SOX8

Chr 16

SRY-box transcription factor 8

The SOX8 protein is a transcription factor that binds DNA and regulates embryonic development, particularly in the central nervous system, limbs, and facial structures. Haploinsufficiency causes cognitive disability as part of alpha-thalassemia-related syndrome (ART-16), following an autosomal dominant inheritance pattern. The pathogenic mechanism involves loss of function due to reduced gene dosage affecting normal developmental transcriptional regulation.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
19
Pubs (1 yr)
48
P/LP submissions
0%
P/LP missense
0.51
LOEUF
LOF
Mechanism· predicted
Clinical SummarySOX8
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
47 unique Pathogenic / Likely Pathogenic· 100 VUS of 183 total submissions
📖
GeneReview available — SOX8
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.672
Z-score 2.72
OE 0.16 (0.070.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.89Z-score
OE missense 0.85 (0.760.95)
230 obs / 271.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.070.51)
00.351.4
Missense OE0.85 (0.760.95)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 2 / 12.3Missense obs/exp: 230 / 271.1Syn Z: -1.72
DN
0.5477th %ile
GOF
0.4184th %ile
LOF
0.70top 10%

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

LOFprediction above median

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

ClinVar Variant Classifications

183 submitted variants in ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic1
VUS100
Likely Benign25
Benign9
Conflicting1
46
Pathogenic
1
Likely Pathogenic
100
VUS
25
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
46
0
46
Likely Pathogenic
0
0
1
0
1
VUS
0
83
17
0
100
Likely Benign
0
8
1
16
25
Benign
0
0
3
6
9
Conflicting
1
Total0916822182

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

View in ClinVar →

Protein Context — Lollipop Plot

SOX8 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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