Table 1.
A summary of the functional studies of the C-terminal mutations in RUNX2.
| Genetic variant | Amino acid change | Cell type | Localization | Transactivation | Protein expression | Gene expression and osteogenic differentiation | Articles reporting the variants in CCD patients | Functional studies |
|---|---|---|---|---|---|---|---|---|
| PST region | ||||||||
| c.739delA | p.Ser247Valfs*3 | HEK-293T | Nucleus and cytoplasm | High | Truncated | NA | 7 | This study |
| c.739delA | p.Ser247Valfs*3 | aBMSC | Nucleus and cytoplasm | NA | NA |
↓ RUNX2, OCN, COL1A1; ~ ALP (GM) ↓ RUNX2, OCN; ↑ COL1A1, ALP ↓ ARS staining |
7 | This study |
| c.774_779del AGTAGGinsGA | p.Val259Metfs*11π | HEK-293T | Nucleus | Low | Truncated | NA | 18 | 18 |
| c.835C > T | p.Pro279Ser | HEK-293T | Nucleus and cytoplasm | Normal | Normal | NA | None | This study |
| c.838C > T | p.Gln280* | NIH-3T3 | Nucleus and cytoplasm | Half | NA | NA | 19† | 19† |
| c.859G > A | p.Asp287Asn | HEK-293T | Nucleus | Normal | Normal | NA | 16,17 | This study |
| c.887dup | p.Trp297Valfs*4θ | CHO | Nucleus and cytoplasm | NA | NA | NA | 20 | 20 |
| c.897 T > G | p.Tyr299* | Fibroblasts | NA | NA | Truncated | ↓ SPARC, P53, and PTEN | 21 | 21 |
| c.901C > T | p.Gln301* | HEK-293T | Nucleus and cytoplasm | High | Truncated | NA | 7 | This study |
| c.1019del | p.Ser340* | Fibroblasts, cMSCs | NA | NA | Truncated | ↓ SPARC, P53, and PTEN | 21 | 21 |
| c.1081C > T | p.Gln361* | HEK-293T | Nucleus and cytoplasm | High | Truncated | NA | 7 | This study |
| c.1085C > T | p.Ala362Val# | NIH-3T3 | Nucleus and cytoplasm | Half | NA | NA | 19† | 19† |
| c.1096G > T | p.Glu366* | HEK-293T | Nucleus and cytoplasm | High | Truncated | NA | 22 | This study |
| c.1096G > T | p.Glu366* | DPCs | Nucleus and cytoplasm | NA | Truncated | NA | 22 | 22 |
| c.1111dup | p.Ser371Phefs*14 | HEK-293T | Nucleus and cytoplasm | Low | Truncated | NA | 23 | 23 |
| c.1119dup | p.Arg374Glnfs*11 | BMMSCs, DPSCs | NA | NA | Truncated |
↑ RUNX2, ALP, ~ OCN (GM) ↓ RUNX2, ALP, OCN (OM) ↓ ARS staining |
24 | 24 |
| NMTS region | ||||||||
| c.1171C > T | p.Arg391* | NIH 3T3, COS7 | NA | Low | Truncated | NA | 25–35† | 35† |
| c.1199dup | p.Tyr400* | HEK-293T | Nucleus | Low | Truncated | NA | 18 | 18 |
| c.1228dup | p.Leu410Profs*80 | Growth plate RNA | NA | NA | NA |
↓ RUNX2, COL10A1, MMP13, VEGF ↑ RUNX3 |
36 | 36 |
| c.1259C > A | p.Thr420Asn | HEK-293T | Nucleus and cytoplasm | High | Normal | NA | 16 | This study |
| c.1384G > T | p.Gly462* | C2C12 | NA | Low | Truncated | ↓ OCN, ALP, COL1A1, MMP13, BSP, OPN; ↓ ARS staining | 33 | 33 |
| VWRPY region | ||||||||
| c.1550del | p.Trp518Glyfs*60 | HEK-293T | Nucleus | Low | Elongated | NA | 37 | 37 |
aBMSC alveolar bone mesenchymal stem cells, ARS alizarin red S, cMSCs circulating mesenchymal stem cells, DPCs dental pulp cells, GM general media, NA not applicable, OM osteogenic media.
↓, ↑, ~ , decreased, increased, comparable level compared with controls, respectively.
#predicted splicing (https://varseak.bio/index.php), θp.Val259Metfs*11 (p.258 fs reported in an original article), πp.Trp297Valfs*4 (p.296 fs reported in an original article), †NM_001024630.4 (NM_001369405.1 reported in an original article).