LMBRD1

Chr 6AR

LMBR1 domain containing 1

Also known as: C6orf209, LMBD1, MAHCF, NESI

NCBI Gene: 55788ENSG00000168216UniProt: Q9NUN5

This gene encodes a lysosomal membrane protein that may be involved in the transport and metabolism of cobalamin. This protein also interacts with the large form of the hepatitis delta antigen and may be required for the nucleocytoplasmic shuttling of the hepatitis delta virus. Mutations in this gene are associated with the vitamin B12 metabolism disorder termed, homocystinuria-megaloblastic anemia complementation type F.[provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Methylmalonic aciduria and homocystinuria, cblF typeMIM #277380
AR
Methylmalonic aciduria and homocystinuria, cblJ typeMIM #614857
AR
Methylmalonic aciduria and homocystinuria, cblF typeMIM #277380
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LMBRD1
🧬
Gene-Disease Validity (ClinGen)
methylmalonic aciduria and homocystinuria type cblF · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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.
0.93LOEUF
pLI 0.000
Z-score 1.88
OE 0.64 (0.46–0.93)
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.
0.26Z-score
OE missense 0.96 (0.87–1.06)
272 obs / 284.2 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.0.64 (0.46–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.87–1.06)
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.0.93
0≤1.21.6
LoF obs/exp: 21 / 32.6Missense obs/exp: 272 / 284.2Syn Z: 0.56

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

LMBRD1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

LMBRD1-related methylmalonic aciduria and homocystinuria

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

3 OMIM entries

OMIM

Methylmalonic aciduria and homocystinuria, cblF type

MIM #277380

Molecular basis of disorder known

Autosomal recessive

Methylmalonic aciduria and homocystinuria, cblJ type

MIM #614857

Molecular basis of disorder known

Autosomal recessive

Methylmalonic aciduria and homocystinuria, cblF type

MIM #277380

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — LMBRD1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Phenotype puzzle: the role of novel LMBRD1 gene variant in Cbl deficiency causing Dyskeratosis Congenita-like clinical manifestations.
Shah A et al.·J Hum Genet
2025Case report
Exome sequencing in individuals with cardiovascular laterality defects identifies potential candidate genes.
Breuer K et al.·Eur J Hum Genet
2022
Cobalamin F deficiency in a girl with severe skin hyperpigmentation and a homozygous LMBRD1 variant.
Braz SV et al.·Clin Exp Dermatol
2022Case report
A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient.
Gailus S et al.·J Inherit Metab Dis
2010
Clinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B(12)-trafficking proteins ABCD4 and LMBD1.
Fettelschoss V et al.·J Biol Chem
2017
[Differential diagnosis of a Chinese pedigree with methylmalonic acidemia by next-generation sequencing].
Zhao G et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2022
The lysosomal protein ABCD4 can transport vitamin B(12) across liposomal membranes in vitro.
Kitai K et al.·J Biol Chem
2021
Dissecting the role of vitamin B(12) metabolism in craniofacial development through analysis of clinical phenotypes and model organism discoveries.
Pinales BE et al.·Differentiation
2025Review
The genotype analysis and prenatal genetic diagnosis among 244 pedigrees with methylmalonic aciduria in China.
Hu S et al.·Taiwan J Obstet Gynecol
2022
Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis.
Hwang N et al.·Mol Genet Genomic Med
2021Case report
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