RUNX2

Chr 6

RUNX family transcription factor 2

Also known as: AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD, OSF-2, OSF2

NCBI Gene: 860ENSG00000124813UniProt: Q13950

This gene is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Two regions of potential trinucleotide repeat expansions are present in the N-terminal region of the encoded protein, and these and other mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD). Transcript variants that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing. [provided by RefSeq, Jul 2016]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCleidocranial dysplasia 1
UniProtMetaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
5
Active trials
1791
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.34
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — RUNX2
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.34LOEUF
pLI 0.949
Z-score 3.82
OE 0.13 (0.06–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.60Z-score
OE missense 0.74 (0.66–0.83)
225 obs / 303.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.13 (0.06–0.34)
0≤0.351.4
Missense OE?0.74 (0.66–0.83)
0≤0.61.4
Synonymous OE?1.21
0≤1.21.6
LoF obs/exp: 3 / 22.6Missense obs/exp: 225 / 303.6Syn Z: -1.88

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RUNX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients