LHX3

Chr 9AR

LIM homeobox 3

Also known as: CPHD3, LIM3, M2-LHX3

NCBI Gene: 8022ENSG00000107187UniProt: Q9UBR4OMIM: 600577

LHX3 encodes a transcription factor that binds to specific DNA sequences to regulate gene expression and is required for pituitary gland development and motor neuron specification. Mutations cause combined pituitary hormone deficiency 3, which involves deficiencies of multiple pituitary hormones and can include motor neuron abnormalities affecting the nervous system. This condition follows autosomal recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.741 OMIM phenotype
Clinical Summary— LHX3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 unique Pathogenic / Likely Pathogenic· 127 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — LHX3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.011
Z-score 2.31
OE 0.38 (0.20–0.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.33Z-score
OE missense 0.94 (0.84–1.05)
218 obs / 232.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.20–0.74)
0≤0.351.4
Missense OE0.94 (0.84–1.05)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 6 / 16.0Missense obs/exp: 218 / 232.3Syn Z: 0.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveLHX3-related pituitary hormone deficiency combinedLOFAR

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

DN
0.74top 25%
GOF
0.6736th %ile
LOF
0.4430th %ile

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.

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

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic17
VUS127
Likely Benign118
Conflicting4
33
Pathogenic
17
Likely Pathogenic
127
VUS
118
Likely Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
26
0
33
Likely Pathogenic
17
0
0
0
17
VUS
0
97
24
6
127
Likely Benign
0
1
38
79
118
Benign
0
0
0
0
0
Conflicting
—4
Total24988885299

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LHX3 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients