Table 3.
Transcriptional profiling of genes underlying peripheral neuropathies.
| Gene Symbol | Gene Name | Disease Phenotype | TRPV1 Lineage | Non-TRPV1 Lineage | DRG | Sciatic | DRG | Tibial |
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| Mouse | Rat | Human | ||||||
|
|
||||||||
| Proteostasis/folding | ||||||||
| Prnp | Prion protein | HSAN + dementia | 149.2 | 214.0 | 281.3 | 194.9 | 263.7 | 93.2 |
| Hspb8 | Heat shock protein, beta 8 | CMT2L | 184.9 | 81.6 | 92.9 | 4.4 | 31.3 | 7.1 |
| Cct5 | T-complex protein 1 subunit epsilon | HSN+SPG | 92.6 | 78.6 | 111.4 | 66.9 | 43.9 | 31.0 |
| Dnajb2 | (Hsp40) homolog, subfamily B, member 2 | DSMA5 | 23.1 | 30.1 | 60.0 | 38.3 | 32.2 | 57.5 |
| Trim2 | Tripartite motif containing 2 | CMT2 | 37.9 | 58.1 | 28.9 | 4.0 | 55.6 | 5.5 |
| Channel | ||||||||
| Gjb1 | Gap junction protein, beta-1, 32kD (connexin 32) | CMTX | 0.8 | 10.7 | 6.5 | 33.2 | 1.3 | 11.8 |
| Atp7a | ATPase, Cu(2+)-transporting | CMT2-like | 2.3 | 2.5 | 3.6 | 2.7 | 3.4 | 2.2 |
| Transcriptional regulation | ||||||||
| Prdm12 | PR Domain Containing 12 | CIPS | 136.4 | 21.8 | 29.6 | 0.0 | 11.3 | 0.0 |
| Egr2 | Early growth response 2 | CMT1 | 3.3 | 8.4 | 8.8 | 27.4 | 5.0 | 30.2 |
| Med25 | Mediator of RNA polymerase II transcription, subunit 25 | CMT2B2 | 20.8 | 13.1 | 18.6 | 9.2 | 3.7 | 19.5 |
| Ikbkap | Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase | HSAN3 | 7.7 | 9.3 | 14.1 | 8.1 | 11.5 | 14.3 |
| Dnmt1 | DNA (cytosine-5-)-methyltransferase 1 | HSN1E | 7.0 | 5.8 | 3.9 | 4.4 | 5.1 | 11.6 |
| Setx | Senataxin | SCAR1 or ALS4 | 4.2 | 5.7 | 4.3 | 4.4 | 10.7 | 9.6 |
| Ighmbp2 | Immunoglobulin mu binding protein 2 | DSMA1 | 1.8 | 2.9 | 9.6 | 3.2 | 3.1 | 6.4 |
| Ctdp1 | Carboxy-terminal domain, RNA polymerase II, polypeptide A phosphatase, subunit 1 | CMT1 | 3.7 | 3.4 | 4.1 | 5.0 | 2.5 | 6.0 |
| Hoxd10 | Homeo box-D10 | CMT + CVT | 1.1 | 1.2 | 1.1 | 0.1 | 1.2 | 1.5 |
| Cytoskeletal | ||||||||
| Nefl | Neurofilament, light polypeptide | CMT2E | 535.7 | 2808.3 | 3380.5 | 3.1 | 1211.5 | 0.8 |
| Prx | Periaxin | CMT1 | 17.3 | 132.2 | 113.5 | 675.8 | 29.2 | 337.4 |
| Reep1 | Receptor accessory protein 1 | HMN5B or SPG31 | 169.9 | 130.4 | 153.6 | 1.4 | 212.6 | 1.1 |
| Atl1 | Atlastin-1 | HSN1D | 72.2 | 55.3 | 93.0 | 8.9 | 91.0 | 9.0 |
| Dst | Dystonin | HSAN4, lethal | 34.8 | 65.9 | 87.8 | 25.7 | 81.3 | 19.0 |
| Fbln5 | Fibulin 5 | CMT1 + | 7.2 | 19.3 | 36.1 | 33.7 | 84.6 | 60.9 |
| Lmna | Lamin A | CMT2B1 | 30.1 | 28.2 | 34.9 | 57.8 | 37.7 | 82.9 |
| Tfg | TRK-fused gene | CMT2 | 51.4 | 51.6 | 48.6 | 25.8 | 52.1 | 21.0 |
| Fgd4 | FYVE, RhoGEF, and PH domain-containing protein 4 | CMT4H | 1.4 | 2.2 | 8.6 | 0.0 | 7.2 | 7.5 |
| Inf2 | Inverted formin 2 | CMTDIE | 8.1 | 16.5 | no data | no data | 21.0 | 95.8 |
| Gan | Gigaxonin | GAN | 4.8 | 3.9 | 7.6 | 2.2 | 1.9 | 0.7 |
| Axonal transport and trafficking | ||||||||
| Kif5a | Kinesin heavy chain isoform 5A | CMT2 | 234.8 | 168.4 | 257.5 | 5.4 | 166.9 | 4.5 |
| Kif1b | Kinesin family member 1B | CMT2A1 | 98.8 | 165.7 | 183.6 | 21.0 | 43.1 | 8.9 |
