PMP2

peripheral myelin protein 2, the group of Fatty acid binding protein family

Basic information

Region (hg38): 8:81440326-81447439

Links

ENSG00000147588

∙ NCBI:5375 ∙ OMIM:170715 ∙ HGNC:9117 ∙ Uniprot:P02689 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Charcot-Marie-Tooth disease, demyelinating, type 1G (Moderate), mode of inheritance: AD
Charcot-Marie-Tooth disease, demyelinating, type 1G (Strong), mode of inheritance: AD
Charcot-Marie-Tooth disease, demyelinating, type 1G (Supportive), mode of inheritance: AD
Charcot-Marie-Tooth disease (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, demyelinating, type 1G	AD	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	Neurologic	26257172; 26828946; 27009151; 30249361

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PMP2 gene.

not_provided (105 variants)
Inborn_genetic_diseases (14 variants)
Charcot-Marie-Tooth_disease,_demyelinating,_type_1G (8 variants)
PMP2-related_disorder (5 variants)
Peripheral_neuropathy (2 variants)
not_specified (1 variants)
Charcot-Marie-Tooth_disease_type_1E (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002677.5. 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			3 clinvar	14 clinvar		17
missense	1 clinvar	4 clinvar	51 clinvar	4 clinvar	4 clinvar	64
nonsense			2 clinvar			2
start loss			1			1
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	1	4	59	18	4

Highest pathogenic variant AF is 6.84214e-7

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PMP2	protein_coding	protein_coding	ENST00000256103	4	7198

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00847	0.810	125722	0	8	125730	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0996	67	69.3	0.966	0.00000334	863
Missense in Polyphen		17	17.503	0.97127		247
Synonymous	0.554	22	25.6	0.861	0.00000135	241
Loss of Function	1.05	4	6.99	0.572	3.93e-7	82

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000359	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: May play a role in lipid transport protein in Schwann cells. May bind cholesterol. {ECO:0000269|PubMed:20421974}.;
Pathway: Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway (Consensus)

Recessive Scores

pRec: 0.364

Intolerance Scores

loftool: 0.585
rvis_EVS: 0.55
rvis_percentile_EVS: 81.22

Haploinsufficiency Scores

pHI: 0.146
hipred: N
hipred_score: 0.310
ghis: 0.409

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.262

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pmp2
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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Gene ontology

Biological process: membrane organization
Cellular component: cytoplasm;myelin sheath;extracellular exosome
Molecular function: fatty acid binding;protein binding;cholesterol binding