RUNX2_HUMAN
ID RUNX2_HUMAN Reviewed; 521 AA.
AC Q13950; O14614; O14615; O95181;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Runt-related transcription factor 2;
DE AltName: Full=Acute myeloid leukemia 3 protein;
DE AltName: Full=Core-binding factor subunit alpha-1;
DE Short=CBF-alpha-1;
DE AltName: Full=Oncogene AML-3;
DE AltName: Full=Osteoblast-specific transcription factor 2;
DE Short=OSF-2;
DE AltName: Full=Polyomavirus enhancer-binding protein 2 alpha A subunit;
DE Short=PEA2-alpha A;
DE Short=PEBP2-alpha A;
DE AltName: Full=SL3-3 enhancer factor 1 alpha A subunit;
DE AltName: Full=SL3/AKV core-binding factor alpha A subunit;
GN Name=RUNX2; Synonyms=AML3, CBFA1, OSF2, PEBP2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT CLCD
RP ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-84 INS, VARIANT 78-ALA--ALA-83 DEL,
RP AND INVOLVEMENT IN CLCD.
RX PubMed=9182765; DOI=10.1016/s0092-8674(00)80260-3;
RA Mundlos S., Otto F., Mundlos C., Mulliken J.B., Aylsworth A.S.,
RA Albright S., Lindhout D., Cole W.G., Henn W., Knoll J.H.M., Owen M.J.,
RA Mertelsmann R., Zabel B.U., Olsen B.R.;
RT "Mutations involving the transcription factor CBFA1 cause cleidocranial
RT dysplasia.";
RL Cell 89:773-779(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1 AND
RP 3).
RX PubMed=9434946; DOI=10.1007/s003359900679;
RA Geoffroy V., Corral D.A., Zhou L., Lee B., Karsenty G.;
RT "Genomic organization, expression of the human CBFA1 gene, and evidence for
RT an alternative splicing event affecting protein function.";
RL Mamm. Genome 9:54-57(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-19 (ISOFORM 1).
RX PubMed=9651525; DOI=10.1016/s0378-1119(98)00227-3;
RA Xiao Z.S., Thomas R., Hinson T.K., Quarles L.D.;
RT "Genomic structure and isoform expression of the mouse, rat and human
RT Cbfa1/Osf2 transcription factor.";
RL Gene 214:187-197(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 60-521 (ISOFORM 3).
RX PubMed=9233771; DOI=10.1038/sj.onc.1201352;
RA Zhang Y.-W., Bae S.-C., Takahashi E., Ito Y.;
RT "The cDNA cloning of the transcripts of human PEBP2alphaA/CBFA1 mapped to
RT 6p12.3-p21.1, the locus for cleidocranial dysplasia.";
RL Oncogene 15:367-371(1997).
RN [6]
RP INTERACTION WITH XRCC5 AND XRCC6.
RC TISSUE=Osteoblast;
RX PubMed=12145306; DOI=10.1074/jbc.m206482200;
RA Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S., Ornitz D.M.,
RA Towler D.A.;
RT "Regulation of osteocalcin gene expression by a novel Ku antigen
RT transcription factor complex.";
RL J. Biol. Chem. 277:37280-37291(2002).
RN [7]
RP INTERACTION WITH KAT6A AND KAT6B, AND FUNCTION.
RX PubMed=11965546; DOI=10.1038/sj.onc.1205367;
RA Pelletier N., Champagne N., Stifani S., Yang X.-J.;
RT "MOZ and MORF histone acetyltransferases interact with the Runt-domain
RT transcription factor Runx2.";
RL Oncogene 21:2729-2740(2002).
RN [8]
RP INTERACTION WITH CCNB1, PHOSPHORYLATION AT SER-451 BY CDK1, AND MUTAGENESIS
RP OF SER-451.
RX PubMed=16407259; DOI=10.1074/jbc.m508162200;
RA Qiao M., Shapiro P., Fosbrink M., Rus H., Kumar R., Passaniti A.;
RT "Cell cycle-dependent phosphorylation of the RUNX2 transcription factor by
RT cdc2 regulates endothelial cell proliferation.";
RL J. Biol. Chem. 281:7118-7128(2006).
RN [9]
RP INTERACTION WITH FOXP3.
RX PubMed=17377532; DOI=10.1038/nature05673;
RA Ono M., Yaguchi H., Ohkura N., Kitabayashi I., Nagamura Y., Nomura T.,
RA Miyachi Y., Tsukada T., Sakaguchi S.;
RT "Foxp3 controls regulatory T-cell function by interacting with
RT AML1/Runx1.";
RL Nature 446:685-689(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340 (ISOFORM 3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [11]
RP INVOLVEMENT IN MDMHB.
RX PubMed=23290074; DOI=10.1016/j.ajhg.2012.12.001;
RG FORGE Canada Consortium;
RA Moffatt P., Ben Amor M., Glorieux F.H., Roschger P., Klaushofer K.,
RA Schwartzentruber J.A., Paterson A.D., Hu P., Marshall C., Fahiminiya S.,
RA Majewski J., Beaulieu C.L., Boycott K.M., Rauch F.;
RT "Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly is
RT caused by a duplication in RUNX2.";
RL Am. J. Hum. Genet. 92:252-258(2013).
