PLP1

proteolipid protein 1

Basic information

Region (hg38): X:103773718-103792619

Previous symbols: [ "SPG2", "PLP" ]

Links

ENSG00000123560 ∙ NCBI:5354 ∙ OMIM:300401 ∙ HGNC:9086 ∙ Uniprot:P60201 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Pelizeaus-Merzbacher spectrum disorder (Definitive), mode of inheritance: XLR
• hereditary spastic paraplegia 2 (Definitive), mode of inheritance: XLR
• Pelizeaus-Merzbacher spectrum disorder (Strong), mode of inheritance: XL
• Pelizeaus-Merzbacher spectrum disorder (Definitive), mode of inheritance: XL
• hereditary spastic paraplegia 2 (Moderate), mode of inheritance: XL
• hereditary spastic paraplegia 2 (Supportive), mode of inheritance: XL
• Pelizaeus-Merzbacher disease, connatal form (Supportive), mode of inheritance: XL
• Pelizaeus-Merzbacher disease, classic form (Supportive), mode of inheritance: XL
• Pelizaeus-Merzbacher disease, transitional form (Supportive), mode of inheritance: XL
• Pelizaeus-Merzbacher disease in female carriers (Supportive), mode of inheritance: XL
• null syndrome (Supportive), mode of inheritance: XL
• Pelizeaus-Merzbacher spectrum disorder (Definitive), mode of inheritance: XL
• hereditary spastic paraplegia 2 (Definitive), mode of inheritance: XL
• Pelizeaus-Merzbacher spectrum disorder (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 2, X-linked; Pelizaeus-Merzbacher disease	XL	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	Musculoskeletal; Neurologic; Ophthalmologic	2479017; 2773936; 7539211; 8659540; 8696336; 10210128; 10417279; 11093273; 11761472; 15627202; 16130097; 16157902; 16374829; 16778599; 17438221; 17568416; 18190592; 19396823; 20513814; 20660364; 21623770; 22422208; 27882623; 29478609; 29486744

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLP1 gene.

• Hereditary spastic paraplegia 2 (32 variants)
• Pelizaeus-Merzbacher disease (14 variants)
• not provided (14 variants)
• Inborn genetic diseases (3 variants)
• Pelizaeus-Merzbacher disease, mild (1 variants)
• Pelizaeus-Merzbacher disease, atypical (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLP1 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	1		2	52	6	61
missense	7	21	90	1	3	122
nonsense	14	3				17
start loss	4					4
frameshift	12	2	1			15
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	9	3	1			13
splice region	1	1	5	4		11
non coding	2		2	32	16	52
Total	49	30	98	85	25

Variants in PLP1

This is a list of pathogenic ClinVar variants found in the PLP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-103776653-C-A			Uncertain significance (Jun 18, 2021)
X-103776772-A-AG			Benign (Apr 21, 2019)
X-103776774-GGAGGAGGAGA-G			Likely benign (Oct 13, 2020)
X-103776802-C-T			Likely benign (Jan 01, 2023)
X-103776965-C-T		Hereditary spastic paraplegia 2 • Pelizaeus-Merzbacher disease • Pelizaeus-Merzbacher disease, mild • Pelizaeus-Merzbacher disease;Hereditary spastic paraplegia 2	Benign/Likely benign (Mar 23, 2023)
X-103776996-A-G		Pelizaeus-Merzbacher disease • Hereditary spastic paraplegia 2	Pathogenic (Aug 04, 2021)
X-103776997-T-A		Pelizaeus-Merzbacher disease	Pathogenic (Mar 31, 2021)
X-103776997-T-C		Hereditary spastic paraplegia 2 • Inborn genetic diseases	Pathogenic (Dec 30, 2020)
X-103776997-T-G		Inborn genetic diseases • Hereditary spastic paraplegia 2 • Pelizaeus-Merzbacher disease	Pathogenic (Nov 01, 2023)
X-103776997-TG-T		Hereditary spastic paraplegia 2 • Pelizaeus-Merzbacher disease	Pathogenic (Nov 22, 2021)
X-103776998-G-A		Pelizaeus-Merzbacher disease, mild • Hereditary spastic paraplegia 2	Pathogenic (Nov 27, 2023)
X-103776999-G-C			Uncertain significance (Jan 17, 2023)
X-103777000-G-A		Hereditary spastic paraplegia 2	Pathogenic (Nov 27, 2023)
X-103777003-A-C		Inborn genetic diseases • Hereditary spastic paraplegia 2	Uncertain significance (Nov 08, 2022)
X-103777004-G-A		Pelizaeus-Merzbacher disease	Uncertain significance (Sep 09, 2022)
X-103777015-T-C		Hereditary spastic paraplegia 2	Likely benign (Apr 25, 2023)
X-103777073-G-T		PLP1-related disorder	Likely benign (Jul 07, 2022)
X-103777080-G-A		PLP1-related disorder	Uncertain significance (Jul 23, 2024)
X-103781981-AG-A		not specified	Benign (-)
X-103783933-G-GTATATATACATATATTTA		not specified	Benign (-)
X-103785471-T-C			Benign (Jun 14, 2018)
X-103785565-C-T		Hereditary spastic paraplegia 2	Likely benign (Nov 21, 2023)
X-103785567-C-G		Hereditary spastic paraplegia 2	Benign (Jan 07, 2024)
X-103785567-C-CT		Hereditary spastic paraplegia 2	Likely benign (Nov 21, 2023)
X-103785568-T-C		Hereditary spastic paraplegia 2	Benign (Nov 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLP1	protein_coding	protein_coding	ENST00000418604	7	18902

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.928	0.0712	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.04	45	103	0.436	0.00000755	1791
Missense in Polyphen		17	47.887	0.355		856
Synonymous	-0.137	44	42.9	1.03	0.00000349	570
Loss of Function	2.69	0	8.42	0.00	5.34e-7	161

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: This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin.
• Disease: DISEASE: Leukodystrophy, hypomyelinating, 1 (HLD1) [MIM:312080]: A X-linked recessive disorder of the central nervous system in which myelin is not formed properly. Clinically characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay. {ECO:0000269|PubMed:10417279, ECO:0000269|PubMed:10425042, ECO:0000269|PubMed:11093273, ECO:0000269|PubMed:11786921, ECO:0000269|PubMed:1376966, ECO:0000269|PubMed:1384324, ECO:0000269|PubMed:15712223, ECO:0000269|PubMed:1707231, ECO:0000269|PubMed:1708672, ECO:0000269|PubMed:1715570, ECO:0000269|PubMed:2479017, ECO:0000269|PubMed:2480601, ECO:0000269|PubMed:2773936, ECO:0000269|PubMed:7531827, ECO:0000269|PubMed:7539213, ECO:0000269|PubMed:7541731, ECO:0000269|PubMed:7573159, ECO:0000269|PubMed:7679906, ECO:0000269|PubMed:7683951, ECO:0000269|PubMed:7684886, ECO:0000269|PubMed:8037216, ECO:0000269|PubMed:8909455, ECO:0000269|PubMed:9008538, ECO:0000269|PubMed:9143933, ECO:0000269|PubMed:9482656, ECO:0000269|PubMed:9633722, ECO:0000269|PubMed:9747038, ECO:0000269|PubMed:9788732, ECO:0000269|PubMed:9894878, ECO:0000269|PubMed:9934976}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 2, X-linked (SPG2) [MIM:312920]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG2 is characterized by spastic gait and hyperreflexia. In some patients, complicating features include nystagmus, dysarthria, sensory disturbance, mental retardation, optic atrophy. {ECO:0000269|PubMed:10319897, ECO:0000269|PubMed:11093273, ECO:0000269|PubMed:15450775, ECO:0000269|PubMed:17438221, ECO:0000269|PubMed:24103481, ECO:0000269|PubMed:7522741, ECO:0000269|PubMed:8012387, ECO:0000269|PubMed:8780101, ECO:0000269|PubMed:8956049, ECO:0000269|PubMed:9489796}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glial Cell Differentiation;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways (Consensus)

Recessive Scores

• pRec: 0.368

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.954
• hipred: Y
• hipred_score: 0.768
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plp1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton 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; vision/eye phenotype; hematopoietic 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); reproductive system phenotype

Gene ontology

• Biological process: inflammatory response;integrin-mediated signaling pathway;chemical synaptic transmission;axon ensheathment;glial cell differentiation;positive regulation of gene expression;astrocyte development;substantia nigra development;central nervous system myelination;neuron projection development;myelination;long-chain fatty acid biosynthetic process;axon development
• Cellular component: plasma membrane;integral component of membrane;myelin sheath
• Molecular function: structural molecule activity;protein binding;structural constituent of myelin sheath