demyelinating neuropathy. {ECO:0000269|PubMed:10330345, ECO:0000269|PubMed:11835375, ECO:0000269|PubMed:12578939, ECO:0000269|PubMed:15099592}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Inflammatory demyelinating polyneuropathy (IDP) [MIM:139393]: Putative autoimmune disorder presenting in an acute (AIDP) or chronic form (CIDP). The acute form is also known as Guillain-Barre syndrome. {ECO:0000269|PubMed:12439896}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Neural Crest Differentiation;a6b1 and a6b4 Integrin signaling (Consensus)

Recessive Scores

• pRec: 0.417

Intolerance Scores

• loftool: 0.0761
• rvis_EVS: 0.28
• rvis_percentile_EVS: 71.08

Haploinsufficiency Scores

• pHI: 0.885
• hipred: Y
• hipred_score: 0.638
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.741

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pmp22
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism 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); reproductive system 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); hearing/vestibular/ear phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: chemical synaptic transmission;peripheral nervous system development;cell death;negative regulation of cell population proliferation;negative regulation of neuron projection development;bleb assembly;myelin assembly;myelination
• Cellular component: plasma membrane;bicellular tight junction;integral component of membrane;compact myelin
• Molecular function: protein binding