LMBRD1 (LMBR1 domain containing 1)

Gene

• Entrez ID: 55788
• Gene name: LMBR1 domain containing 1
• Gene symbol: LMBRD1
• Synonyms (NCBI Gene): C6orf209, LMBD1, MAHCF, NESI
• Chromosome: 6
• Chromosome location: 6q13
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200639044	C>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs749272546	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs779151199	GT>-	Pathogenic	Frameshift variant, coding sequence variant
rs1562112641	G>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019020	hsa-miR-335-5p	Microarray	18185580
MIRT1111476	hsa-miR-1305	CLIP-seq
MIRT1111477	hsa-miR-3609	CLIP-seq
MIRT1111478	hsa-miR-3613-3p	CLIP-seq
MIRT1111479	hsa-miR-4307	CLIP-seq
MIRT1111480	hsa-miR-4504	CLIP-seq
MIRT1111481	hsa-miR-4795-3p	CLIP-seq
MIRT1111482	hsa-miR-548ah	CLIP-seq
MIRT1111483	hsa-miR-548t	CLIP-seq
MIRT1111484	hsa-miR-607	CLIP-seq
MIRT2031128	hsa-miR-376c	CLIP-seq
MIRT2031129	hsa-miR-584	CLIP-seq
MIRT2561781	hsa-miR-200b	CLIP-seq
MIRT2561782	hsa-miR-200c	CLIP-seq
MIRT2561783	hsa-miR-3163	CLIP-seq
MIRT2561784	hsa-miR-3651	CLIP-seq
MIRT2561785	hsa-miR-3682-5p	CLIP-seq
MIRT2561786	hsa-miR-369-3p	CLIP-seq
MIRT2561787	hsa-miR-374a	CLIP-seq
MIRT2561788	hsa-miR-374b	CLIP-seq
MIRT2561789	hsa-miR-374c	CLIP-seq
MIRT2561790	hsa-miR-409-3p	CLIP-seq
MIRT2561791	hsa-miR-429	CLIP-seq
MIRT2561792	hsa-miR-4666-3p	CLIP-seq
MIRT2561793	hsa-miR-4766-3p	CLIP-seq
MIRT2561794	hsa-miR-511	CLIP-seq
MIRT2561795	hsa-miR-548c-3p	CLIP-seq
MIRT2561796	hsa-miR-548p	CLIP-seq
MIRT2561797	hsa-miR-570	CLIP-seq
MIRT2561798	hsa-miR-655	CLIP-seq
MIRT2561781	hsa-miR-200b	CLIP-seq
MIRT2561782	hsa-miR-200c	CLIP-seq
MIRT2561783	hsa-miR-3163	CLIP-seq
MIRT2561784	hsa-miR-3651	CLIP-seq
MIRT2561785	hsa-miR-3682-5p	CLIP-seq
MIRT2561786	hsa-miR-369-3p	CLIP-seq
MIRT2561787	hsa-miR-374a	CLIP-seq
MIRT2561788	hsa-miR-374b	CLIP-seq
MIRT2561789	hsa-miR-374c	CLIP-seq
MIRT2561790	hsa-miR-409-3p	CLIP-seq
MIRT2561791	hsa-miR-429	CLIP-seq
MIRT2561792	hsa-miR-4666-3p	CLIP-seq
MIRT2561793	hsa-miR-4766-3p	CLIP-seq
MIRT2561794	hsa-miR-511	CLIP-seq
MIRT2561796	hsa-miR-548p	CLIP-seq
MIRT2561797	hsa-miR-570	CLIP-seq
MIRT2561798	hsa-miR-655	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005158	Function	Insulin receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	25535791, 27456980, 28572511, 32296183, 33845046
GO:0005764	Component	Lysosome	IEA
GO:0005765	Component	Lysosomal membrane	IBA
GO:0005765	Component	Lysosomal membrane	IDA	27456980
GO:0005765	Component	Lysosomal membrane	IEA
GO:0005765	Component	Lysosomal membrane	TAS
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	27456980
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	ISS
GO:0006897	Process	Endocytosis	IEA
GO:0007369	Process	Gastrulation	IEA
GO:0007369	Process	Gastrulation	ISS
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IEA
GO:0030136	Component	Clathrin-coated vesicle	IEA
GO:0030136	Component	Clathrin-coated vesicle	ISS
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0031419	Function	Cobalamin binding	IEA
GO:0032050	Function	Clathrin heavy chain binding	IEA
GO:0032050	Function	Clathrin heavy chain binding	ISS
GO:0035612	Function	AP-2 adaptor complex binding	IEA
GO:0035612	Function	AP-2 adaptor complex binding	ISS
GO:0038016	Process	Insulin receptor internalization	IEA
GO:0038016	Process	Insulin receptor internalization	ISS
GO:0045334	Component	Clathrin-coated endocytic vesicle	IEA
GO:0045334	Component	Clathrin-coated endocytic vesicle	ISS
GO:0061462	Process	Protein localization to lysosome	IBA
GO:0061462	Process	Protein localization to lysosome	IDA	27456980
GO:0072583	Process	Clathrin-dependent endocytosis	IEA
GO:0072583	Process	Clathrin-dependent endocytosis	ISS
GO:0140318	Function	Protein transporter activity	IDA	27456980, 33845046

Other IDs

• MIM: 612625
• HGNC: 23038
• e!Ensembl: ENSG00000168216

Protein

• UniProt ID: Q9NUN5
• Protein name: Lysosomal cobalamin transport escort protein LMBD1 (LMBD1) (HDAg-L-interacting protein NESI) (LMBR1 domain-containing protein 1) (Nuclear export signal-interacting protein)
• Protein function: Lysosomal membrane chaperone required to export cobalamin (vitamin B12) from the lysosome to the cytosol, allowing its conversion to cofactors (PubMed:19136951). Targets ABCD4 transporter from the endoplasmic reticulum to the lysosome (PubMed:27
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04791	LMBR1	14 → 428	LMBR1-like membrane protein	Family

