The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 526, 68–74 (2015).

Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434–443 (2020).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Mendell, J. T. & Dietz, H. C. When the Message Goes Awry. Cell 107, 411–414 (2001).

CAS  PubMed  Article  Google Scholar 

McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, M. Online Mendelian Inheritance in Man, OMIM®. https://omim.org/.

Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Varadi, M. et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. https://doi.org/10.1093/nar/gkab1061 (2021).

UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 47, D506–D515 (2019).

Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248–249 (2010).

CAS  PubMed  PubMed Central  Article  Google Scholar 

López-Ferrando, V., Gazzo, A., de la Cruz, X., Orozco, M. & Gelpí, J. L. PMut: a web-based tool for the annotation of pathological variants on proteins, 2017 update. Nucleic Acids Res. 45, W222–W228 (2017).

PubMed  PubMed Central  Article  CAS  Google Scholar 

Sim, N. L. et al. SIFT web server: Predicting effects of amino acid substitutions on proteins. Nucleic Acids Res. 40, W452–7 (2012).

Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57 (2009).

CAS  Article  Google Scholar 

Boldt, K. et al. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nat. Commun. 7, 11491 (2016).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Yan, J. et al. The 3M Complex Maintains Microtubule and Genome Integrity. Mol. Cell 54, 791–804 (2014).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Hanson, D., Murray, P. G., Black, G. C. M. & Clayton, P. E. The Genetics of 3-M Syndrome: Unravelling a Potential New Regulatory Growth Pathway. Horm. Res. Paediatr. 76, 369–378 (2011).

CAS  PubMed  Article  Google Scholar 

Mészáros, B., Erdős, G. & Dosztányi, Z. IUPred2A: context-dependent prediction of protein disorder as a function of redox state and protein binding. Nucleic Acids Res. 46, W329–W337 (2018).

PubMed  PubMed Central  Article  CAS  Google Scholar 

Wang, P. et al. Impaired plasma membrane localization of ubiquitin ligase complex underlies 3-M syndrome development. J. Clin. Invest. 129, 4393–4407 (2019).

PubMed  PubMed Central  Article  Google Scholar 

Hanson, D. et al. Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signalling. J. Mol. Endocrinol. 49, 267–275 (2012).

CAS  PubMed  Article  Google Scholar 

Nie, J. et al. Ankyrin Repeats of ANKRA2 Recognize a PxLPxL Motif on the 3M Syndrome Protein CCDC8. Structure 23, 700–712 (2015).

CAS  PubMed  Article  Google Scholar 

Hornbeck, P. V. et al. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 43, D512–D520 (2015).

CAS  PubMed  Article  Google Scholar 

Scoville, D. W., Kang, H. S. & Jetten, A. M. GLIS1-3: emerging roles in reprogramming, stem and progenitor cell differentiation and maintenance. Stem Cell Investig. 4, 80–80 (2017).

PubMed  PubMed Central  Article  CAS  Google Scholar 

Lee, S.-Y. et al. Glis family proteins are differentially implicated in the cellular reprogramming of human somatic cells. Oncotarget 8, 77041–77049 (2017).

PubMed  PubMed Central  Article  Google Scholar 

Masetti, R., Bertuccio, S. N., Pession, A. & Locatelli, F. CBFA2T3-GLIS2-positive acute myeloid leukaemia. A peculiar paediatric entity. Br. J. Haematol. 184, 337–347 (2019).

CAS  PubMed  Article  Google Scholar 

Hara, Y. et al. Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup. Br. J. Haematol. 188, 528–539 (2020).

CAS  PubMed  Article  Google Scholar 

Palencia-Campos, A. et al. GLI1 inactivation is associated with developmental phenotypes overlapping with Ellis–van Creveld syndrome. Hum. Mol. Genet. 26, 4556–4571 (2017).

CAS  PubMed  Article  Google Scholar 

Twigg, S. R. F. et al. Gain-of-Function Mutations in ZIC1 Are Associated with Coronal Craniosynostosis and Learning Disability. Am. J. Hum. Genet. 97, 378–388 (2015).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Roessler, E. et al. The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism. Hum. Mutat. 30, E541–E554 (2009).

PubMed  PubMed Central  Article  Google Scholar 

Hildebrandt, F., Attanasio, M. & Otto, E. Nephronophthisis: Disease Mechanisms of a Ciliopathy. J. Am. Soc. Nephrol. 20, 23–35 (2009).

CAS  PubMed  Article  Google Scholar 

Halbritter, J. et al. Identification of 99 novel mutations in a worldwide cohort of 1,056 patients with a nephronophthisis-related ciliopathy. Hum. Genet. 132, 865–884 (2013).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Tuladhar, S. & Kanneganti, T.-D. NLRP12 in innate immunity and inflammation. Mol. Asp. Med. 76, 100887 (2020).

CAS  Article  Google Scholar 

Zhang, X., Nan, H., Guo, J. & Liu, J. NLRP12 reduces proliferation and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by regulating the NF-κB and MAPK pathways. Eur. Cytokine Netw. 32, 15–22 (2021).

PubMed  Article  CAS  Google Scholar 

Jeru, I. et al. Mutations in NALP12 cause hereditary periodic fever syndromes. Proc. Natl Acad. Sci. 105, 1614–1619 (2008).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Perez, J. M. et al. β1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Nat. Med. 9, 1300–1305 (2003).

CAS  Article  Google Scholar 

Riis-Vestergaard, M. J. et al. Beta-1 and Not Beta-3 Adrenergic Receptors May Be the Primary Regulator of Human Brown Adipocyte Metabolism. J. Clin. Endocrinol. Metab. 105, e994–e1005 (2020).

Article  Google Scholar 

Inoue, A. et al. Illuminating G-Protein-Coupling Selectivity of GPCRs. Cell 177, 1933–1947.e25 (2019).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Yao, J., Subramanian, C., Rock, C. O. & Jackowski, S. Human pantothenate kinase 4 is a pseudo-pantothenate kinase. Protein Sci. 28, 1031–1047 (2019).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Zhou, B. et al. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat. Genet. 28, 345–349 (2001).

CAS  PubMed  Article  Google Scholar 

El-Gebali, S. et al. The Pfam protein families database in 2019. Nucleic Acids Res. 47, D427–D432 (2019).

CAS  PubMed  Article  Google Scholar 

Hayflick, S. J. et al. Genetic, Clinical, and Radiographic Delineation of Hallervorden–Spatz Syndrome. N. Engl. J. Med. 348, 33–40 (2003).

CAS  PubMed  Article  Google Scholar 

Wu, Z., Li, C., Lv, S. & Zhou, B. Pantothenate kinase-associated neurodegeneration: insights from a Drosophila model. Hum. Mol. Genet. 18, 3659–3672 (2009).

CAS  PubMed  Article  Google Scholar 

Van Kim, C., Le, Colin, Y. & Cartron, J.-P. Rh proteins: Key structural and functional components of the red cell membrane. Blood Rev. 20, 93–110 (2006).

PubMed  Article  CAS  Google Scholar 

Gruswitz, F. et al. Function of human Rh based on structure of RhCG at 2.1 A. Proc. Natl Acad. Sci. 107, 9638–9643 (2010).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Wagner, F. F. et al. Molecular basis of weak D phenotypes. Blood 93, 385–393 (1999).

CAS  PubMed  Article  Google Scholar 

Taillandier, A. et al. Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia. Mutations in brief no. 217. Hum. Mutat. 13, 171–172 (1999).