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.

OMIMResearchSummary from UniProt
LOFmechanismLOEUF 0.22
Clinical SummaryLHX2
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 0.988
Z-score 3.39
OE 0.00 (0.000.22)
Highly constrained

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

Missense Constraint
2.27Z-score
OE missense 0.59 (0.510.68)
143 obs / 242.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.22)
00.351.4
Missense OE0.59 (0.510.68)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 0 / 13.4Missense obs/exp: 143 / 242.7Syn Z: -1.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateLHX2-related neurodevelopmental disorder with or without microcephalyLOFAD
DN
0.3892th %ile
GOF
0.3887th %ile
LOF
0.85top 5%

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

LOFprediction above median · LOEUF 0.22

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

LHX2 · 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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