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…

Primary Disease Associations & Inheritance

Focal segmental glomerulosclerosis 10MIM #256020

Nail-patella syndromeMIM #161200

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nail-patella syndrome · AD · ClinGen 2021

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.41

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in LMX1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

494 rare PASS variants

Rare truncating (LoF)

1 in 2,200

40 rare PASS variants

Rare synonymous (reference)

1 in 130

254 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LMX1B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 3,100
South Asian	~43k	1 in 200	≈ 1 in 9,600
Remaining (unassigned)	~30k	1 in 220	1 in 1,400
European (Finnish)	~27k	1 in 380	1 in 3,800
Admixed American	~22k	1 in 180	1 in 3,700
African / African American	~21k	1 in 220	≈ 1 in 5,400
East Asian	~20k	1 in 220	1 in 2,900
Ashkenazi Jewish	~13k	1 in 340	none seen
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 8.? see exons ↓