RN [12]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-238, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [13]
RP VARIANTS CLCD ARG-175 AND ASN-191.
RX PubMed=9207800; DOI=10.1038/ng0797-307;
RA Lee B., Thirunavukkarasu K., Zhou L., Pastore L., Baldini A., Hecht J.,
RA Geoffroy V., Ducy P., Karsenty G.;
RT "Missense mutations abolishing DNA binding of the osteoblast-specific
RT transcription factor OSF2/CBFA1 in cleidocranial dysplasia.";
RL Nat. Genet. 16:307-310(1997).
RN [14]
RP VARIANTS CLCD ARG-113; ARG-118; CYS-121; ARG-123; ARG-205; GLN-225 AND
RP TRP-225, AND VARIANT SER-511.
RX PubMed=10521292; DOI=10.1086/302622;
RA Quack I., Vonderstrass B., Stock M., Aylsworth A.S., Becker A., Brueton L.,
RA Lee P.J., Majewski F., Mulliken J.B., Suri M., Zenker M., Mundlos S.,
RA Otto F.;
RT "Mutation analysis of core binding factor A1 in patients with cleidocranial
RT dysplasia.";
RL Am. J. Hum. Genet. 65:1268-1278(1999).
RN [15]
RP VARIANTS CLCD ASN-133 DEL; GLN-169; ARG-175; GLN-190; ASN-191; CYS-193;
RP PHE-199; ALA-200; ARG-209 AND GLN-225.
RX PubMed=10545612; DOI=10.1093/hmg/8.12.2311;
RA Zhou G., Chen Y., Zhou L., Thirunavukkarasu K., Hecht J., Chitayat D.,
RA Gelb B.D., Pirinen S., Berry S.A., Greenberg C.R., Karsenty G., Lee B.;
RT "CBFA1 mutation analysis and functional correlation with phenotypic
RT variability in cleidocranial dysplasia.";
RL Hum. Mol. Genet. 8:2311-2316(1999).
RN [16]
RP VARIANT CLCD SER-197.
RX PubMed=10689183; DOI=10.1016/s0378-1119(99)00558-2;
RA Zhang Y.-W., Yasui N., Kakazu N., Abe T., Takada K., Imai S., Sato M.,
RA Nomura S., Ochi T., Okuzumi S., Nogami H., Nagai T., Ohashi H., Ito Y.;
RT "PEBP2alphaA/CBFA1 mutations in Japanese cleidocranial dysplasia
RT patients.";
RL Gene 244:21-28(2000).
RN [17]
RP VARIANT CLCD TRP-190.
RX PubMed=10980549;
RX DOI=10.1002/1098-1004(200009)16:3<277::aid-humu25>3.0.co;2-v;
RA Giannotti A., Tessa A., Patrono C., De Florio L., Velardo M.,
RA Dionisi-Vici C., Bertini E., Santorelli F.M.;
RT "A novel CBFA1 mutation (R190W) in an Italian family with cleidocranial
RT dysplasia.";
RL Hum. Mutat. 16:277-277(2000).
RN [18]
RP VARIANTS CLCD TRP-190; SER-197; ASN-218; ILE-220; TRP-225 AND GLN-225, AND
RP CHARACTERIZATION OF VARIANTS CLCD TRP-190; SER-197; ASN-218; ILE-220;
RP TRP-225 AND GLN-225.
RX PubMed=12196916; DOI=10.1086/342717;
RA Yoshida T., Kanegane H., Osato M., Yanagida M., Miyawaki T., Ito Y.,
RA Shigesada K.;
RT "Functional analysis of RUNX2 mutations in Japanese patients with
RT cleidocranial dysplasia demonstrates novel genotype-phenotype
RT correlations.";
RL Am. J. Hum. Genet. 71:724-738(2002).
RN [19]
RP VARIANT CLCD LEU-53.
RX PubMed=12081718; DOI=10.1034/j.1399-0004.2002.610505.x;
RA Machuca-Tzili L., Monroy-Jaramillo N., Gonzalez-del Angel A.,
RA Kofman-Alfaro S.;
RT "New mutations in the CBFA1 gene in two Mexican patients with cleidocranial
RT dysplasia.";
RL Clin. Genet. 61:349-353(2002).
RN [20]
RP VARIANT CLCD PRO-169.
RX PubMed=12424590; DOI=10.1007/s00431-002-0977-x;
RA Morava E., Karteszi J., Weisenbach J., Caliebe A., Mundlos S., Mehes K.;
RT "Cleidocranial dysplasia with decreased bone density and biochemical
RT findings of hypophosphatasia.";
RL Eur. J. Pediatr. 161:619-622(2002).
RN [21]
RP VARIANTS CLCD GLY-156; PRO-169; TRP-190; LYS-201; TRP-225; GLN-225 AND
RP VAL-362.
RX PubMed=11857736; DOI=10.1002/humu.10043;
RA Otto F., Kanegane H., Mundlos S.;
RT "Mutations in the RUNX2 gene in patients with cleidocranial dysplasia.";
RL Hum. Mutat. 19:209-216(2002).
