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Table 2 Candidate genes with evidence for functional involvement in skeletal biology

From: Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual

Signal Genea Gene Ontology or KEGG term Mendelian disease (OMIM ID)b Human phenotype Mouse phenotypec Selected references
2 FOSL2 Osteoclast differentiation NA NA Abnormal osteoblast and osteoclast morphology and physiology; abnormal bone morphology; decreased bone mineralization; etc. Bozec (Nature 2008)
3 FOXP1 Osteoclast differentiation and development NA NA Abnormal osteoclastogenesis and bone resorption Zhao (Dev Biol 2015)
4 COL8A1    Downregulated in aged osteoblasts Slightly elevated bone mineral content Zhang (Biochem Biophys Res Comm 2018)
5 WWTR1 (TAZ) Osteoclast differentiation, mesenchymal cell differentiation NA NA Abnormal skeleton morphology and bone ossification; decreased body size Hong (Science 2005)
8 IL17A [P] Positive regulation of osteoclast development NA NA NA Kotake (Clin Invest 1999)
9 TBXAS1 NA Ghosal heamtodiaphyseal dysplasia (231095) Increased bone density NA Genevieve (Nat Genet 2008)
15 BLNK Osteoclast differentiation NA NA NA Shinohara (Cell 2008)
18 SLC9A3R1 (NHERF) Wnt signaling pathway Hypophosphatemic nephrolithiasis/osteoporosis-2 (612287) Low bone mineral density Decreased bone mineral content and density Karim (NEJM 2008)
19 GRB2 [P] Osteoclast differentiation NA NA Abnormal mandible morphology Levy-Apter (J Biol Chem 2014)
21 TGFB1 Osteoclast differentiation Camurati-Engelmann disease (131300) Cortical thickening of the diaphyses of the long bones; some patients also show involvement of the skull; increased bone mineral density; osteopenia Abnormal bone ossification; decreased osteoblast cell number; etc. Kinoshita (Nat Genet 2000); Gao (Proc Natl Acad Sci 2004)
22–23 NRIP1 NA NA Differentially expressed in low and high BMD samples; may interact with ESR1 NA Morón (Bone 2006); Li (Bone Joint Res 2016)
24 CITED1 Negative regulation of osteoblast differentiation NA NA NA Yang (Endocrinology 2008)
25–26 ATP7A NA Menkes disease (309400), Occipital horn syndrome (304150) Defective collagen cross-linking resulting in osteoporosis and pathological fracture Abnormal skeleton morphology; osteoarthritis Kim (Stem Cell Res Ther 2015)
S2 HDAC4 Osteoblast differentiation and development NA NA Abnormal bone ossification; abnormal osteoblast cell number; skeletal phenotype; etc. Vega (Cell 2004)
  TWIST2 Negative regulation of osteoblast differentiation Ablepharon-macrostomia syndrome (200110); Barber-Say syndrome (209885) Premature osteoblast differentiation, growth retardation Abnormal osteoblast differentiation Bialek (Dev Cell 2004)
S3 TET2 [P] NA Myelodysplastic syndrome, somatic (614286) NA Osteopetrosis, reduced osteoclast number Chu (Genomics, Proteomics & Bioinf. 2018); Yang (Nat Comm 2018)
S6 TEAD4 Skeletal system development NA NA NA Matsumoto (J Clin Invest 2016);
  TULP3 [P] Bone development NA NA Abnormal vertebrae morphology and development Patterson (HMG 2009)
S7 PRKD1 Positive regulation of osteoclast development NA NA Reduced bone mineral density; decreased trabecular thickness Bollag (Mol Cell Endocrinol 2018)
S9 GNA11 Skeletal system development Hypocalcemia (615361); hypocalciuric hypercalcemia (145981) Altered calcium levels; short stature Decreased bone mineral content and density Nesbit (NEJM 2013)
S9 AES (TLE5) Skeletal system development NA NA NA Zhao (BBRC 2017)
S11 SOX11 Positive regulation of osteoblast differentiation Coffin-Siris syndrome 9 (615866) Abnormal skeletal morphology Abnormal bone mineralization and ossification; abnormal lumbar vertebrae morphology Tsurusaki (Nat Commun 2014)
S12 SLIT3 NA NA Higher circulating levels associated with higher bone mass in postmenopausal women Low bone mass Kim (J Clin Invest 2018)
S13 SMC3 NA Cornelia de Lange syndrome 3 (610759) Growth retardation Decreased bone mineral content Andrade (Horm Res Paediatr 2017)
  1. a[P] Genes implicated by promoter-interaction map
  2. bMendelian disease genes from the Online Mendelian Inheritance in Man (OMIM) database (
  3. cMouse phenotypes from the Mouse Genome Informatics database (