• Tissue specificity: TISSUE SPECIFICITY: Isoform 3 is expressed in liver. {ECO:0000269|PubMed:15956556}.
• Sequence:

  MATSGAASAELVIGWCIFGLLLLAILAFCWIYVRKYQSRRESEVVSTITAIFSLAIALIT
  SALLPVDIFLVSYMKNQNGTFKDWANANVSRQIEDTVLYGYYTLYSVILFCVFFWIPFVY
  FYYEEKDDDDTSKCTQIKTALKYTLGFVVICALLLLVGAFVPLNVPNNKNSTEWEKVKSL
  FEELGSSHGLAALSFSISSLTLIGMLAAITYTAYGMSALPLNLIKGTRSAAYERLENTED
  IEEVEQHIQTIKSKSKDGRPLPARDKRALKQFEERLRTLKKRERHLEFIENSWWTKFCGA
  LRPLKIVWGIFFILVALLFVISLFLSNLDKALHSAGIDSGFIIFGANLSNPLNMLLPLLQ
  TVFPLDYILITIIIMYFIFTSMAGIRNIGIWFFWIRLYKIRRGRTRPQALLFLCMILLLI
  VLHTSYMIYSLAPQYVMYGSQNYLIETNITSDNHKGNSTLSVPKRCDADAPEDQCTVTRT
  YLFLHKFWFFSAAYYFGNWAFLGVFLIGLIVSCCKGKKSVIEGVDEDSDISDDEPSVYSA
  

• Sequence length: 540

Pathways

KEGG:

Vitamin digestion and absorption
Cobalamin transport and metabolism

Reactome:

Cobalamin (Cbl, vitamin B12) transport and metabolism
Defective LMBRD1 causes methylmalonic aciduria and homocystinuria type cblF

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Cobalamin C disease	Likely pathogenic; Pathogenic	rs771477094, rs779151199, rs764930914, rs749272546, rs2482221339	RCV004770134 RCV004782001 RCV002238651 RCV002509305 RCV003155826	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Disorders of Intracellular Cobalamin Metabolism	Pathogenic	rs749272546	RCV002517437	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
LMBRD1-related disorder	Pathogenic; Likely pathogenic	rs749272546, rs374040562	RCV004752799 RCV003402078	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Methylmalonic aciduria and homocystinuria type cblF	Likely pathogenic; Pathogenic	rs771477094, rs768709895, rs1562112648, rs2149843526, rs372279393, rs779151199, rs1562112641, rs2149844541, rs2481466497, rs749272546, rs1767108423, rs374040562, rs2481328329, rs768207964, rs1766552940, rs2481499681, rs1170149970, rs2481410901, rs2481466290, rs2481327951, rs2482221144, rs2481485775, rs2481385860, rs2482221622, rs2481328299, rs2481377410, rs773154173, rs758107642, rs2481411386, rs2482216432, rs1767111402, rs35350789, rs561314652, rs1026913794, rs141038315, rs1765174711, rs779142724, rs2481411360, rs867010959, rs1380343985	RCV001382038 RCV001783602 RCV001864637 RCV002050023 RCV001975694 RCV000000546 RCV000000547 RCV002251001 RCV002715954 RCV000778799 RCV003313906 RCV003778214 RCV003496219 RCV003496440 RCV003496266 RCV003496306 RCV003497100 RCV003494785 RCV003494768 RCV003494660 RCV003495032 RCV003496012 RCV003495611 RCV003495922 RCV003496693 RCV003598235 RCV003598859 RCV003598383 RCV003598906 RCV003599157 RCV003599474 RCV003599506 RCV003597821 RCV003598496 RCV003598747 RCV003838357 RCV003835397 RCV003846272 RCV003865519 RCV003868050 RCV003876391 RCV003867611 RCV001050843	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Donnai-Barrow syndrome	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glioma susceptibility 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METHYLMALONIC ACIDEMIA WITH HOMOCYSTINURIA TYPE CBLF	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, CBLF TYPE	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-ALCOHOLIC FATTY LIVER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia, Megaloblastic	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital small ears	Microtia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cystathioninemia	Cystathioninemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gamma-cystathionase deficiency	Gamma-Cystathionase Deficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glossitis	Glossitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Homocystinuria	Homocystinuria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia	Methylmalonic acidemia	Pubtator	35361390	Associate	★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia with homocystinuria	Methylmalonic acidemia	Pubtator	34655177	Associate	★☆☆☆☆ Found in Text Mining only
Methylmalonic acidemia with homocystinuria type cblF	Methylmalonic Acidemia With Homocystinuria	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Methylmalonic Aciduria and Homocystinuria CblF Type	Methylmalonic acidemia	Pubtator	22922874	Associate	★☆☆☆☆ Found in Text Mining only
METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblF TYPE (disorder)	Methylmalonic acidemia with homocystinuria	GENOMICS_ENGLAND_DG	19136951, 27604308		★☆☆☆☆ Found in Text Mining only
METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblF TYPE (disorder)	Methylmalonic acidemia with homocystinuria	CLINVAR_DG	19136951, 21303734, 24664876, 26997947		★☆☆☆☆ Found in Text Mining only
METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblF TYPE (disorder)	Methylmalonic acidemia with homocystinuria	BEFREE	20446115, 21910240, 23776111		★☆☆☆☆ Found in Text Mining only
METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblF TYPE (disorder)	Methylmalonic acidemia with homocystinuria	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Neutropenia	Neutropenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancytopenia	Pancytopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomatitis	Stomatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only