RN [22]
RP VARIANTS CLCD GLY-131 AND GLN-225.
RX PubMed=16270353; DOI=10.1002/jcp.20552;
RA Kim H.-J., Nam S.-H., Kim H.-J., Park H.-S., Ryoo H.-M., Kim S.-Y.,
RA Cho T.-J., Kim S.-G., Bae S.-C., Kim I.-S., Stein J.L., van Wijnen A.J.,
RA Stein G.S., Lian J.B., Choi J.-Y.;
RT "Four novel RUNX2 mutations including a splice donor site result in the
RT cleidocranial dysplasia phenotype.";
RL J. Cell. Physiol. 207:114-122(2006).
RN [23]
RP VARIANT CLCD ILE-420.
RX PubMed=20082269; DOI=10.4238/vol9-1gmr685;
RA Wang G.X., Sun R.P., Song F.L.;
RT "A novel RUNX2 mutation (T420I) in Chinese patients with cleidocranial
RT dysplasia.";
RL Genet. Mol. Res. 9:41-47(2010).
RN [24]
RP VARIANTS CLCD ASN-118; SER-131; CYS-131; PRO-136; ASP-156; VAL-175;
RP LYS-175; SER-187; GLN-193; ILE-200; HIS-209; PRO-211; GLN-218; GLU-218;
RP LEU-225; GLY-228; ARG-233; ASN-287 AND ASN-420.
RX PubMed=20648631; DOI=10.1002/humu.21298;
RA Ott C.E., Leschik G., Trotier F., Brueton L., Brunner H.G., Brussel W.,
RA Guillen-Navarro E., Haase C., Kohlhase J., Kotzot D., Lane A.,
RA Lee-Kirsch M.A., Morlot S., Simon M.E.H., Steichen-Gersdorf E., Tegay D.H.,
RA Peters H., Mundlos S., Klopocki E.;
RT "Deletions of the RUNX2 gene are present in about 10% of individuals with
RT cleidocranial dysplasia.";
RL Hum. Mutat. 31:E1587-E1593(2010).
RN [25]
RP VARIANT CLCD TRP-225.
RX PubMed=19744171; DOI=10.1111/j.1601-0825.2009.01623.x;
RA Ryoo H.M., Kang H.Y., Lee S.K., Lee K.E., Kim J.W.;
RT "RUNX2 mutations in cleidocranial dysplasia patients.";
RL Oral Dis. 16:55-60(2010).
RN [26]
RP VARIANT CLCD CYS-131.
RX PubMed=24984680;
RA Callea M., Bellacchio E., Di Stazio M., Fattori F., Bertini E., Yavuz I.,
RA Clarich G., Gunay A.;
RT "A case of cleidocranial dysplasia with peculiar dental features:
RT pathogenetic role of the RUNX2 mutation and long term follow-up.";
RL Oral Health Dent. Manag. 13:548-551(2014).
RN [27]
RP VARIANTS CLCD ARG-175; GLN-190; GLN-225 AND 462-GLY--TYR-521 DEL,
RP CHARACTERIZATION OF VARIANT CLCD 462-GLY--TYR-521 DEL, AND FUNCTION.
RX PubMed=28703881; DOI=10.1002/jcb.26283;
RA Jung Y.J., Bae H.S., Ryoo H.M., Baek S.H.;
RT "A novel RUNX2 mutation in exon 8, G462X, in a patient with Cleidocranial
RT Dysplasia.";
RL J. Cell. Biochem. 119:1152-1162(2018).
RN [28]
RP VARIANTS CLCD GLY-193 AND 400-TYR--TYR-521 DEL, CHARACTERIZATION OF
RP VARIANTS CLCD GLY-193 AND 400-TYR--TYR-521 DEL, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=28505335; DOI=10.1093/mutage/gex012;
RA Zeng L., Wei J., Han D., Liu H., Liu Y., Zhao N., Sun S., Wang Y., Feng H.;
RT "Functional analysis of novel RUNX2 mutations in cleidocranial dysplasia.";
RL Mutagenesis 32:437-443(2017).
RN [29]
RP VARIANTS CLCD 67-GLN--TYR-521 DEL; ARG-113; THR-186 AND TRP-225,
RP CHARACTERIZATION OF VARIANTS CLCD 67-GLN--TYR-521 DEL; ARG-113; THR-186 AND
RP TRP-225, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=28738062; DOI=10.1371/journal.pone.0181653;
RA Zhang X., Liu Y., Wang X., Sun X., Zhang C., Zheng S.;
RT "Analysis of novel RUNX2 mutations in Chinese patients with cleidocranial
RT dysplasia.";
RL PLoS ONE 12:E0181653-E0181653(2017).
CC -!- FUNCTION: Transcription factor involved in osteoblastic differentiation
CC and skeletal morphogenesis (PubMed:28505335, PubMed:28738062,
CC PubMed:28703881). Essential for the maturation of osteoblasts and both
CC intramembranous and endochondral ossification. CBF binds to the core
CC site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including
CC murine leukemia virus, polyomavirus enhancer, T-cell receptor
CC enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I)
CC collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports
CC transcription activation: synergizes with SPEN/MINT to enhance FGFR2-
CC mediated activation of the osteocalcin FGF-responsive element (OCFRE)
CC (By similarity). Inhibits KAT6B-dependent transcriptional activation.
