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Table 3 Genes identified with both large and small-effect mutations that affect stature and skeletal formation in humans

From: Genetic architecture of body size in mammals

Gene OMIM phenotypes associated with the gene GWASs identifying the gene
  Number Example stature phenotypea Number Reference(s)
ACAN (aggrecan) 3 Spondyloepimetaphyseal dysplasia, aggrecan type (-) (OMIM 612813) 4 [7, 108110]
ADAMTS10 (ADAM metallopeptidase with thrombospondin type 1 motif, 10) 1 Weill-Marchesani syndrome 1, recessive (-) (OMIM 277600) 2 [109, 111]
ARSE (arylsulfatase E) (chondrodysplasia punctata 1) 1 Chondrodysplasia punctata, X-linked recessive (-) (OMIM 302950) 2 [110, 112]
BBS1 (Bardet-Biedl syndrome 1) 1 Bardet-Biedl syndrome 1 (-) (OMIM 209900) 1 [109]
BBS7 (Bardet-Biedl syndrome 7) 1 Bardet-Biedl syndrome 7 (-) (OMIM 209900) 1 [109]
BRCA2 (breast cancer 2, early onset) 9 Fanconi anemia, complementation group D1 (-) (OMIM 605724) 1 [7]
COL11A1 (collagen, type XI, alpha 1) 4 Fibrochondrogenesis (-) (OMIM 228520) 1 [113]
CYP19A1 (cytochrome P450, family 19, subfamily A, polypeptide 1) 2 Aromatase deficiency (-) (OMIM 613546) 3 [7, 109, 114]
DYM (dymeclin) 2 Smith-McCort dysplasia (-) (OMIM 607326) 4 [7, 108, 109, 112]
EIF2AK3 (eukaryotic translation initiation factor 20alpha kinase 3) 1 Wolcott-Rallison syndrome (-) (OMIM 226980) 2 [7, 109]
EXT1 (exostosin 1) 2 Exostoses, multiple, type 1 (-) (OMIM 133700) 1 [115]
FANCC (Fanconi anemia, complementation group C) 1 Franconi anemia, complementation group C (-) (OMIM 227645) 1 [7]
FANCE (Fanconi anemia, complementation group E) 1 Franconi anemia, complementation group E (-) (OMIM 600901) 1 [7]
FBN2 (fibrillin 2) 1 Contractural arachnodactyly, congenital (+) (OMIM 121050) 1 [110]
FGFR3 (fibroblast growth factor receptor 2) 13 Achondroplasia (-) (Table 1) 1 [7]
FLNB (fibamin B, beta) 5 Larsen syndrome (-) (OMIM 150250) 1 [116]
GALNS (galactosamine (N-acetyl)-6-sulfate sulfatase) 1 Mucopolysaccharidosis IVA (-) (OMIM 253000) 1 [7]
GDF5 (growth differentiation factor 5) 8 Acromesomelic dysplasia, Hunter-Thompson type (-) (OMIM 201250) 1 [7]
GH1 (growth hormone 1) 4 Growth hormone deficiency, isolated, type IA (-) (OMIM 262400) 1 [109]
GHR (growth hormone receptor) 4 Laron dwarfism (-) (OMIM 262500) 1 [109]
GHSR (growth hormone secretagogue receptor) 1 Short stature (-) (OMIM 604271) 2 [7, 109]
HMGA2 (high-mobility group AT-hook 2) 1 Leiomyoma, uterine, somaticb (-) (OMIM 150699) 9e [7, 10112, 114, 117, 118]
IHH (Indian hedgehog) 2 Acrocapitofemoral dysplasia (-) (OMIM 607778) 2 [7, 111]
KCNJ2 (potassium inwardly-rectifying channel, subfamily J, member 2) 3 Atrial fibrillation, familial, 9 (-) (OMIM 613980) 1 [7]
PTCH1 (patched 1) 3 Basal cell nevus syndromec (-) (OMIM 109400) 3e [7, 108, 109, 119, 120]
RNF135 (ring finger protein 135) 1 Macrocephaly, macrosomia, facial dysmorphism syndrome (+) (OMIM 614192) 1 [7]
RPL5 (ribosomal protein L5) 1 Diamond-Blackfan anemia 6d (-) (OMIM 612561) 1 [7]
RUNX2 (runt-related transcription factor 2) 2 Cleidocranial dysplasia (-) (OMIM 119600) 1 [7]
SLC39A13 (solute carrier family 39 (zinc transporter), member 13) 1 Spondylocheirodysplasia, Ehlers-Danlos syndrome-like (-) (OMIM 612350) 1 [7]
TBX15 (T-box 15) 1 Cousin syndrome (-) (OMIM 260660) 2 [108, 121]
  1. Genes with mutation of large effect are from the 241 genes identified by Lango Allen et al. [7] from the Online Mendelian Inheritance in Man database. Surveyed genome-wide association studies are listed in Table S1 in Additional file 1.
  2. aThe effect of the mutation on stature phenotypes indicate reduced (-) or increased (+) height for carriers of the mutation; bmutation identified for uterine leiomyomata associated with 1.5 cm decrease in height (that is, 0.21 standard deviation (SD) units, assuming SD for height is 7 cm) [121, 122]; cheterogeneous condition causing skeletal abnormalities and predisposition to tumors, and there is one report of PTCH1 duplication causing microcephaly [120]; dDiamond-Blackfan anemia is a genetically heterogeneous condition causing growth failure and RPL5 is associated with the disease; evalidated gene in cattle [31].