Peripheral neuropathy: genes and variants

Genes linked to Peripheral neuropathy

• GJB1: Gap junction beta-1 protein

  It forms connexin 32 channels that support metabolic and signaling communication across layers of peripheral myelin produced by Schwann cells. Pathogenic variants cause X-linked Charcot-Marie-Tooth disease type 1, often with transient central nervous system manifestations in some individuals.

  2 disease-causing and 1 uncertain variants in GJB1 are linked to Peripheral neuropathy.

• KIF5A: Kinesin heavy chain isoform 5A

  It drives anterograde transport of organelles and proteins along axonal microtubules and is especially important in long motor neurons. Pathogenic variants can cause hereditary spastic paraplegia, axonal Charcot-Marie-Tooth disease, or amyotrophic lateral sclerosis depending on the affected region and mechanism.

  1 disease-causing and 0 uncertain variants in KIF5A are linked to Peripheral neuropathy.

• 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.

  1 disease-causing and 0 uncertain variants in MFN2 are linked to Peripheral neuropathy.

Weakly linked (only a few uncertain records): KCNJ10, L1CAM and LMNA.

Known disease-causing variants in Peripheral neuropathy

Same protein, different disease

• Charcot-Marie-Tooth Neuropathy X is also caused by GJB1 variants; they fall mostly in different places as the Peripheral neuropathy variants (90 disease-causing).
• Charcot-Marie-Tooth disease is also caused by GJB1 variants; they fall mostly in different places as the Peripheral neuropathy variants (54 disease-causing).
• Hereditary spastic paraplegia is also caused by KIF5A variants; they fall mostly in different places as the Peripheral neuropathy variants (24 disease-causing).
• Charcot-Marie-Tooth disease is also caused by MFN2 variants; they fall mostly in different places as the Peripheral neuropathy variants (86 disease-causing).
• Charcot-Marie-Tooth disease type 2A2 is also caused by MFN2 variants; they fall mostly in different places as the Peripheral neuropathy variants (32 disease-causing).
• Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; is also caused by MFN2 variants; they fall mostly in different places as the Peripheral neuropathy variants (9 disease-causing).
• Neuropathy, hereditary motor and sensory, type 6A is also caused by MFN2 variants; they fall mostly in different places as the Peripheral neuropathy variants (6 disease-causing).
• Hereditary motor and sensory neuropathy with optic atrophy is also caused by MFN2 variants; they fall mostly in different places as the Peripheral neuropathy variants (3 disease-causing).

Diseases related to Peripheral neuropathy

• Charcot-Marie-Tooth disease, also linked to GJB1, KIF5A and MFN2
• Auditory neuropathy, also linked to KIF5A and MFN2
• Hereditary spastic paraplegia, also linked to KIF5A
• Amyotrophic lateral sclerosis, also linked to KIF5A
• Charcot-Marie-Tooth Neuropathy X, also linked to GJB1
• Charcot-Marie-Tooth disease type 2A2, also linked to MFN2
• Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;, also linked to MFN2
• Neuropathy, hereditary motor and sensory, type 6A, also linked to MFN2
• Cerebellar ataxia, also linked to MFN2
• Hereditary motor and sensory neuropathy with optic atrophy, also linked to MFN2
• Myoclonus, intractable, neonatal, also linked to KIF5A

Frequently asked questions

Which genes are linked to Peripheral neuropathy?

In CATVariant, Peripheral neuropathy is linked to 3 analyzed proteins: GJB1 (Gap junction beta-1 protein), KIF5A (Kinesin heavy chain isoform 5A) and MFN2 (Mitofusin-2).

How many genetic variants are linked to Peripheral neuropathy?

8 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 4 are of uncertain significance or have conflicting reports.

Which uncertain variants in Peripheral neuropathy look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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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