LMBR1

Chr 7ARAD

limb development membrane protein 1

Also known as: ACHP, C7orf2, DIF14, LSS, PPD2, THYP, TPT, TPTPS

NCBI Gene: 64327ENSG00000105983UniProt: Q8WVP7

This gene encodes a member of the LMBR1-like membrane protein family. Another member of this protein family has been shown to be a lipocalin transmembrane receptor. A highly conserved, cis-acting regulatory module for the sonic hedgehog gene is located within an intron of this gene. Consequently, disruption of this genic region can alter sonic hedgehog expression and affect limb patterning, but it is not known if this gene functions directly in limb development. Mutations and chromosomal deletions and rearrangements in this genic region are associated with acheiropody and preaxial polydactyly, which likely result from altered sonic hedgehog expression. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

AcheiropodyMIM #200500
AR
Laurin-Sandrow syndromeMIM #135750
AD
Syndactyly, type IVMIM #186200
AD
Triphalangeal thumb-polysyndactyly syndromeMIM #190605
AD
UniProtPreaxial polydactyly 2
UniProtSyndactyly 4
UniProtHypoplasia or aplasia of tibia with polydactyly
542
ClinVar variants
95
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LMBR1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
95 Pathogenic / Likely Pathogenic· 256 VUS of 542 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.83LOEUF
pLI 0.000
Z-score 2.33
OE 0.56 (0.38–0.83)
Tolerant

Typical tolerance to LoF variation

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.
0.85Z-score
OE missense 0.85 (0.76–0.95)
206 obs / 243.3 exp
Tolerant

Mild missense constraint

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.0.56 (0.38–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.76–0.95)
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.0.97
0≤1.21.6
LoF obs/exp: 18 / 32.3Missense obs/exp: 206 / 243.3Syn Z: 0.20

ClinVar Variant Classifications

542 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic11
VUS256
Likely Benign98
Benign91
Conflicting2
84
Pathogenic
11
Likely Pathogenic
256
VUS
98
Likely Benign
91
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
84
0
84
Likely Pathogenic
0
0
11
0
11
VUS
4
88
162
2
256
Likely Benign
0
3
82
13
98
Benign
0
1
89
1
91
Conflicting
—2
Total49242816542

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

View in ClinVar →

Protein Context — Lollipop Plot

LMBR1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Acheiropody

MIM #200500

Molecular basis of disorder known

Autosomal recessive

Laurin-Sandrow syndrome

MIM #135750

Molecular basis of disorder known

Autosomal dominant

Syndactyly, type IV

MIM #186200

Molecular basis of disorder known

Autosomal dominant

Triphalangeal thumb-polysyndactyly syndrome

MIM #190605

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — LMBR1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of an alternative splicing isoform of chicken Lmbr1.
Huang Y et al.·Mol Biol Rep
2011
Reciprocal mouse and human limb phenotypes caused by gain- and loss-of-function mutations affecting Lmbr1.
Clark RM et al.·Genetics
2001Functional
Isolation of the chicken Lmbr1 coding sequence and characterization of its role during chick limb development.
Maas SA et al.·Dev Dyn
2004
Large duplication in LMBR1 gene in a large Chinese pedigree with triphalangeal thumb polysyndactyly syndrome.
Xu J et al.·Am J Med Genet A
2020
[Analysis of gene variant in a Chinese pedigree with preaxial polydactyly].
Li Z et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2021
A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies.
Álvarez LFG et al.·Am J Med Genet A
2023
A novel candidate gene for mouse and human preaxial polydactyly with altered expression in limbs of Hemimelic extra-toes mutant mice.
Clark RM et al.·Genomics
2000Functional
Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene.
Ianakiev P et al.·Am J Hum Genet
2001
Mutation analysis of a large Chinese pedigree with congenital preaxial polydactyly.
Li H et al.·Eur J Hum Genet
2009
[Progress on polydactyly character of vertebrate].
Huang YQ et al.·Yi Chuan
2004Review
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