LHX2
Chr 9LIM homeobox 2
Also known as: LH2, hLhx2
LHX2 encodes a transcription factor that regulates cell differentiation in developing lymphoid and neural tissues and acts as a transcriptional activator. Mutations cause autosomal dominant developmental abnormalities affecting the nervous system and other organ systems. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.22), indicating that even single functional copies are critical for normal development.
Strong evidence — appropriate for clinical testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
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
101 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 | 4 | 2 | 27 | 0 | 33 |
Likely Pathogenic | 1 | 0 | 1 | 0 | 2 |
VUS | 5 | 50 | 2 | 1 | 58 |
Likely Benign | 0 | 2 | 0 | 3 | 5 |
Benign | 0 | 1 | 0 | 1 | 2 |
| Total | 10 | 55 | 30 | 5 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LHX2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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