CC {ECO:0000250, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:28505335,
CC ECO:0000269|PubMed:28703881, ECO:0000269|PubMed:28738062}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha subunit
CC binds DNA as a monomer and through the Runt domain. DNA-binding is
CC increased by heterodimerization. Interacts with XRCC6 (Ku70) and XRCC5
CC (Ku80). Interacts with HIVEP3. Interacts with IFI204. Interaction with
CC SATB2; the interaction results in enhanced DNA binding and
CC transactivation by these transcription factors. Binds to HIPK3.
CC Interacts (isoform 3) with DDX5. Interacts with FOXO1 (via a C-terminal
CC region); the interaction inhibits RUNX2 transcriptional activity
CC towards BGLAP. This interaction is prevented on insulin or IGF1
CC stimulation as FOXO1 is exported from the nucleus (By similarity).
CC Interacts with CCNB1, KAT6A and KAT6B. Interacts with FOXP3. Interacts
CC with TMEM119 (By similarity). Interacts with OLFM2 (By similarity).
CC {ECO:0000250|UniProtKB:Q08775, ECO:0000250|UniProtKB:Q9Z2J9,
CC ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:12145306,
CC ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:17377532}.
CC -!- INTERACTION:
CC Q13950; Q13526: PIN1; NbExp=7; IntAct=EBI-976402, EBI-714158;
CC Q13950; O15297: PPM1D; NbExp=4; IntAct=EBI-976402, EBI-1551512;
CC Q13950; O43541: SMAD6; NbExp=3; IntAct=EBI-976402, EBI-976374;
CC Q13950; O15350: TP73; NbExp=3; IntAct=EBI-976402, EBI-389606;
CC Q13950; P17480: UBTF; NbExp=4; IntAct=EBI-976402, EBI-396235;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28505335,
CC ECO:0000269|PubMed:28738062}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Cbfa1a;
CC IsoId=Q13950-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13950-2; Sequence=VSP_005937;
CC Name=3; Synonyms=Cbfa1b;
CC IsoId=Q13950-3; Sequence=VSP_005938;
CC -!- TISSUE SPECIFICITY: Specifically expressed in osteoblasts.
CC -!- DOMAIN: A proline/serine/threonine rich region at the C-terminus is
CC necessary for transcriptional activation of target genes and contains
CC the phosphorylation sites.
CC -!- PTM: Phosphorylated; probably by MAP kinases (MAPK). Phosphorylation by
CC HIPK3 is required for the SPEN/MINT and FGF2 transactivation during
CC osteoblastic differentiation (By similarity). Phosphorylation at Ser-
CC 451 by CDK1 promotes endothelial cell proliferation required for tumor
CC angiogenesis probably by facilitating cell cycle progression. Isoform 3
CC is phosphorylated on Ser-340. {ECO:0000250,
CC ECO:0000269|PubMed:16407259}.
CC -!- DISEASE: Cleidocranial dysplasia (CLCD) [MIM:119600]: Autosomal
CC dominant skeletal disorder with high penetrance and variable
CC expressivity. It is due to defective endochondral and intramembranous
CC bone formation. Typical features include hypoplasia/aplasia of
CC clavicles, patent fontanelles, wormian bones (additional cranial plates
CC caused by abnormal ossification of the calvaria), supernumerary teeth,
CC short stature, and other skeletal changes. In some cases defects in
CC RUNX2 are exclusively associated with dental anomalies.
CC {ECO:0000269|PubMed:10521292, ECO:0000269|PubMed:10545612,
CC ECO:0000269|PubMed:10689183, ECO:0000269|PubMed:10980549,
CC ECO:0000269|PubMed:11857736, ECO:0000269|PubMed:12081718,
CC ECO:0000269|PubMed:12196916, ECO:0000269|PubMed:12424590,
CC ECO:0000269|PubMed:16270353, ECO:0000269|PubMed:19744171,
CC ECO:0000269|PubMed:20082269, ECO:0000269|PubMed:20648631,
CC ECO:0000269|PubMed:24984680, ECO:0000269|PubMed:28505335,
CC ECO:0000269|PubMed:28703881, ECO:0000269|PubMed:28738062,
CC ECO:0000269|PubMed:9182765, ECO:0000269|PubMed:9207800}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Metaphyseal dysplasia with maxillary hypoplasia with or
CC without brachydactyly (MDMHB) [MIM:156510]: An autosomal dominant bone
CC dysplasia characterized by metaphyseal flaring of long bones,
CC enlargement of the medial halves of the clavicles, maxillary
CC hypoplasia, variable brachydactyly, and dystrophic teeth.
