Table 1.
A summary of disease-associated Nup coding variants.
| Nup | Coding Variant(s) | Disease | Experimental Observations | Refs. | |
|---|---|---|---|---|---|
| Cytoplasmic Filaments | AAAS (Aladin) | Q15K; H71fs * 92; W84X; R119*; Q145*; F157fs * 171; H160R; R230*; Q237*; S263P; R286*; W295*; R312*; V313A; S328fs * 362; V369fs * 382; S382fs * 413; Q387*; E398fs * 424; Q456*; Q456fs * 492; R342*; S463fs * 549; W474*; R478* | Triple-A syndrome (Allgrove syndrome) | Normal NPC structure and NTR localization, some mutations result in mislocalized AAAS (HeLa cells and patient-derived fibroblasts) | [234–237] |
| Gle1 | S70*; R697C | Amyotrophic Lateral Sclerosis (ALS) | Decreased mRNA levels, neuronal cell death (patient lymphoblast cells; zebrafish) | [225] | |
| T144_E145insPFQ; R569H; V617M; I684T | Lethal congenital contracture syndrome 1 (LCCS1) and lethal arthrogryposis with anterior horn cell disease (LAAHD) | Specific loss of Gle1 at the nucleus (patient-derived fibroblasts) | [238–240] | ||
| Nup88 | D434Y; R509*; E634del | Fetal akinesia deformation sequence | Impaired locomotive behavior, loss-of-function, disrupted interaction with other Nups, premature lethality (HeLa and C2C12 cells; zebrafish) | [241] | |
| Nup214 | R38C; L68del; D154G; P525Lfs *6; P387S | Encephalopathy and microcephaly (including IIAE9) | Decreased Nup214 and Nup88 at the nucleus, blocked NPC channel, abnormal nuclear morphology, impaired NCT, increased sensitivity to heat stress (patient-derived fibroblasts) | [242–244] | |
| Nup358 (RANBP2) | T585M; T653I; I656V | Acute necrotizing encephalopathy (ANE1) | Reduced interaction with COX11 (purified protein), impaired interactions with GW182/TNRC6 and associated miRNA pathway defects (HEK293T cells) | [245–247] | |
| Coat Nucleoporin Complex | Nup37 | R306* | Steroid-resistant nephrotic syndrome (SRNS) | Reduced mRNA and protein levels, co-depletion of Nup107 and Nup160, reduced NPC density, altered chromatin organization, deformed nuclei (patient-derived fibroblasts) | [248] |
| Nup85 | A477V; A581P; R645W | SRNS | Weakened interactions with Nup160, early lethality (HEK293T cells; zebrafish) | [248] | |
| Nup107 | M101I; D157Y; E360Gfs *6; D447N; D831A | Early-childhood-onset SRNS | Reduced Nup107 and Nup133 protein levels, reduced Nup107:Nup133 binding, mislocalized Nup107 (purified protein; patient-derived fibroblasts) | [249,250] | |
| M101I; E341Gfs *3; E710del; Y889C | SRNS | Reduced mRNA and protein levels, reduced interaction with Nup133, co-depletion of Nup37 and Nup160 (HEK293T and patient lymphoblastoid cells) | [248] | ||
| Nup133 | R231G; L1055S; S974R | SRNS | Reduced binding to Nup107 (HEK293T cells) | [248] | |
| Nup160 | E803K; R1173* | SRNS | Abnormal nuclear volume, some mutations affect NPC localization and nuclear morphology (Drosophila) | [251] | |
| Inner Ring | Nup93 | R388W; K442Nfs *14; G591V; Y629C | SRNS | Reduced localization to the nuclear envelope, fail to form NPCs, reduce interaction with Imp7 (HEK293 cells and cultured human podocytes) | [252] |
| Nup155 | R391H | Atrial fibrillation | Reduced accumulation at the nuclear envelope, reduced nuclear envelope permeability, inhibition of Hsp70 mRNA export, reduced Hsp70 expression (COS7 and HeLa cells) | [253] | |
| Nup188 | Y96*; Q113* | ‘Nup188 insufficiency syndrome’ | N/A | [254] | |
| I302Vfs *7; W630*; W1048*; Q1360*; R1678Pfs *13; | Brain malformation, dysmorphic features, visual impairment, heart anomalies, hypotonia, progressive microcephaly | Reduced Nup188 mRNA and protein levels, defective NCT for both canonical and non-canonical nuclear import (patient-derived fibroblasts) | [255] | ||
| Nup205 | F1995S | SRNS | Reduced interaction with Nup93 (cultured human podocytes) | [252] | |
| Central Channel | Nup54 | I358S; K376E; Q471del; Q472del; L474F | Infantile striatonigral degeneration | Proper localization, but reduced levels of Nup54, Nup62, and Nup58 (patient-derived fibroblasts) | [256] |
| Nup62 | Q391P | Recessive infantile bilateral striatal necrosis | Normal nuclear localization (U2OS and patient lymphoblastoid cells) | [257] | |
| Nuclear Basket | Nup50 | Q20C; F58fs; R45C; R72C; G114D; Y156C; P179A; K275E; R448W | ALS | Reduced Nup50 protein levels (patient lymphoblast cells) | [224] |
| TPR | V859_D870del; R2209* | Ataxia, microcephaly, and intellectual disability | Decreased TPR levels, decreased colocalization to NPCs, increase in NPC density, reduced nuclear mRNA levels (patient-derived fibroblasts) | [258] |
A table listing the known disease-associated Nup coding variants, including their subdomain within the nuclear pore complex, the specific coding variants, the associated diseases, experimental observations that have been made for the mutations, and references.