LHX8
Chr 1LIM homeobox 8
Also known as: LHX7
LHX8 encodes a LIM homeobox transcription factor that regulates neuronal differentiation and tooth morphogenesis. Mutations cause autosomal recessive hypogonadotropic hypogonadism with absent or delayed puberty, and may be associated with dental abnormalities including cleft palate and odontoma formation. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.47), suggesting intolerance to complete protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
78 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 18 | 0 | 18 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 44 | 4 | 0 | 48 |
Likely Benign | 0 | 1 | 2 | 3 | 6 |
Benign | 0 | 1 | 0 | 2 | 3 |
| Total | 0 | 46 | 26 | 5 | 77 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LHX8 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools