SOX15

Chr 17

SRY-box transcription factor 15

Also known as: SOX20, SOX26, SOX27

NCBI Gene: 6665 ENSG00000129194 UniProt: O60248 OMIM: 601297

SOX15 encodes a transcription factor that regulates muscle development and regeneration by binding to specific DNA sequences and controlling expression of muscle-specific genes including MYOD and MYOG. Currently, no definitive human diseases have been established from SOX15 mutations in the medical literature. The gene shows relatively low constraint against loss-of-function variants, suggesting that complete loss may be tolerated in humans.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.90

Clinical Summary— SOX15

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

34 VUS of 37 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.215

Z-score 1.76

OE 0.28 (0.12–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.62Z-score

OE missense 0.85 (0.72–0.99)

109 obs / 128.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.12–0.90)

0≤0.351.4

Missense OE?0.85 (0.72–0.99)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 2 / 7.0Missense obs/exp: 109 / 128.9Syn Z: 0.56

This gene — mechanism propensity

0.6647th %ile

GOF

0.5170th %ile

LOF

0.48top 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.

ClinVar Variant Classifications

37 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	33	1	34
Likely Benign	3	0	3
Benign	0	0	0
Total	36	1	37

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap SOX15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →