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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LMBRD1
LMBR1 domain containing 1
Chromosome 6 · 6q13
NCBI Gene: 55788Ensembl: ENSG00000168216.14HGNC: HGNC:23038UniProt: Q9NUN5
29PubMed Papers
21Diseases
0Drugs
57Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
vitamin transmembrane transporter activityprotein localization to lysosomeprotein transporter activitylysosomal membranemethylmalonic aciduria and homocystinuria type cblFMethylmalonic acidemia with homocystinuria type cblFMethylmalonic acidemia with homocystinuriamethylmalonic aciduria and homocystinuria type cblC
✦AI Summary

LMBRD1 encodes a lysosomal membrane protein primarily functioning as a vitamin B₁₂ (cobalamin) exporter 1. The protein contains nine transmembrane domains and shows homology to lipocalin membrane receptors 2. LMBRD1 forms homodimers and interacts with ABCD4 to facilitate vectorial delivery of lysosomal cobalamin to the cytoplasmic protein MMACHC, preventing cofactor dilution and protecting against inactivating reactions 3. Loss-of-function mutations in LMBRD1 cause cblF deficiency, a rare autosomal recessive inborn error of cobalamin metabolism characterized by lysosomal accumulation of free vitamin B₁₂ and impaired synthesis of vitamin B₁₂-dependent enzymes 21. Clinical manifestations include neurological, hematological, developmental, and dermatological defects; patients respond to hydroxocobalamin therapy 4. Heterozygous LMBRD1 knockout in mice causes cardiac hypertrophy, ventricular fibrosis, and impaired cardiac function through altered insulin receptor signaling and increased myocardial glucose uptake, independent of cobalamin transport defects 5. Additionally, LMBRD1 variants associate with methylmalonic aciduria combined with homocystinuria 6 and may contribute to cardiovascular laterality defects 7. LMBRD1 demonstrates prognostic significance in lung adenocarcinoma, where poor expression correlates with worse outcomes 8.

Sources cited
1
LMBRD1 identified as the gene for cblF defect; encodes lysosomal membrane protein; frameshift mutations cause loss of function; wild-type transfection restores cobalamin coenzyme synthesis
PMID: 20446115
2
LMBRD1 encodes LMBD1, a lysosomal membrane protein; mutations identified in cblF individuals; LMBD1 acts as a lysosomal cobalamin exporter
PMID: 19136951
3
LMBD1 and ABCD4 form homodimers and interact with low nanomolar affinity; both interact with cytoplasmic MMACHC; facilitate vectorial delivery of lysosomal vitamin B₁₂
PMID: 25535791
4
LMBRD1 mutations cause cblF deficiency with variable phenotypes including neurological, hematological, developmental, and dermatological defects; novel splice site deletion identified; patients improve with hydroxocobalamin therapy
PMID: 39939801
5
Heterozygous Lmbrd1 knockout causes cardiac hypertrophy, ventricular fibrosis, increased heart rate and contractility, impaired ejection fraction through mechanism independent of cobalamin transport defect
PMID: 28549591
6
LMBRD1 variants cause combined methylmalonic aciduria and homocystinuria
PMID: 40355523
7
Biallelic LMBRD1 variants identified as potential candidate genes in cardiovascular laterality defects
PMID: 35474353
8
LMBRD1 identified as prognostic biomarker in lung adenocarcinoma; poorly expressed in LUAD cell lines and tumor tissues; associated with worse prognosis
PMID: 37577321
Disease Associationsⓘ21
methylmalonic aciduria and homocystinuria type cblFOpen Targets
0.77Strong
Methylmalonic acidemia with homocystinuria type cblFOpen Targets
0.70Strong
Methylmalonic acidemia with homocystinuriaOpen Targets
0.66Moderate
Methylmalonic acidemia with homocystinuria, type cblCOpen Targets
0.50Moderate
methylmalonic aciduria and homocystinuria type cblCOpen Targets
0.50Moderate
genetic disorderOpen Targets
0.41Moderate
homocystinuriaOpen Targets
0.37Weak
methylmalonic aciduria and homocystinuriaOpen Targets
0.37Weak
Vitamin B12-responsive methylmalonic acidemia type cblBOpen Targets
0.37Weak
nephrotic syndromeOpen Targets
0.29Weak
response to antihypertensive drugOpen Targets
0.28Weak
Abnormality of the skeletal systemOpen Targets
0.26Weak
disorders of vitamin D metabolismOpen Targets
0.17Weak
