PRX

periaxin, the group of PDZ domain containing

Basic information

Region (hg38): 19:40393766-40414793

Links

ENSG00000105227 ∙ NCBI:57716 ∙ OMIM:605725 ∙ HGNC:13797 ∙ Uniprot:Q9BXM0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease type 4F (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 3 (Moderate), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 3 (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 4F (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4F (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dejerine-Sottas disease; Charcot-Marie-Tooth disease, type 4F	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	Neurologic	10848494; 11523566; 11157804; 12112076; 16534116; 21079185; 22847150

ClinVar

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

• Charcot-Marie-Tooth_disease_type_4 (1099 variants)
• Inborn_genetic_diseases (422 variants)
• not_provided (320 variants)
• Charcot-Marie-Tooth_disease (205 variants)
• Charcot-Marie-Tooth_disease_type_4F (161 variants)
• not_specified (97 variants)
• PRX-related_disorder (39 variants)
• Dejerine-Sottas_disease (30 variants)
• Charcot-Marie-Tooth_disease,_type_I (8 variants)
• Tip-toe_gait (7 variants)
• Autosomal_recessive_Dejerine-Sottas_syndrome (5 variants)
• Distal_spinal_muscular_atrophy (4 variants)
• Spinocerebellar_ataxia_46 (3 variants)
• Peripheral_neuropathy (2 variants)
• Developmental_cataract (1 variants)
• Progressive_gait_ataxia (1 variants)
• Charcot-Marie-Tooth_disease_type_5 (1 variants)
• Gaucher_disease (1 variants)
• Progressive_peripheral_neuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRX gene is commonly pathogenic or not. These statistics are base on transcript: NM_000181882.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	6	393	5	405
missense	1	2	753	58	6	820
nonsense	16	15	8			39
start loss		1				1
frameshift	33	23	16			72
splice donor/acceptor (+/-2bp)	1	2	1			4
Total	51	44	784	451	11

Highest pathogenic variant AF is 0.000023544

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRX	protein_coding	protein_coding	ENST00000324001	4	19599

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.13e-14	0.589	125629	0	119	125748	0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.131	862	851	1.01	0.0000542	9100
Missense in Polyphen		99	87.276	1.1343		844
Synonymous	-0.0113	376	376	1.00	0.0000250	3363
Loss of Function	1.63	27	37.9	0.713	0.00000253	467

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00169	0.00166
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000712	0.000707
Finnish	0.000426	0.000416
European (Non-Finnish)	0.000296	0.000290
Middle Eastern	0.000712	0.000707
South Asian	0.000297	0.000294
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Scaffolding protein that functions as part of a dystroglycan complex in Schwann cells, and as part of EZR and AHNAK-containing complexes in eye lens fiber cells. Required for the maintenance of the peripheral myelin sheath that is essential for normal transmission of nerve impulses and normal perception of sensory stimuli. Required for normal transport of MBP mRNA from the perinuclear to the paranodal regions. Required for normal remyelination after nerve injury. Required for normal elongation of Schwann cells and normal length of the internodes between the nodes of Ranvier. The demyelinated nodes of Ranvier permit saltatory transmission of nerve impulses; shorter internodes cause slower transmission of nerve impulses. Required for the formation of appositions between the abaxonal surface of the myelin sheath and the Schwann cell plasma membrane; the Schwann cell cytoplasm is restricted to regions between these appositions. Required for the formation of Cajal bands and of Schmidt-Lanterman incisures that correspond to short, cytoplasm-filled regions on myelinated nerves. Recruits DRP2 to the Schwann cell plasma membrane. Required for normal protein composition of the eye lens fiber cell plasma membrane and normal eye lens fiber cell morphology. {ECO:0000250|UniProtKB:O55103}.
• Disease: 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:11133365}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease 4F (CMT4F) [MIM:614895]: A recessive 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. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4F is characterized by distal sensory impairment and distal muscle weakness and atrophy affecting the lower more than the upper limbs. The age at onset is variable and can range from childhood to adult years. When the onset is in infancy, the phenotype is characterized as Dejerine-Sottas syndrome. {ECO:0000269|PubMed:22847150}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.170

Intolerance Scores

• loftool: 0.749
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.17

Haploinsufficiency Scores

• pHI: 0.111
• hipred: N
• hipred_score: 0.337
• ghis: 0.520

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.659

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prx
• 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: axon ensheathment;regulation of RNA splicing
• Cellular component: nucleus;cytoplasm;plasma membrane;cell junction;T-tubule
• Molecular function: molecular_function;protein binding