CC {ECO:0000269|PubMed:23290074}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. Analysis for copy-number
CC variations revealed that a 105 kb duplication within RUNX2 segregated
CC with the MDMHB phenotype in a region with maximum linkage. Real-time
CC PCR for copy-number variation in genomic DNA in eight samples, as well
CC as sequence analysis of fibroblast cDNA from one subject with MDMHB
CC confirmed that affected family members were heterozygous for the
CC presence of an intragenic duplication encompassing exons 3 to 5 of
CC RUNX2. These three exons code for the Q/A domain and the functionally
CC essential DNA-binding Runt domain of RUNX2. The RUNX2 duplication found
CC in individuals with MDMHB leads to a gain of function
CC (PubMed:23290074). {ECO:0000269|PubMed:23290074}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RUNX2ID42183ch6p21.html";
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DR EMBL; AF001450; AAB65159.2; -; Genomic_DNA.
DR EMBL; AF001443; AAB65159.2; JOINED; Genomic_DNA.
DR EMBL; AF001444; AAB65159.2; JOINED; Genomic_DNA.
DR EMBL; AF001445; AAB65159.2; JOINED; Genomic_DNA.
DR EMBL; AF001446; AAB65159.2; JOINED; Genomic_DNA.
DR EMBL; AF001447; AAB65159.2; JOINED; Genomic_DNA.
DR EMBL; AF001448; AAB65159.2; JOINED; Genomic_DNA.
DR EMBL; AF001449; AAB65159.2; JOINED; Genomic_DNA.
DR EMBL; AF001450; AAB65158.1; -; Genomic_DNA.
DR EMBL; AF001444; AAB65158.1; JOINED; Genomic_DNA.
DR EMBL; AF001445; AAB65158.1; JOINED; Genomic_DNA.
DR EMBL; AF001446; AAB65158.1; JOINED; Genomic_DNA.
DR EMBL; AF001447; AAB65158.1; JOINED; Genomic_DNA.
DR EMBL; AF001448; AAB65158.1; JOINED; Genomic_DNA.
DR EMBL; AF001449; AAB65158.1; JOINED; Genomic_DNA.
DR EMBL; AL161907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL358135; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL096865; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF053952; AAC78624.1; -; mRNA.
DR EMBL; AF053949; AAC77441.1; -; Genomic_DNA.
DR EMBL; L40992; AAA89072.1; -; mRNA.
DR CCDS; CCDS43467.2; -. [Q13950-1]
DR CCDS; CCDS43468.2; -. [Q13950-3]
DR RefSeq; NP_001015051.3; NM_001015051.3. [Q13950-3]
DR RefSeq; NP_001019801.3; NM_001024630.3. [Q13950-1]
DR PDB; 6VG8; X-ray; 4.31 A; D=111-233.
DR PDB; 6VGD; X-ray; 4.20 A; D=111-287.
DR PDB; 6VGE; X-ray; 4.25 A; D=111-287.
DR PDB; 6VGG; X-ray; 4.31 A; D=111-287.
DR PDBsum; 6VG8; -.
DR PDBsum; 6VGD; -.
DR PDBsum; 6VGE; -.
DR PDBsum; 6VGG; -.
DR AlphaFoldDB; Q13950; -.
DR BMRB; Q13950; -.
DR SMR; Q13950; -.
DR BioGRID; 107308; 71.
DR CORUM; Q13950; -.
DR DIP; DIP-36707N; -.
DR ELM; Q13950; -.
DR IntAct; Q13950; 24.
DR MINT; Q13950; -.
DR STRING; 9606.ENSP00000360493; -.
DR GlyGen; Q13950; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q13950; -.
DR PhosphoSitePlus; Q13950; -.
DR SwissPalm; Q13950; -.
DR BioMuta; RUNX2; -.
DR DMDM; 17368460; -.
DR EPD; Q13950; -.
DR jPOST; Q13950; -.
DR MassIVE; Q13950; -.
DR MaxQB; Q13950; -.
DR PaxDb; Q13950; -.
DR PeptideAtlas; Q13950; -.
DR PRIDE; Q13950; -.
DR ProteomicsDB; 59767; -. [Q13950-1]
DR ProteomicsDB; 59768; -. [Q13950-2]
DR ProteomicsDB; 59769; -. [Q13950-3]
DR Antibodypedia; 3645; 911 antibodies from 45 providers.
DR DNASU; 860; -.
DR Ensembl; ENST00000359524.7; ENSP00000352514.5; ENSG00000124813.23. [Q13950-2]
DR Ensembl; ENST00000371432.7; ENSP00000360486.4; ENSG00000124813.23. [Q13950-3]
DR Ensembl; ENST00000371436.10; ENSP00000360491.6; ENSG00000124813.23. [Q13950-3]
DR Ensembl; ENST00000371438.5; ENSP00000360493.1; ENSG00000124813.23. [Q13950-1]
DR Ensembl; ENST00000647337.2; ENSP00000495497.1; ENSG00000124813.23. [Q13950-1]
DR GeneID; 860; -.
DR KEGG; hsa:860; -.
DR MANE-Select; ENST00000647337.2; ENSP00000495497.1; NM_001024630.4; NP_001019801.3.
DR UCSC; uc003oxt.5; human. [Q13950-1]
DR CTD; 860; -.
DR DisGeNET; 860; -.
DR GeneCards; RUNX2; -.
DR GeneReviews; RUNX2; -.
DR HGNC; HGNC:10472; RUNX2.
DR HPA; ENSG00000124813; Low tissue specificity.
DR MalaCards; RUNX2; -.
