LMX1A

Chr 1AD

LIM homeobox transcription factor 1 alpha

Also known as: DFNA7, LMX1, LMX1.1

LMX1A encodes a transcription factor that activates insulin gene transcription and is required for roof plate development in the central nervous system and specification of dorsal cell fates during embryogenesis. Mutations cause autosomal dominant nail-patella syndrome, characterized by nail dysplasia, absent or hypoplastic patellae, elbow abnormalities, and nephropathy. The gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 0.271 OMIM phenotype
Clinical SummaryLMX1A
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Gene-Disease Validity (ClinGen)
autosomal dominant nonsyndromic hearing loss · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.991
Z-score 4.06
OE 0.09 (0.040.27)
Highly constrained

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

Missense Constraint
1.00Z-score
OE missense 0.81 (0.710.92)
175 obs / 216.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.040.27)
00.351.4
Missense OE0.81 (0.710.92)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 2 / 23.0Missense obs/exp: 175 / 216.5Syn Z: 0.56
DN
0.4686th %ile
GOF
0.3887th %ile
LOF
0.76top 10%

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

LOFprediction above median · 1 literature citation · LOEUF 0.27

Literature Evidence

LOFFurther, our dominant LMX1A variant exerted pathogenic effects via haploinsufficiency rather than dominant-negative effect.PMID:32840933

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

LMX1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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