Human Gene Module / Chromosome X,Y / SHOX

SHOXshort stature homeobox

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
7 / 0
Aliases
SHOX, GCFX,  PHOGY,  SS, SHOX
Associated Syndromes
-
Chromosome Band
Yp11.2
Associated Disorders
-
Relevance to Autism

Analysis of aCGH data from a discovery cohort of 90 adult ASD cases and a follow-up cohort of 26,574 patients, including 18,857 cases with NDD (3541 of those with ASD), demonstrated a statistically significant enrichment of SHOX microduplications in NDD cases (P=0.00036; OR=2.21), particularly in those with ASD (P=9.18E-07; OR=3.63), compared with 12,594 controls (Tropeano et al., 2016). A novel de novo predicted damaging missense variant in SHOX were observed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Molecular Function

This gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. Defects in this gene are associated with idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SHOX (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary Microduplications at the pseudoautosomal SHOX locus in autism spectrum disorders and related neurodevelopmental conditions Tropeano M , et al. (2016) Yes -
3 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain De novo - - 27073233 Tropeano M , et al. (2016)
- - copy_number_gain Unknown - - 27073233 Tropeano M , et al. (2016)
- - copy_number_gain Familial Maternal - 27073233 Tropeano M , et al. (2016)
- - copy_number_gain Familial Paternal - 27073233 Tropeano M , et al. (2016)
- - copy_number_gain Unknown Not maternal - 27073233 Tropeano M , et al. (2016)
c.518G>A p.Arg173His missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.728del p.Pro243ArgfsTer164 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Analysis of aCGH data from a discovery cohort of 90 adult ASD cases and a follow-up cohort of 26,574 patients, including 18,857 cases with NDD (3541 of those with ASD), demonstrated a statistically significant enrichment of SHOX microduplications in NDD cases (P=0.00036; OR=2.21), particularly in those with ASD (P=9.18E-07; OR=3.63), compared with 12,594 controls (Tropeano et al., 2016). However, relatively low calculated penetrance values for SHOX microduplications for ASD (3.6%, 95% CI 2.1%-6.1%) and NDDs (8.7%, 95% CI 5.8%-13.3%) were given in this report. A novel de novo predicted damaging missense variant in SHOX were observed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Analysis of aCGH data from a discovery cohort of 90 adult ASD cases and a follow-up cohort of 26,574 patients, including 18,857 cases with NDD (3541 of those with ASD), demonstrated a statistically significant enrichment of SHOX microduplications in NDD cases (P=0.00036; OR=2.21), particularly in those with ASD (P=9.18E-07; OR=3.63), compared with 12,594 controls (Tropeano et al., 2016). However, relatively low calculated penetrance values for SHOX microduplications for ASD (3.6%, 95% CI 2.1%-6.1%) and NDDs (8.7%, 95% CI 5.8%-13.3%) were given in this report. A novel de novo predicted damaging missense variant in SHOX were observed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Reports Added
[New Scoring Scheme]
4/1/2016
icon
3

Increased from to 3

Description

Analysis of aCGH data from a discovery cohort of 90 adult ASD cases and a follow-up cohort of 26,574 patients, including 18,857 cases with NDD (3541 of those with ASD), demonstrated a statistically significant enrichment of SHOX microduplications in NDD cases (P=0.00036; OR=2.21), particularly in those with ASD (P=9.18E-07; OR=3.63), compared with 12,594 controls (Tropeano et al., 2016). However, relatively low calculated penetrance values for SHOX microduplications for ASD (3.6%, 95% CI 2.1%-6.1%) and NDDs (8.7%, 95% CI 5.8%-13.3%) were given in this report. A novel de novo predicted damaging missense variant in SHOX were observed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Krishnan Probability Score

Score 0.58257125267808

Ranking 559/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.73845761042922

Ranking 4275/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.69269553389056

Ranking 1112/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Submit New Gene

Report an Error