DR MIM; 119600; phenotype.
DR MIM; 156510; phenotype.
DR MIM; 600211; gene.
DR neXtProt; NX_Q13950; -.
DR OpenTargets; ENSG00000124813; -.
DR Orphanet; 1452; Cleidocranial dysplasia.
DR Orphanet; 2504; Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome.
DR PharmGKB; PA34885; -.
DR VEuPathDB; HostDB:ENSG00000124813; -.
DR eggNOG; KOG3982; Eukaryota.
DR GeneTree; ENSGT00940000160171; -.
DR InParanoid; Q13950; -.
DR OMA; XVVALGE; -.
DR OrthoDB; 562214at2759; -.
DR PhylomeDB; Q13950; -.
DR TreeFam; TF321496; -.
DR PathwayCommons; Q13950; -.
DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2.
DR Reactome; R-HSA-8939246; RUNX1 regulates transcription of genes involved in differentiation of myeloid cells.
DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation.
DR Reactome; R-HSA-8941284; RUNX2 regulates chondrocyte maturation.
DR Reactome; R-HSA-8941326; RUNX2 regulates bone development.
DR Reactome; R-HSA-8941332; RUNX2 regulates genes involved in cell migration.
DR Reactome; R-HSA-8941333; RUNX2 regulates genes involved in differentiation of myeloid cells.
DR SignaLink; Q13950; -.
DR SIGNOR; Q13950; -.
DR BioGRID-ORCS; 860; 51 hits in 1097 CRISPR screens.
DR ChiTaRS; RUNX2; human.
DR GeneWiki; RUNX2; -.
DR GenomeRNAi; 860; -.
DR Pharos; Q13950; Tbio.
DR PRO; PR:Q13950; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q13950; protein.
DR Bgee; ENSG00000124813; Expressed in tibia and 162 other tissues.
DR ExpressionAtlas; Q13950; baseline and differential.
DR Genevisible; Q13950; HS.
DR GO; GO:0000785; C:chromatin; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0043425; F:bHLH transcription factor binding; IEA:Ensembl.
DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:BHF-UCL.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISS:BHF-UCL.
DR GO; GO:0002063; P:chondrocyte development; IEA:Ensembl.
DR GO; GO:0002062; P:chondrocyte differentiation; IBA:GO_Central.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IBA:GO_Central.
DR GO; GO:0036076; P:ligamentous ossification; IEA:Ensembl.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IBA:GO_Central.
DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:UniProtKB.
DR GO; GO:0002051; P:osteoblast fate commitment; IEA:Ensembl.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; ISS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; IBA:GO_Central.
DR GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0033591; P:response to L-ascorbic acid; IEA:Ensembl.
DR GO; GO:1904383; P:response to sodium phosphate; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
DR Gene3D; 2.60.40.720; -; 1.
DR Gene3D; 4.10.770.10; -; 1.
DR InterPro; IPR000040; AML1_Runt.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR012346; p53/RUNT-type_TF_DNA-bd_sf.
DR InterPro; IPR013524; Runt_dom.
DR InterPro; IPR027384; Runx_central_dom_sf.
DR InterPro; IPR013711; RunxI_C_dom.
DR InterPro; IPR016554; TF_Runt-rel_RUNX.
DR PANTHER; PTHR11950; PTHR11950; 1.
DR Pfam; PF00853; Runt; 1.
DR Pfam; PF08504; RunxI; 1.
DR PIRSF; PIRSF009374; TF_Runt-rel_RUNX; 1.
DR PRINTS; PR00967; ONCOGENEAML1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS51062; RUNT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Differentiation; Disease variant;
KW DNA-binding; Isopeptide bond; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..521
FT /note="Runt-related transcription factor 2"
FT /id="PRO_0000174659"
FT DOMAIN 101..229
FT /note="Runt"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT REGION 18..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 242..258
FT /note="Required for interaction with FOXO1"
FT /evidence="ECO:0000250"
FT REGION 336..439
FT /note="Interaction with KAT6A"
FT /evidence="ECO:0000250"
FT REGION 374..468
FT /note="Interaction with KAT6B"
FT /evidence="ECO:0000269|PubMed:11965546"
FT REGION 460..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..242
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..273
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..329
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 469..512
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 267
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q08775"
FT MOD_RES 451
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:16407259"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..19
