SOX18

Chr 20ARAD

SRY-box transcription factor 18

Also known as: HLTRS, HLTS

SOX18 encodes a transcription factor that activates genes essential for embryonic cardiovascular development, lymphangiogenesis, and hair development by binding to specific promoter sequences. Mutations cause hypotrichosis-lymphedema-telangiectasia syndrome, with or without renal defects, characterized by sparse hair, lymphatic abnormalities, and dilated blood vessels. The condition follows both autosomal recessive and autosomal dominant inheritance patterns.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Hypotrichosis-lymphedema-telangiectasia syndromeMIM #607823
AR
Hypotrichosis-lymphedema-telangiectasia-renal defect syndromeMIM #137940
AD
0
Active trials
26
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.05
LOEUF
DN
Mechanism· predicted
Clinical SummarySOX18
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.05LOEUF
pLI 0.151
Z-score 1.50
OE 0.34 (0.141.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.86Z-score
OE missense 0.79 (0.670.93)
104 obs / 131.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.141.05)
00.351.4
Missense OE0.79 (0.670.93)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 2 / 6.0Missense obs/exp: 104 / 131.8Syn Z: -0.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSOX18-related hypotrichosis-lymphoedema-telangiectasia syndromeOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6065th %ile
GOF
0.5858th %ile
LOF
0.51top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNFunctional analysis confirmed that SOX18wt has potent trans-activation properties, while SOX18DN displays dominant-negative effect.PMID:24460943

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SOX18 · 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

No active trials found for this gene.

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Clinical Literature
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