Locus CCD RUNX2

A condition that primarily affects the development of the bones and teeth. Characteristic features include underdeveloped or absent collarbones (clavicles); dental abnormalities; and delayed closing of the spaces between the skull bones (fontanels). Other features may include decreased bone density (osteopenia), osteoporosis, hearing loss, bone abnormalities of the hands, and recurrent sinus and ear infections¹.

Prevalence

All conditions 1/1,000,000 births (likely underdiagnosed); Utah population frequency 0.12/10,000. Found in many ethnic groups². TR expansions causative in 2 individuals³.

Age of Onset

0 (birth)⁴.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr6:45390487-45390538

hg38 chr6:45422750-45422801

t2t chr6:45257567-45257618

Details

Benign range (4-17 repeats) established from gnomAD and primary literature; pathogenic ranges (20-27) reflect two clinical cases to date^5,6. Intermediate alleles (i.e, 18 repeats; 19 not reported) appear to not be associated with disease^7,6. The gene RUNX2 was previously called CBFA1, as reflected in some of the literature⁸.

Mechanism

LoF

Polyalanine expansion leading to haploinsufficiency⁶.

Detection

Year

Causation identified in 2015⁶; clinical association found in 1997⁸

Location in Gene

Coding Exon 3

Gene Strand

Alleles

Ref. Motif

GCN

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GCN

Pathogenic (gene)

CNG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0007340

Vérification de la connexion...

orphanet:1452

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

4genereviews:NBK1513

gnomAD

gnomad:RUNX2

Characterisation of novel RUNX2 mutation with alanine tract expansion from Japanese cleidocranial dysplasia patient.

Akio,Shibata, Junichiro,Machida, Seishi,Yamaguchi, Masashi,Kimura, Tadashi,Tatematsu, Hitoshi,Miyachi, Masaki,Matsushita, Hiroshi,Kitoh, Naoki,Ishiguro, Atsuo,Nakayama, Yujiro,Higashi, Kazuo,Shimozato, Yoshihito,Tokita

Mutagenesis · 2015-07-28

pmid:26220009

RUNX2 analysis of Danish cleidocranial dysplasia families.

L,Hansen, A K,Riis, A,Silahtaroglu, H,Hove, E,Lauridsen, H,Eiberg, S,Kreiborg

Clinical genetics · 2011-03-01

pmid:20560987

Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia.

S,Mundlos, F,Otto, C,Mundlos, J B,Mulliken, A S,Aylsworth, S,Albright, D,Lindhout, W G,Cole, W,Henn, J H,Knoll, M J,Owen, R,Mertelsmann, B U,Zabel, B R,Olsen

Cell · 1997-05-30

pmid:9182765

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Novel RUNX1/2 fusions in unclassified cystic squamous salivary gland tumors: Possible expansion of the keratocystoma family.

Justin A,Bishop, Masato,Nakaguro, Doreen,Palsgrove, Anna,Trzcinska, Anne C,McLean, Jeffrey,Gagan, Junji,Shibahara, Toshitaka,Nagao

Annals of diagnostic pathology · 2025-12-26

pmid:41468806

Reanalysis of Next-Generation Sequencing Data to Detect Tandem Repeat Expansions in 1,106 Czech Probands With Neurologic Disease.

Alena,Musilova, Petra,Lassuthova, Anna,Uhrova Meszarosova, Barbora,Straka, Jana,Krejcikova, Anna,Berounska, Marketa,Vlckova, Zuzana,Musova, Dana,Safka Brozkova

Neurology. Genetics · 2025-06-25

pmid:40585427

Effects of G-CSF on hPDLSC proliferation and osteogenic differentiation in the LPS-induced inflammatory microenvironment.

Hui,Yu, Pengcheng,Wang, Haibin,Lu, Jiurong,Guan, Fang,Yao, Tianyi,Zhang, Qiuxu,Wang, Zuomin,Wang

BMC oral health · 2023-06-26

pmid:37365568

Osmolarity modulates the de-differentiation of horse articular chondrocytes during cell expansion in vitro: implications for tissue engineering in cartilage repair.

Elena,De Angelis, Amelia,Barilli, Roberta,Saleri, Bianca Maria,Rotoli, Francesca,Ravanetti, Francesca,Ferrari, Luca,Ferrari, Paolo,Martelli, Valeria,Dall'Asta, Paolo,Borghetti

Veterinary research communications · 2023-05-19

pmid:37202645

Unblending of Transcriptional Condensates in Human Repeat Expansion Disease.

Shaon,Basu, Sebastian D,Mackowiak, Henri,Niskanen, Dora,Knezevic, Vahid,Asimi, Stefanie,Grosswendt, Hylkje,Geertsema, Salaheddine,Ali, Ivana,Jerković, Helge,Ewers, Stefan,Mundlos, Alexander,Meissner, Daniel M,Ibrahim, Denes,Hnisz

Cell · 2020-05-07

pmid:32386547

Association of polyalanine and polyglutamine coiled coils mediates expansion disease-related protein aggregation and dysfunction.

Ilaria,Pelassa, Davide,Corà, Federico,Cesano, Francisco J,Monje, Pier Giorgio,Montarolo, Ferdinando,Fiumara

Human molecular genetics · 2014-02-04

pmid:24497578

Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation.

Nigel A,Morrison, Alexandre A,Stephens, Motomi,Osato, Patsie,Polly, Timothy C,Tan, Namiko,Yamashita, James D,Doecke, Julie,Pasco, Nicolette,Fozzard, Graeme,Jones, Stuart H,Ralston, Philip N,Sambrook, Richard L,Prince, Geoff C,Nicholson

PloS one · 2012-08-13

pmid:22912713

Runx2 contributes to murine Col10a1 gene regulation through direct interaction with its cis-enhancer.

Feifei,Li, Yaojuan,Lu, Ming,Ding, Dobrawa,Napierala, Sam,Abbassi, Yuqing,Chen, Xiangyun,Duan, Siying,Wang, Brendan,Lee, Qiping,Zheng

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2011-12-01

pmid:21887706

The polycystic kidney disease 1 (Pkd1) gene is required for the responses of osteochondroprogenitor cells to midpalatal suture expansion in mice.

Bo,Hou, Elona,Kolpakova-Hart, Naomi,Fukai, Kimberly,Wu, Bjorn R,Olsen

Bone · 2009-03-02

pmid:19264154