Neuropathy, hereditary sensory, type 2C: genes and variants

Genes linked to Neuropathy, hereditary sensory, type 2C

• KIF1A: Kinesin-like protein KIF1A

  It transports synaptic vesicle precursors and other cargo along axonal microtubules toward nerve terminals. Pathogenic variants cause a broad KIF1A-associated neurological disorder spectrum including hereditary sensory neuropathy, spastic paraplegia, optic atrophy, ataxia, and developmental impairment.

  26 disease-causing and 300 uncertain variants in KIF1A are linked to Neuropathy, hereditary sensory, type 2C.

• ATL1: Atlastin-1

  It promotes homotypic fusion of endoplasmic-reticulum membranes and is required for normal organization of the tubular ER network, especially in long axons. Dominant pathogenic variants are a common cause of hereditary spastic paraplegia type 3A.

  2 disease-causing and 5 uncertain variants in ATL1 are linked to Neuropathy, hereditary sensory, type 2C.

Where Neuropathy, hereditary sensory, type 2C variants cluster

• KIF1A Kinesin motor (positions 5–354): 25 of 26 disease-causing changes, 4.6× more than its size predicts.

Known disease-causing variants in Neuropathy, hereditary sensory, type 2C

Which prediction tools work for Neuropathy, hereditary sensory, type 2C

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• SIFT: 98 out of 100
• CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 86 out of 100
• PolyPhen-2: 70 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Hereditary spastic paraplegia is also caused by KIF1A variants; they fall partly in the same places as the Neuropathy, hereditary sensory, type 2C variants (41 disease-causing).
• Hereditary spastic paraplegia is also caused by ATL1 variants; they fall mostly in different places as the Neuropathy, hereditary sensory, type 2C variants (50 disease-causing).

Diseases related to Neuropathy, hereditary sensory, type 2C

• Hereditary spastic paraplegia, also linked to ATL1 and KIF1A
• Neuropathy, hereditary sensory and autonomic, type 2A, also linked to KIF1A
• Autosomal recessive spastic paraplegia type 78, also linked to KIF1A

Frequently asked questions

Which genes are linked to Neuropathy, hereditary sensory, type 2C?

In CATVariant, Neuropathy, hereditary sensory, type 2C is linked to 2 analyzed proteins: KIF1A (Kinesin-like protein KIF1A) and ATL1 (Atlastin-1).

How many genetic variants are linked to Neuropathy, hereditary sensory, type 2C?

355 variants: 28 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 305 are of uncertain significance or have conflicting reports.

Which uncertain variants in Neuropathy, hereditary sensory, type 2C look disease-causing?

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

Which variant effect predictor works best for Neuropathy, hereditary sensory, type 2C?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.98, based on 20 disease-causing and 16 harmless variants).

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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