PMP22
peripheral myelin protein 22, the group of MicroRNA protein coding host genes
Basic information
Region (hg38): 17:15229773-15272292
Previous symbols: [ "CMT1A" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- Charcot-Marie-Tooth_disease,_type_I (226 variants)
- not_provided (104 variants)
- Charcot-Marie-Tooth_disease (82 variants)
- Inborn_genetic_diseases (38 variants)
- Charcot-Marie-Tooth_disease,_type_IA (34 variants)
- Hereditary_liability_to_pressure_palsies (31 variants)
- Dejerine-Sottas_disease (30 variants)
- Charcot-Marie-Tooth_disease_type_1E (22 variants)
- not_specified (17 variants)
- Roussy-L�vy_syndrome (12 variants)
- Guillain-Barre_syndrome,_familial (10 variants)
- PMP22-related_disorder (9 variants)
- DEJERINE-SOTTAS_SYNDROME,_AUTOSOMAL_DOMINANT (5 variants)
- Tip-toe_gait (4 variants)
- Autosomal_recessive_Dejerine-Sottas_syndrome (1 variants)
- Respiratory_distress (1 variants)
- Peripheral_neuropathy (1 variants)
- Charcot-Marie-Tooth_disease,_type_1a,_autosomal_recessive (1 variants)
- Tongue_fasciculations (1 variants)
- Spasticity (1 variants)
- Charcot-Marie-Tooth_disease_type_2E (1 variants)
- Distal_spinal_muscular_atrophy (1 variants)
- Charcot-Marie-Tooth_disease,_type_1a,_with_focally_folded_myelin_sheaths (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. These statistics are base on transcript: NM_000000304.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 50 | 52 | ||||
| missense | 16 | 28 | 108 | 159 | ||
| nonsense | 10 | 18 | ||||
| start loss | 0 | |||||
| frameshift | 19 | 13 | 41 | |||
| splice donor/acceptor (+/-2bp) | 10 | 23 | ||||
| Total | 55 | 46 | 135 | 57 | 0 |
Highest pathogenic variant AF is 0.0000065717704
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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