LMX1B

Chr 9AD

LIM homeobox transcription factor 1 beta

NCBI Gene: 4010ENSG00000136944UniProt: O60663

Transcription factor involved in the regulation of podocyte-expressed genes (PubMed:24042019, PubMed:28059119). Essential for the specification of dorsal limb fate at both the zeugopodal and autopodal levels

Primary Disease Associations & Inheritance

Focal segmental glomerulosclerosis 10MIM #256020
AD
Nail-patella syndromeMIM #161200
AD
752
ClinVar variants
126
Pathogenic / LP
0.75
pLI score
0
Active trials
Clinical Summary— LMX1B
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
126 Pathogenic / Likely Pathogenic· 205 VUS of 752 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.41LOEUF
pLI 0.746
Z-score 3.56
OE 0.18 (0.09–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.02Z-score
OE missense 0.65 (0.57–0.74)
169 obs / 260.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.09–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.57–0.74)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 4 / 22.1Missense obs/exp: 169 / 260.8Syn Z: -0.81

ClinVar Variant Classifications

752 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic94
Likely Pathogenic32
VUS205
Likely Benign121
Benign26
Conflicting18
94
Pathogenic
32
Likely Pathogenic
205
VUS
121
Likely Benign
26
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
34
16
44
0
94
Likely Pathogenic
11
16
5
0
32
VUS
2
132
69
2
205
Likely Benign
0
5
46
70
121
Benign
0
0
25
1
26
Conflicting
—18
Total4716918973496

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

View in ClinVar →

Protein Context — Lollipop Plot

LMX1B · protein map & ClinVar variants

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

Gene2Phenotype Curations

LMX1B-related nail-patella syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkinSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Focal segmental glomerulosclerosis 10

MIM #256020

Molecular basis of disorder known

Autosomal dominant

Nail-patella syndrome

MIM #161200

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Collagenofibrotic Glomerulopathy.
Miyake M et al.·Intern Med
2021Case report
Collagen Type III Glomerulopathies.
Cohen AH·Adv Chronic Kidney Dis
2012Review
Sequential prenatal diagnosis of fetal skeletal dysplasia: A cohort study.
Jiang M et al.·Acta Obstet Gynecol Scand
2025Cohort
Exome sequencing of 1190 non-syndromic clubfoot cases reveals HOXD12 as a novel disease gene.
Charng WL et al.·J Med Genet
2024Cohort
LMX1B-associated gankyrin expression predicts poor prognosis in glioma patients.
Guo X et al.·J Int Med Res
2020Cohort
Renal phenotype in heterozygous Lmx1b knockout mice (Lmx1b+/-) after unilateral nephrectomy.
Endele S et al.·Transgenic Res
2007
Potential Involvements of Anterior Segment Dysgenesis-Associated Genes in Primary Congenital Glaucoma.
Pyatla G et al.·Semin Ophthalmol
2025Review
Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome.
Akçimen F et al.·Ann Neurol
2024Meta-analysis
Nail-patella syndrome. Overview on clinical and molecular findings.
Bongers EM et al.·Pediatr Nephrol
2002Review
The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.
Dunston JA et al.·Genomics
2004
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools