Fig. 2
From protein to disease: tertiary structure of NBAS, localization of missense variants and in-frame deletions, disorder prediction, and phenotypic patterns of the three domain-related subgroups. (a) Tertiary structure modeling and disorder predictions of NBAS. Structural predictions were determined using the HHpred suite. The region 86–446 was modeled from the A chain of COMPASS histone methyltransferase in yeast (PDB: 6CHG_A; probability: 98.5; p value: 9.8e-12), and the region 722–1369 was modeled from the D chain of DslI transport complex in yeast (PDB: 3K8P_D; probability: 100; p value: 6.9e-66). Red inverted triangles indicate predicted regions with high disorder scores (1–41, 459–475, 644–657, 1382–1398, 1933–1947). The disorder score for the entire protein was determined using the IUPRED server. Missense variants and in-frame deletions are indicated as gray dots on the gene as well as gray Calpha spheres in the two modeled domains as best as possible. (b) Phenotypic patterns of the three subgroups β-propeller, Sec39 and C-terminal. (c) Facial phenotypes (composite faces). All patients tend to present thicker eyebrows and broader columella, but only patients attributed to the C-terminal group significantly differ from their controls, presenting triangular face, wide palpebral fissures, deep set eyes and thin upper lip vermilion, thick eyebrows, short philtrum, and small mouth. AUC area under the curve, ROC receiver operating characteristic.
