| Variant (protein; cDNA if available) | Variant type | Reported phenotype association | Functional/biochemical notes (residual activity, protein processing, stability, storage material) | Evidence type (human/structural) | Supporting citation ids |
|---|---|---|---|---|---|
| p.Arg329Trp (R329W); cDNA not reported in retrieved evidence | Missense | Kanzaki disease / Schindler type II; angiokeratoma corporis diffusum, intellectual defects, neuroaxonal dystrophy reported in variant-focused review | Structural modeling predicts major conformational change at the interface of domains I and II; patients homozygous for R329W have very low α-NAGA activity (<1% normal); immunoblotting showed no mature α-NAGA band in one R329W patient; patient fibroblasts show lysosomal Tn-antigen accumulation | Human clinical, structural modeling, immunocytochemistry | (pqac-00000027, pqac-00000028, pqac-00000029, pqac-00000006, pqac-00000026) |
| p.Arg329Gln (R329Q); cDNA not reported in retrieved evidence | Missense | Kanzaki disease / Schindler type II; hearing defects, cardiac hypertrophy, peripheral nervous system defects, Ménière-like syndrome/vertigo | Structural modeling predicts conformational change with reduced enzyme stability/function despite location far from active site; homozygous patients had α-NAGA activity below 1% of normal; associated with Tn-antigen lysosomal storage in Kanzaki fibroblasts | Human clinical, structural modeling | (pqac-00000026, pqac-00000027, pqac-00000028, pqac-00000029, pqac-00000006) |
| p.Glu193Ter / p.Glu193* (E193X); exact cDNA not reported in older sources | Nonsense | Mild adult phenotype / Kanzaki disease in Spanish adult siblings; clinically compatible with Schindler type II | Null mutation with complete loss of α-NAGA protein; adult E1.1/E1.2 fibroblast activity around ~0.2 versus control mean 81 (range 40–130); no α-NAGA protein synthesized in metabolic labeling; strong genotype-phenotype paradox because null genotype associated with relatively mild adult phenotype; urinary excretion includes sialylglycopeptides; intracellular storage includes α-GalNAc/Tn-containing material | Human clinical, biochemical, cell biology | (pqac-00000027, pqac-00000029, pqac-00000031, pqac-00000032) |
| c.577G>T (p.Glu193*) | Nonsense | Confirmed in a 68-year-old man with Kanzaki disease / Schindler type II: polyneuropathy, sensorineural hearing loss, chronic lymphedema, angiokeratoma corporis diffusum, bilateral carpal tunnel syndrome | Confirmed by PCR as apparently homozygous; diagnostic context included diminished α-NAGA activity and glycopeptiduria; no disease-modifying therapy established; represents the same protein change as E193X/p.Glu193* | Human clinical case report | (pqac-00000020, pqac-00000021, pqac-00000032, pqac-00000033) |
| p.Glu325Lys (E325K); cDNA not reported in retrieved evidence | Missense | Infantile Schindler disease / type I; severe neuroaxonal phenotype in homozygous brothers, although other reports note phenotypic heterogeneity | Higher residual activity than E193X in reported patients (about 0.6–1.7% of normal); structural change predicted to be smaller and localized near the N-terminal side of the tenth β-strand in domain II; defective phosphorylation/maturation reported in infantile α-NAGA deficiency literature cited by Keulemans | Human clinical, biochemical, structural modeling | (pqac-00000027, pqac-00000029, pqac-00000030) |
| p.Ser160Cys (S160C); cDNA not reported in retrieved evidence | Missense | Schindler disease spectrum; associated in review with psychomotor retardation and convulsions | Identified as one of the disease-causing missense variants analyzed in structural studies; computational work included S160C among variants altering conformational behavior relative to wild-type α-NAGA; not specifically tied to Kanzaki phenotype in retrieved primary evidence | Structural/computational, literature review | (pqac-00000006, pqac-00000019) |


*Table: This table summarizes reported disease-associated NAGA variants relevant to the Schindler/Kanzaki spectrum, linking each variant to phenotype and available functional evidence. It is useful for rapid curation of variant-level molecular and clinical annotations, especially where genotype-phenotype correlation is complex.*