LMX1B

Chr 9AD

LIM homeobox transcription factor 1 beta

Also known as: FSGS10, LMX1.2, NPS1

NCBI Gene: 4010 ENSG00000136944 UniProt: O60663 OMIM: 602575

This transcription factor is essential for normal development of dorsal limb structures, the glomerular basement membrane, the anterior eye segment, and dopaminergic and serotonergic neurons. Mutations cause nail-patella syndrome, an autosomal dominant disorder characterized by nail dysplasia, absent or hypoplastic patellae, elbow abnormalities, and nephropathy that can progress to chronic kidney disease. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.415), consistent with its role in multiple developmental processes.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of LIM-homeodomain family of proteins containing two N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. It functions as a transcription factor, and is essential for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Mutations in this gene are associated with nail-patella syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.412 OMIM phenotypes

Clinical Summary— LMX1B

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Gene-Disease Validity (ClinGen)

nail-patella syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.

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ClinVar Variants

158 unique Pathogenic / Likely Pathogenic· 270 VUS of 708 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — LMX1B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.18 (0.09–0.41)

0≤0.351.4

Missense OE?0.65 (0.57–0.74)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 4 / 22.1Missense obs/exp: 169 / 260.8Syn Z: -0.81

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveLMX1B-related nail-patella syndromeLOFAD

This gene — mechanism propensity

0.5379th %ile

GOF

0.4480th %ile

LOF

0.68top 10%

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

LOFprediction above median · 1 literature citation · 63% of P/LP variants are LoF · LOEUF 0.41 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFLoss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 9618165 ↗

ClinVar Variant Classifications

708 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic117

Likely Pathogenic41

VUS270

Likely Benign167

Benign84

Conflicting25

117

Pathogenic

Likely Pathogenic

270

VUS

167

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	83	24	10	0	117
Likely Pathogenic	16	22	3	0	41
VUS	2	163	101	4	270
Likely Benign	2	7	67	91	167
Benign	0	0	79	5	84
Conflicting	—				25
Total	103	216	260	100	704

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap LMX1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →