SOX5

Chr 12AD

SRY-box transcription factor 5

Also known as: L-SOX5, L-SOX5B, L-SOX5F, LAMSHF

NCBI Gene: 6660ENSG00000134532UniProt: P35711

This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. The encoded protein may play a role in chondrogenesis. A pseudogene of this gene is located on chromosome 8. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Lamb-Shaffer syndromeMIM #616803
AD
1
Active trials
152
Pathogenic / LP
393
ClinVar variants
51
Pubs (1 yr)
3.2
Missense Z· constrained
0.19
LOEUF· LoF intolerant
Clinical Summary— SOX5
🧬
Gene-Disease Validity (ClinGen)
Lamb-Shaffer syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
152 Pathogenic / Likely Pathogenic· 182 VUS of 393 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 5.52
OE 0.07 (0.03–0.19)
Highly constrained

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

Missense Constraint
3.15Z-score
OE missense 0.57 (0.51–0.64)
244 obs / 427.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.03–0.19)
0≤0.351.4
Missense OE0.57 (0.51–0.64)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 3 / 41.2Missense obs/exp: 244 / 427.3Syn Z: -0.21
LOF
DN
0.3296th %ile
GOF
0.3193th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 23% of P/LP variants are LoF · LOEUF 0.19

Literature Evidence

LOFClinical and genetic characterization of a patient with SOX5 haploinsufficiency caused by a de novo balanced reciprocal translocation.PMID:29477873

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

393 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic111
Likely Pathogenic41
VUS182
Likely Benign48
Benign7
Conflicting4
111
Pathogenic
41
Likely Pathogenic
182
VUS
48
Likely Benign
7
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
26
5
80
0
111
Likely Pathogenic
9
18
14
0
41
VUS
4
143
32
3
182
Likely Benign
2
17
9
20
48
Benign
0
0
2
5
7
Conflicting
—4
Total4118313728393

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

SOX5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SOX5-related 12p12.5 intragenic deletions associated with intellectual disability

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
Docherty AR et al.·Am J Psychiatry
2023Meta-analysis
Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency.
Zawerton A et al.·Genet Med
2020
Lamb-Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency.
Tenorio-Castano J et al.·Clin Genet
2023Review
Functional characterization of SOX5 variant causing Lamb-Shaffer syndrome and literature review of variants in the SOX5 gene.
Wang P et al.·Orphanet J Rare Dis
2025Review
Human T-bet governs the generation of a distinct subset of CD11c(high)CD21(low) B cells.
Yang R et al.·Sci Immunol
2022Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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