| Hspb1 | Heat shock protein, beta 1 | CMT2F | 32.1 | 42.7 | 183.4 | 37.6 | 54.4 | 141.6 |
| Kif1a | Kinesin family member 1A | HSN2C or SPG30 | 168.7 | 170.3 | 180.2 | 60.1 | 59.9 | 24.6 |
| Dctn1 | Dynactin-1 | HMN7B | 155.9 | 114.6 | 140.5 | 29.1 | 85.8 | 29.6 |
| Bscl2 | Berardinelli-Seip congenital lipodystrophy 2 | CMT2D-like | 49.9 | 38.3 | 37.2 | 14.1 | 146.0 | 1.9 |
| Dync1h1 | Dynein, cytoplasmic, heavy chain 1 | CMT2O | 67.9 | 85.8 | 117.0 | 32.5 | 90.2 | 33.6 |
| Fam134b | Family with sequence similarity 134, member B | HSAN2B/1B | 38.9 | 31.7 | 56.3 | 42.9 | 42.0 | 13.8 |
| Myh14 | Myosin, heavy chain 14, non-muscle | PNMHH | 8.7 | 23.5 | 17.6 | 26.3 | 7.5 | 12.0 |
| Dnm2 | Dynamin-2 | CMT2 | 15.1 | 16.3 | 16.1 | 17.4 | 11.9 | 26.3 |
| Bicd2 | Bicaudal D homolog 2 | SMALED | 14.1 | 12.4 | 23.2 | 23.6 | 9.7 | 9.9 |
| Cltcl1 | Clathrin heavy chain 22 | CIPS + touch insensitive | N.O. | N.O. | N.O. | N.O. | 5.1 | 6.1 |
| Endosomal sorting and cell signaling | ||||||||
| Ndrg1 | N-myc downstream-regulated gene 1 | CMT4D | 57.6 | 174.0 | 164.0 | 659.4 | 162.9 | 418.3 |
| Rab7a | Ras-associated protein RAB7A | CMT2B | 180.8 | 117.0 | 105.6 | 103.9 | 116.5 | 123.0 |
| Ntrk1 | Neurotrophic tyrosine kinase, receptor, type 1 | CIPA or HSAN4 | 85.2 | 73.1 | 65.1 | 0.3 | 32.2 | 0.3 |
| Gnb4 | Guanine nucleotide binding protein (G protein), beta polypeptide 4 | CMTD1F | 68.0 | 8.1 | 22.2 | 12.0 | 15.0 | 6.3 |
| Mtmr2 | Myotubularin-related protein 2 | CMT4B1 | 20.1 | 26.6 | 30.4 | 45.7 | 17.6 | 8.9 |
| Litaf | LPS-induced TNFA factor | CMT1C | 13.0 | 7.2 | 15.9 | 36.1 | 32.1 | 39.2 |
| Lrsam1 | Leucine rich repeat and sterile alpha motif containing 1 | CMT2P | 34.5 | 35.1 | 23.8 | 9.8 | 9.6 | 7.8 |
| Wnk1 | WNK lysine deficient protein kinase 1 | HSAN2A | 20.0 | 27.0 | 20.8 | 22.5 | 24.5 | 19.9 |
| Sbf2 | SET binding factor 2 (MTMR13) | CMT4B2 | 4.1 | 8.1 | 8.3 | 26.8 | 9.0 | 12.8 |
| Fig4 | SAC domain-containing inositol phosphatase | CMT4J | 25.1 | 16.6 | 14.9 | 21.8 | 14.0 | 6.6 |
| Sbf1 | SET binding factor 1 (MTMR5) | CMT1 | 21.7 | 16.9 | 20.3 | 10.3 | 8.6 | 23.6 |
| Sh3tc2 | SH3 domain and tetratricopeptide repeats 2 | CMT1 | 0.6 | 3.5 | 6.0 | 18.8 | 1.2 | 4.8 |
| Plekhg5 | Pleckstrin homology domain containing, family G member 5 | RI-CMT | 1.6 | 8.3 | 4.2 | 12.2 | 4.4 | 16.3 |
| Chm | Choroideremia (Rab escort protein 1) | CMT1B | 8.9 | 8.6 | 10.0 | 4.8 | 9.9 | 3.0 |
| Mitochondrial | ||||||||
| MT-Atp6 Mitochondrially encoded ATP synthase 6 | CMT2 | no data | no data | 7829.8 | 8726.0 | no data | no data | |
| Hk1 | Hexokinase 1 | CMT1 | 85.6 | 76.0 | 82.1 | 28.7 | 67.0 | 17.6 |
| Mfn2 | Mitofusin 2 | CMT2A2 | 50.4 | 47.7 | 61.8 | 20.2 | 27.8 | 24.5 |
| Gdap1 | Ganglioside-induced differentiation-associated protein 1 | CMT2H/K | 34.5 | 35.6 | 39.0 | 1.1 | 33.4 | 5.9 |
| Pdk3 | Pyruvate dehydrogenase kinase, isozyme 3 | CMTX6 | 10.8 | 21.3 | 13.6 | 4.9 | 13.9 | 2.7 |
| Aifm1 | Apoptosis-inducing factor 1 | CMTX | 10.8 | 12.1 | 15.0 | 7.2 | 7.8 | 7.1 |
| Dhtkd1 | Dehydrogenase E1 and transketolase domain containing 1 | CMT2 | 0.3 | 1.0 | 2.8 | 4.4 | 5.4 | 8.7 |
| Myelin sheath | ||||||||
| Mpz | Myelin protein zero | CMT1B | 244.7 | 3387.1 | 3638.5 | 20467.3 | 228.0 | 2057.8 |
| Pmp22 | Peripheral myelin protein-22 | CMT1A | 384.7 | 1334.2 | 1107.4 | 11105.4 | 540.3 | 1329.1 |
| Plp1 | Proteolipid protein 1 | CMT1A | 66.1 | 188.3 | 176.4 | 439.7 | 311.9 | 210.9 |
| Nucleotide and tRNA Synthesis | ||||||||
| Aars | Alanyl-tRNA synthetase | CMT2N | 23.2 | 38.3 | 86.4 | 25.1 | 32.9 | 43.3 |
| Gars | Glycyl-tRNA synthetase | CMT2D | 81.9 | 64.4 | 9.3 | 23.0 | 53.7 | 27.3 |
| Hars | Histidyl-tRNA synthetase | CMT2 | 50.5 | 50.7 | 52.0 | 15.4 | 32.2 | 16.9 |
| Yars | Tyrosyl-tRNA synthetase | CMTDIC | 25.1 | 29.8 | 41.7 | 10.4 | 16.5 | 9.2 |
| Kars | Lysyl tRNA synthetase | CMTRIB | 29.1 | 29.6 | 36.4 | 30.4 | 34.9 | 35.9 |
| Prps1 | Phosphoribosyl pyrophosphate synthetase 1 | CMTX5 | 24.1 | 19.6 | 32.7 | 10.6 | 33.0 | 20.2 |
| Mars | Methionyl-TRNA synthetase | CMT2 | 8.9 | 9.4 | 24.2 | 15.6 | 21.7 | 27.1 |
| Very low expression | ||||||||
| Ngf | Nerve growth factor | HSAN5 | 0.3 | 0.5 | 0.3 | 1.0 | 0.6 | 7.3 |
| Slc5a7 | Solute carrier family 5 (sodium/choline cotransporter), member 7 | HMN7A | 1.3 | 0.1 | 1.0 | 0.1 | 0.6 | 0.0 |
| Trpv4 | Transient receptor potential cation channel, subfamily V, member 4 | CMT2C | 0.8 | 0.4 | 0.2 | 0.9 | 0.1 | 0.6 |
| Hspb3 | Heat shock protein, beta 3 | HMN2C | 0.1 | 0.1 | 0.4 | 0.1 | 0.0 | 0.2 |
| Other | ||||||||
| Hint1 | Histidine triad nucleotide binding protein 1 | NMAN | 245.8 | 274.1 | 97.0 | 54.3 | 228.8 | 62.3 |
| Sptlc2 | Serine palmitoyltransferase, long chain base subunit 2 | HSAN1C | 11.1 | 14.8 | 20.2 | 31.7 | 13.8 | 8.4 |
| Sptlc1 | Serine palmitoyltransferase, long chain base subunit 1 | HSAN1A | 8.3 | 8.5 | 12.0 | 15.3 | 26.7 | 13.3 |
Note: Abbreviations are given for general diseases but not for subtypes. Charcot-Marie-Tooth is classically diagnosed in two broad categories: those affecting the myelin sheath (CMT1) and those affecting the neuron (CMT2) as determined by slow or normal nerve conduction velocity, respectively. TRPV1 lineage and non-lineage datasets are re-analyzed from Goswami, et al 2014. TRPV1 lineage are sorted from the DRG and include nociceptive sensory neurons as well as TH+ hair cells. TRPV1 non-lineage samples are cells remaining in the DRG after the Trpv1 promoter is used to drive a toxic gene product, which includes neurons not expressing TRPV1, as well as non-neural cells.
Abbreviations: N.O. - no ortholog; HSAN - hereditary sensory and autonomic neuropathy; CMT, Charcot-Marie Tooth; HSN - hereditary sensory neuropathy; SPG - spastic paraplegia; DSMA - distal spinal muscular atrophy; CIPS - congenital insensitivity to pain syndrome; SCA - spinocerebellar ataxia; ALS - amyotrophic lateral sclerosis; CVT - congenital vertical talus; HMN - hereditary motor neuropathy; GAN - giant axonal neuropathy; PNMHH - peripheral neuropathy, myopathy, hoarseness and hearing loss; SMALED - spinal muscular atrophy, lower extremity-predominant, autosomal dominant; CIPA - congenital insensitivity to pain with anhidrosis; NMAN - neuromyotonia and axonal neuropathy