Table 1.
Number of variants in J proteins, otherwise referred to as Hsp40s, previously associated with neurological phenotypes and/or phenotypes presenting with neurological features.
| Gene | Disease | ClinVar Pathogenic | ClinVar Likely Pathogenic | ||
|---|---|---|---|---|---|
| Missense | LoF | Missense | LoF | ||
| DNAJA3 | Developmental delay and polyneuropathy | NA | NA | NA | NA |
| DNAJB2 | Charcot–Marie–Tooth disease; distal spinal muscular atrophy | NA | 7 | 2 | 4 |
| DNAJB5 | Peripheral neuropathy; skeletal myopathy; peripheral neuropathy | NA | NA | 1 | NA |
| DNAJB6 | Limb–girdle muscular dystrophy, type 1E; frontotemporal dementia | 8 | 1 | 4 | NA |
| DNAJC3 | Combined cerebellar and peripheral ataxia with hearing loss and diabetes mellitus | NA | 3 | NA | 1 |
| DNAJC5 | Neuronal ceroid lipofuscinosis | 1 | 2 | NA | NA |
| DNAJC6 | Juvenile-onset Parkinson’s disease 19a | 2 | 9 | NA | NA |
| DNAJC7 | Amyotrophic lateral sclerosis | NA | NA | NA | NA |
| DNAJC12 | Mild hyperphenylalaninemia, non-bh4-deficient; early-onset parkinsonism | 2 | 10 | NA | 2 |
| DNAJC13 | Late-onset Parkinson’s disease; essential tremor | 1 | NA | NA | NA |
| DNAJC16 | Hereditary spastic paraplegia | NA | NA | NA | NA |
| DNAJC19 | 3-Methylglutaconic aciduria type V | NA | 4 | 1 | 2 |
| DNAJC21 | Bone marrow failure syndrome 3; tongue abnormality, acute myeloid leukemia, cognitive impairment, pancytopenia, pectus excavatum, short stature, and webbed neck | 2 | 8 | NA | NA |
| DNAJC28 | Delayed speech and language, generalized hypotonia, intellectual disability, seizures, and optic atrophy | NA | NA | NA | NA |
| DNAJC30 | Leber hereditary optic neuropathy | 3 | NA | 1 | NA |
| GAK | Parkinson’s disease | NA | NA | NA | NA |
| SACS | Spastic ataxia of Charlevoix–Saguenay; Spastic paraplegia | 18 | 155 | 17 | 188 |
Previous disease associations were based on reports of variant pathogenicity in the ClinVar database. NA: no variants were reported with the pathogenicity classification in ClinVar; LoF: putative loss-of-function variants, including essential splice site, frameshift, stop gain, and stop loss variants.