glomerulonephritisOpen Targets
0.17Weak
cutaneous lupus erythematosusOpen Targets
0.16Weak
Donnai-Barrow syndromeOpen Targets
0.12Weak
NephropathyOpen Targets
0.09Suggestive
nephritisOpen Targets
0.08Suggestive
MODYOpen Targets
0.07Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Methylmalonic aciduria and homocystinuria, cblF typeUniProt
Pathogenic Variants57
NM_018368.4(LMBRD1):c.1056del (p.Asn353fs)Pathogenic
Inborn genetic diseases|not provided|Methylmalonic aciduria and homocystinuria type cblF|Disorders of Intracellular Cobalamin Metabolism|Cobalamin C disease|LMBRD1-related disorder
★★☆☆2026→ Residue 353
NM_018368.4(LMBRD1):c.399del (p.Lys133fs)Pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★★☆☆2025→ Residue 133
NM_018368.4(LMBRD1):c.562+1G>ALikely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★★☆☆2024
NM_018368.4(LMBRD1):c.515_516del (p.Thr172fs)Pathogenic
Methylmalonic aciduria and homocystinuria type cblF|not provided|Cobalamin C disease
★★☆☆2024→ Residue 172
NM_018368.4(LMBRD1):c.967_970del (p.Leu323fs)Pathogenic
Methylmalonic aciduria and homocystinuria type cblF|Cobalamin C disease
★★☆☆2024→ Residue 323
NM_018368.4(LMBRD1):c.763-2A>GLikely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★★☆☆2024
NM_018368.4(LMBRD1):c.1187_1188+2delLikely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★★☆☆2024
NM_018368.4(LMBRD1):c.762+1G>ALikely pathogenic
LMBRD1-related disorder|Methylmalonic aciduria and homocystinuria type cblF
★★☆☆2023
NM_018368.4(LMBRD1):c.1339-1G>TPathogenic
Methylmalonic aciduria and homocystinuria type cblF
★★☆☆2023
NM_018368.4(LMBRD1):c.1338+1G>CLikely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2026
NM_018368.4(LMBRD1):c.1067del (p.Leu356fs)Pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2025→ Residue 356
NM_018368.4(LMBRD1):c.63dup (p.Leu22fs)Pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024→ Residue 22
NC_000006.12:g.69697707_69697708insTATCAGATTATCAGAAGTTATATTAGTCTGAAAGATAAAAATACAGTTAAAATATAAAAACCGCATTAATAAATACATTTGGATTTAAAAAGTPathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024
NM_018368.4(LMBRD1):c.562+1delLikely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024
NM_018368.4(LMBRD1):c.1187_1188+3delLikely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024
NM_018368.4(LMBRD1):c.632dup (p.Tyr211Ter)Likely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024→ Residue 211
NM_018368.4(LMBRD1):c.760A>T (p.Lys254Ter)Likely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024→ Residue 254
NM_018368.4(LMBRD1):c.44G>A (p.Trp15Ter)Likely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024→ Residue 15
NM_018368.4(LMBRD1):c.553G>T (p.Gly185Ter)Likely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024→ Residue 185
NM_018368.4(LMBRD1):c.562+1G>TLikely pathogenic
Methylmalonic aciduria and homocystinuria type cblF
★☆☆☆2024
View on ClinVar ↗
Related Genes
MMAAProtein interaction100%MMABProtein interaction97%MMACHCProtein interaction93%MTRProtein interaction83%MTRRProtein interaction83%MMUTProtein interaction83%
Tissue Expression6 tissues
Brain
100%
Heart
61%
Liver
57%
Ovary
44%
Lung
39%
Bone Marrow
34%
Gene Interaction Network
Click a node to explore
LMBRD1MMAAMMABMMACHCMTRMTRRMMUT
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9NUN5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.18LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.89 [0.67–1.18]
RankingsWhere LMBRD1 stands among ~20K protein-coding genes
  • #12,177of 20,598
    Most Researched29
  • #1,221of 5,498
    Most Pathogenic Variants57 · top quartile
  • #12,428of 17,882
    Most Constrained (LOEUF)1.18
Genes detectedLMBRD1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
LMBRD1: the gene for the cblF defect of vitamin B₁₂ metabolism.
PMID: 20446115
J Inherit Metab Dis · 2011
1.00
2
PMID: 20301503
0.90
3
Identification of lysosomal genes associated with prognosis in lung adenocarcinoma.
PMID: 37577321
Transl Lung Cancer Res · 2023
0.80
4
Phenotype puzzle: the role of novel LMBRD1 gene variant in Cbl deficiency causing Dyskeratosis Congenita-like clinical manifestations.
PMID: 39939801
J Hum Genet · 2025
0.70
5
Spectrum of genetic mutations in methylmalonic aciduria among Iranian patients.
PMID: 40355523
Sci Rep · 2025
0.60