SOX4

Chr 6AD

SRY-box transcription factor 4

Also known as: CSS10, EVI16, IDDSDF

NCBI Gene: 6659ENSG00000124766UniProt: Q06945OMIM: 184430

The SOX4 protein is a transcription factor that regulates embryonic development, cell fate determination, and skeletal muscle differentiation by binding to specific DNA sequences and activating gene expression. Mutations cause autosomal dominant intellectual developmental disorder with speech delay and dysmorphic facies. This gene is highly constrained against loss-of-function variants (pLI 0.93, LOEUF 0.36), indicating that mutations are likely to have significant clinical consequences.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.361 OMIM phenotype
Clinical Summary— SOX4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 129 VUS of 186 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — SOX4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.36LOEUF
pLI 0.927
Z-score 2.68
OE 0.00 (0.00–0.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.17Z-score
OE missense 0.77 (0.67–0.88)
150 obs / 196.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.36)
0≤0.351.4
Missense OE0.77 (0.67–0.88)
0≤0.61.4
Synonymous OE1.67
0≤1.21.6
LoF obs/exp: 0 / 8.3Missense obs/exp: 150 / 196.0Syn Z: -5.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSOX4-related neurodevelopmental disease associated with mild dysmorphismOTHERAD
DN
0.2698th %ile
GOF
0.2895th %ile
LOF
0.89top 5%

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

LOFprediction above median · 18% of P/LP variants are LoF · LOEUF 0.36

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

186 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic11
VUS129
Likely Benign17
Benign6
Conflicting6
17
Pathogenic
11
Likely Pathogenic
129
VUS
17
Likely Benign
6
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
13
0
17
Likely Pathogenic
2
9
0
0
11
VUS
12
113
3
1
129
Likely Benign
0
3
1
13
17
Benign
0
2
2
2
6
Conflicting
—6
Total171281916186

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

View in ClinVar →

Protein Context — Lollipop Plot

SOX4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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
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