LHX6

Chr 9

LIM homeobox 6

Also known as: LHX6.1, hLHX6

This gene encodes a transcription factor that regulates GABAergic interneuron development and migration from the subpallium to the cerebral cortex. Mutations cause autosomal dominant intellectual disability with corpus callosum abnormalities, epilepsy, and developmental delays. The gene is highly constrained against loss-of-function variants (pLI 0.97), indicating that such mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.33
Clinical SummaryLHX6
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.966
Z-score 3.65
OE 0.10 (0.040.33)
Highly constrained

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

Missense Constraint
2.93Z-score
OE missense 0.46 (0.390.54)
104 obs / 228.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.040.33)
00.351.4
Missense OE0.46 (0.390.54)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 2 / 19.3Missense obs/exp: 104 / 228.4Syn Z: 1.01
DN
0.3892th %ile
GOF
0.3986th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.33

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LHX6 · 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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