SHOX2

Chr 3

SHOX homeobox 2

Also known as: OG12, OG12X, SHOT

NCBI Gene: 6474 ENSG00000168779 UniProt: O60902

This gene is a member of the homeobox family of genes that encode proteins containing a 60-amino acid residue motif that represents a DNA binding domain. Homeobox genes have been characterized extensively as transcriptional regulators involved in pattern formation in both invertebrate and vertebrate species. Several human genetic disorders are caused by aberrations in human homeobox genes. This locus represents a pseudoautosomal homeobox gene that is thought to be responsible for idiopathic short stature, and it is implicated in the short stature phenotype of Turner syndrome patients. This gene is considered to be a candidate gene for Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

Research

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.83

Clinical Summary— SHOX2

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.016

Z-score 1.99

OE 0.40 (0.20–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.10Z-score

OE missense 1.02 (0.91–1.15)

196 obs / 192.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.40 (0.20–0.83)

0≤0.351.4

Missense OE?1.02 (0.91–1.15)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 5 / 12.7Missense obs/exp: 196 / 192.1Syn Z: -1.38

This gene — mechanism propensity

0.75top 25%

GOF

0.5562th %ile

LOF

0.54top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.