FT /note="MASNSLFSTVTPCQQNFFW -> MRIPV (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005937"
FT VAR_SEQ 341..362
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9233771"
FT /id="VSP_005938"
FT VARIANT 53
FT /note="Q -> L (in CLCD)"
FT /evidence="ECO:0000269|PubMed:12081718"
FT /id="VAR_064081"
FT VARIANT 67..521
FT /note="Missing (in CLCD; decreased subcellular localization
FT in the nucleus; decreased transactivation activity)"
FT /evidence="ECO:0000269|PubMed:28738062"
FT /id="VAR_079576"
FT VARIANT 78..83
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:9182765"
FT /id="VAR_012131"
FT VARIANT 84
FT /note="A -> AAAAAAAAAAA (in CLCD; the patient also shows
FT brachydactyly of hands and feet)"
FT /evidence="ECO:0000269|PubMed:9182765"
FT /id="VAR_012130"
FT VARIANT 113
FT /note="L -> R (in CLCD; unchanged subcellular localization;
FT decreased transactivation activity)"
FT /evidence="ECO:0000269|PubMed:10521292,
FT ECO:0000269|PubMed:28738062"
FT /id="VAR_012132"
FT VARIANT 118
FT /note="S -> N (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064082"
FT VARIANT 118
FT /note="S -> R (in CLCD)"
FT /evidence="ECO:0000269|PubMed:10521292"
FT /id="VAR_012133"
FT VARIANT 121
FT /note="F -> C (in CLCD)"
FT /evidence="ECO:0000269|PubMed:10521292"
FT /id="VAR_012134"
FT VARIANT 123
FT /note="C -> R (in CLCD)"
FT /evidence="ECO:0000269|PubMed:10521292"
FT /id="VAR_012135"
FT VARIANT 131
FT /note="R -> C (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631,
FT ECO:0000269|PubMed:24984680"
FT /id="VAR_064083"
FT VARIANT 131
FT /note="R -> G (in CLCD)"
FT /evidence="ECO:0000269|PubMed:16270353"
FT /id="VAR_064084"
FT VARIANT 131
FT /note="R -> S (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064085"
FT VARIANT 133
FT /note="Missing (in CLCD)"
FT /evidence="ECO:0000269|PubMed:10545612"
FT /id="VAR_012136"
FT VARIANT 136
FT /note="L -> P (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064086"
FT VARIANT 156
FT /note="V -> D (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064087"
FT VARIANT 156
FT /note="V -> G (in CLCD)"
FT /evidence="ECO:0000269|PubMed:11857736"
FT /id="VAR_064088"
FT VARIANT 169
FT /note="R -> P (in CLCD; dbSNP:rs104893995)"
FT /evidence="ECO:0000269|PubMed:11857736,
FT ECO:0000269|PubMed:12424590"
FT /id="VAR_064089"
FT VARIANT 169
FT /note="R -> Q (in CLCD; dbSNP:rs104893995)"
FT /evidence="ECO:0000269|PubMed:10545612"
FT /id="VAR_012137"
FT VARIANT 175
FT /note="M -> K (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064090"
FT VARIANT 175
FT /note="M -> R (in CLCD; abolishes DNA binding;
FT dbSNP:rs104893989)"
FT /evidence="ECO:0000269|PubMed:10545612,
FT ECO:0000269|PubMed:28703881, ECO:0000269|PubMed:9207800"
FT /id="VAR_012138"
FT VARIANT 175
FT /note="M -> V (in CLCD; dbSNP:rs201647225)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064091"
FT VARIANT 186
FT /note="R -> T (in CLCD; unchanged subcellular localization;
FT decreased transactivation activity)"
FT /evidence="ECO:0000269|PubMed:28738062"
FT /id="VAR_079577"
FT VARIANT 187
FT /note="F -> S (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064092"
FT VARIANT 190
FT /note="R -> Q (in CLCD; abolishes DNA binding;
FT dbSNP:rs1057521068)"
FT /evidence="ECO:0000269|PubMed:10545612,
FT ECO:0000269|PubMed:28703881"
FT /id="VAR_012139"
FT VARIANT 190
FT /note="R -> W (in CLCD; has severely impaired DNA binding
FT and transactivation)"
FT /evidence="ECO:0000269|PubMed:10980549,
FT ECO:0000269|PubMed:11857736, ECO:0000269|PubMed:12196916"
FT /id="VAR_012140"
FT VARIANT 191
FT /note="S -> N (in CLCD; abolishes DNA binding;
FT dbSNP:rs104893990)"
FT /evidence="ECO:0000269|PubMed:10545612,
FT ECO:0000269|PubMed:9207800"
FT /id="VAR_012141"
FT VARIANT 193
FT /note="R -> C (in CLCD)"
FT /evidence="ECO:0000269|PubMed:10545612"
FT /id="VAR_012142"
FT VARIANT 193
FT /note="R -> G (in CLCD; unchanged subcellular localization;
FT decreased transactivation activity)"
FT /evidence="ECO:0000269|PubMed:28505335"
FT /id="VAR_079578"
FT VARIANT 193
FT /note="R -> Q (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064093"
FT VARIANT 197
FT /note="F -> S (in CLCD; retains heterodimerization activity
FT together with a trace potential for DNA binding; retains a
FT low but still substantial transactivation activity)"
FT /evidence="ECO:0000269|PubMed:10689183,
FT ECO:0000269|PubMed:12196916"
FT /id="VAR_012143"
FT VARIANT 199
FT /note="L -> F (in CLCD; abolishes DNA binding)"
FT /evidence="ECO:0000269|PubMed:10545612"
FT /id="VAR_012144"
FT VARIANT 200
FT /note="T -> A (in CLCD; mild; associated also with isolated
FT dental anomalies; normal DNA binding; dbSNP:rs104893993)"
FT /evidence="ECO:0000269|PubMed:10545612"
FT /id="VAR_012145"
FT VARIANT 200
FT /note="T -> I (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064094"
FT VARIANT 201
FT /note="I -> K (in CLCD)"
FT /evidence="ECO:0000269|PubMed:11857736"
FT /id="VAR_064095"
FT VARIANT 205
FT /note="T -> R (in CLCD)"
FT /evidence="ECO:0000269|PubMed:10521292"
FT /id="VAR_012146"
FT VARIANT 209
FT /note="Q -> H (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064096"
FT VARIANT 209
FT /note="Q -> R (in CLCD)"
FT /evidence="ECO:0000269|PubMed:10545612"
FT /id="VAR_012147"
FT VARIANT 211
FT /note="A -> P (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064097"
FT VARIANT 218
FT /note="K -> E (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064098"
FT VARIANT 218
FT /note="K -> N (in CLCD; has severely impaired DNA binding
FT and transactivation; dbSNP:rs752933596)"
FT /evidence="ECO:0000269|PubMed:12196916"
FT /id="VAR_064099"
FT VARIANT 218
FT /note="K -> Q (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064100"
FT VARIANT 220
FT /note="T -> I (in CLCD; has severely impaired DNA binding
FT and transactivation)"
FT /evidence="ECO:0000269|PubMed:12196916"
FT /id="VAR_064101"
FT VARIANT 225
FT /note="R -> L (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064102"
FT VARIANT 225
FT /note="R -> Q (in CLCD; interferes with nuclear
FT localization; abolishes DNA binding; dbSNP:rs104893991)"
FT /evidence="ECO:0000269|PubMed:10521292,
FT ECO:0000269|PubMed:10545612, ECO:0000269|PubMed:11857736,
FT ECO:0000269|PubMed:12196916, ECO:0000269|PubMed:16270353,
FT ECO:0000269|PubMed:28703881"
FT /id="VAR_012148"
FT VARIANT 225
FT /note="R -> W (in CLCD; interferes with nuclear
FT localization; has severely impaired DNA binding and
FT transactivation; dbSNP:rs104893992)"
FT /evidence="ECO:0000269|PubMed:10521292,
FT ECO:0000269|PubMed:11857736, ECO:0000269|PubMed:12196916,
FT ECO:0000269|PubMed:19744171, ECO:0000269|PubMed:28738062"
FT /id="VAR_012149"
FT VARIANT 228
FT /note="R -> G (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064103"
FT VARIANT 233
FT /note="K -> R (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064104"
FT VARIANT 287
FT /note="D -> N (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064105"
FT VARIANT 362
FT /note="A -> V (in CLCD)"
FT /evidence="ECO:0000269|PubMed:11857736"
FT /id="VAR_064106"
FT VARIANT 400..521
FT /note="Missing (in CLCD; unchanged subcellular
FT localization; decreased transactivation activity)"
FT /evidence="ECO:0000269|PubMed:28505335"
FT /id="VAR_079579"
FT VARIANT 420
FT /note="T -> I (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20082269"
FT /id="VAR_064107"
FT VARIANT 420
FT /note="T -> N (in CLCD)"
FT /evidence="ECO:0000269|PubMed:20648631"
FT /id="VAR_064108"
FT VARIANT 462..521
FT /note="Missing (in CLCD; decreased protein stability;
FT decreased transactivation activity; decreased osteoblast
FT differentiation)"
FT /evidence="ECO:0000269|PubMed:28703881"
FT /id="VAR_079580"
FT VARIANT 511
FT /note="G -> S (in dbSNP:rs11498198)"
FT /evidence="ECO:0000269|PubMed:10521292"
FT /id="VAR_012150"
FT MUTAGEN 451
FT /note="S->A: Reduced DNA-binding and impaired
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:16407259"
FT CONFLICT 16
FT /note="N -> S (in Ref. 4; AAC77441)"
FT /evidence="ECO:0000305"
FT MOD_RES Q13950-3:340
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336"
SQ SEQUENCE 521 AA; 56648 MW; 44C4F3867D6F3EB1 CRC64;
MASNSLFSTV TPCQQNFFWD PSTSRRFSPP SSSLQPGKMS DVSPVVAAQQ QQQQQQQQQQ
QQQQQQQQQQ QEAAAAAAAA AAAAAAAAAV PRLRPPHDNR TMVEIIADHP AELVRTDSPN
FLCSVLPSHW RCNKTLPVAF KVVALGEVPD GTVVTVMAGN DENYSAELRN ASAVMKNQVA
RFNDLRFVGR SGRGKSFTLT ITVFTNPPQV ATYHRAIKVT VDGPREPRRH RQKLDDSKPS
LFSDRLSDLG RIPHPSMRVG VPPQNPRPSL NSAPSPFNPQ GQSQITDPRQ AQSSPPWSYD
QSYPSYLSQM TSPSIHSTTP LSSTRGTGLP AITDVPRRIS DDDTATSDFC LWPSTLSKKS
QAGASELGPF SDPRQFPSIS SLTESRFSNP RMHYPATFTY TPPVTSGMSL GMSATTHYHT
YLPPPYPGSS QSQSGPFQTS STPYLYYGTS SGSYQFPMVP GGDRSPSRML PPCTTTSNGS
TLLNPNLPNQ NDGVDADGSH SSSPTVLNSS GRMDESVWRP Y
