Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;: genes and variants

Genes linked to Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;

• MFN2: Mitofusin-2

  It promotes outer-mitochondrial-membrane fusion and coordinates mitochondrial transport, distribution, and contacts with other organelles. Pathogenic variants are a major cause of Charcot-Marie-Tooth disease type 2A and related axonal neuropathies.

  9 ClinVar pathogenic / likely pathogenic and 19 uncertain variants in MFN2 have source records linked to Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;. Association strength is not clinical gene validity.

• ATP1A1: Sodium/potassium-transporting ATPase subunit alpha-1

  It maintains sodium and potassium gradients that underlie membrane potential, secondary transport, and cell-volume control in most tissues. Germline pathogenic variants can cause neurologic or electrolyte disorders, while somatic adrenal variants can drive primary aldosteronism.

  6 ClinVar pathogenic / likely pathogenic and 10 uncertain variants in ATP1A1 have source records linked to Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;. Association strength is not clinical gene validity.

Where Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; variants cluster

• MFN2 Part of a helix bundle domain, formed by helices (positions 30–94): 3 of 9 ClinVar pathogenic / likely pathogenic variants, 3.9× more than its size predicts.
• ATP1A1 Cytoplasmic (positions 343–772): 4 of 6 ClinVar pathogenic / likely pathogenic variants, 1.6× more than its size predicts.

ClinVar pathogenic and likely pathogenic variants linked to Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;

Which prediction tools work for Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;

Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.

• MetaLR: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 92 out of 100
• CATVariant: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Dejerine-Sottas disease also has ClinVar records linked to MFN2 variants; they fall mostly in different places as the Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; variants (101 pathogenic / likely pathogenic).
• Neuropathy, hereditary motor and sensory, type 6A also has ClinVar records linked to MFN2 variants; they fall partly in the same places as the Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; variants (6 pathogenic / likely pathogenic).
• Hypomagnesemia, seizures, and intellectual disability 2 also has ClinVar records linked to ATP1A1 variants; they fall mostly in different places as the Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; variants (6 pathogenic / likely pathogenic).

Diseases related to Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;

• Dejerine-Sottas disease, also linked to MFN2
• Auditory neuropathy, also linked to MFN2
• Hypomagnesemia, seizures, and intellectual disability 2, also linked to ATP1A1
• Neuropathy, hereditary motor and sensory, type 6A, also linked to MFN2
• Peripheral neuropathy, also linked to MFN2
• Hereditary motor and sensory neuropathy with optic atrophy, also linked to MFN2
• Cerebellar ataxia, also linked to MFN2

Frequently asked questions

Which genes have records linked to Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;?

This view contains 2 analyzed proteins: MFN2, ATP1A1. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.

What do the clinical classifications mean?

Linked records include 15 pathogenic or likely pathogenic variants, 18 variants of uncertain significance and 11 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.

Does the evidence score change a VUS classification?

No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.

Can I download the variant evidence?

Download the CSV for all 54 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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