LMBRD1

LMBR1 domain containing 1

Basic information

Region (hg38): 6:69672756-69867236

Previous symbols: [ "C6orf209" ]

Links

ENSG00000168216 ∙ NCBI:55788 ∙ OMIM:612625 ∙ HGNC:23038 ∙ Uniprot:Q9NUN5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• methylmalonic aciduria and homocystinuria type cblF (Definitive), mode of inheritance: AR
• methylmalonic aciduria and homocystinuria type cblF (Strong), mode of inheritance: AR
• methylmalonic aciduria and homocystinuria type cblF (Strong), mode of inheritance: AR
• methylmalonic aciduria and homocystinuria type cblF (Supportive), mode of inheritance: AR
• methylmalonic aciduria and homocystinuria type cblF (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Methylmalonic aciduria and homocystinuria, cblF type	AR	Biochemical	While no treatment is completely effective, specific dietary (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation) and other medical measures (eg, cofactor therapy with hydroxycobalamin) may be beneficial to treat and prevent sequelae in the acute and chronic states	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Dermatologic; Hematologic; Neurologic	4001945; 3725502; 20301503; 19136951; 20127417; 21910240; 21303734; 22065268; 20446115

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMBRD1 gene.

• Methylmalonic aciduria and homocystinuria type cblF (251 variants)
• not provided (60 variants)
• Inborn genetic diseases (28 variants)
• not specified (20 variants)
• Disorders of Intracellular Cobalamin Metabolism (8 variants)
• Cobalamin C disease (3 variants)
• LMBRD1-related condition (1 variants)
• Donnai-Barrow syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMBRD1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	41	2	47
missense			96	1	1	98
nonsense	4	1				5
start loss						0
frameshift	7	4				11
inframe indel						0
splice donor/acceptor (+/-2bp)		10				10
splice region	1		1	20	1	23
non coding			16	66	34	116
Total	11	15	116	108	37

Highest pathogenic variant AF is 0.000586

Variants in LMBRD1

This is a list of pathogenic ClinVar variants found in the LMBRD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-69675763-A-G		Methylmalonic aciduria and homocystinuria type cblF	Benign (Jan 13, 2018)
6-69675774-T-G		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (Feb 02, 2018)
6-69675817-G-A		Methylmalonic aciduria and homocystinuria type cblF	Benign (Jan 12, 2018)
6-69675938-C-A		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (Jan 13, 2018)
6-69675992-T-C		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (Apr 27, 2017)
6-69676033-T-C		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (Jan 13, 2018)
6-69676081-C-A		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (Jan 12, 2018)
6-69676132-T-C		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (Jan 13, 2018)
6-69676167-A-G		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Apr 15, 2023)
6-69676168-T-C		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (Aug 10, 2022)
6-69676170-G-C		Methylmalonic aciduria and homocystinuria type cblF	Conflicting classifications of pathogenicity (Jul 28, 2023)
6-69676176-G-C		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Apr 10, 2023)
6-69676182-A-G		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Nov 09, 2023)
6-69676204-T-C		Methylmalonic aciduria and homocystinuria type cblF • Inborn genetic diseases	Uncertain significance (Jun 27, 2023)
6-69676209-T-C		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Oct 20, 2023)
6-69676224-C-A		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Oct 16, 2023)
6-69676224-C-T		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Dec 20, 2023)
6-69676225-G-A		Methylmalonic aciduria and homocystinuria type cblF • Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
6-69676243-C-T		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (-)
6-69676250-C-T		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
6-69676251-A-G		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Nov 24, 2023)
6-69676257-T-A		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Mar 01, 2023)
6-69676271-C-A		Methylmalonic aciduria and homocystinuria type cblF	Uncertain significance (Jun 27, 2022)
6-69676275-T-C		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Dec 11, 2023)
6-69676280-T-G		Methylmalonic aciduria and homocystinuria type cblF	Likely benign (Dec 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMBRD1	protein_coding	protein_coding	ENST00000370577	16	121310

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.03e-11	0.896	125553	0	195	125748	0.000776

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.257	272	284	0.957	0.0000142	3512
Missense in Polyphen		58	71.069	0.8161		859
Synonymous	0.559	91	98.0	0.928	0.00000486	1005
Loss of Function	1.88	21	32.6	0.644	0.00000164	406

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00181	0.00179
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000744	0.000739
European (Non-Finnish)	0.00116	0.00114
Middle Eastern	0.000109	0.000109
South Asian	0.000197	0.000196
Other	0.000658	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable lysosomal cobalamin transporter. Required to export cobalamin from lysosomes allowing its conversion to cofactors. {ECO:0000269|PubMed:19136951}.
• Disease: DISEASE: Methylmalonic aciduria and homocystinuria, cblF type (MAHCF) [MIM:277380]: An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). It is due to accumulation of free cobalamin in lysosomes, thus hindering its conversion to cofactors. Clinical features include developmental delay, stomatitis, glossitis, seizures and methylmalonic aciduria responsive to vitamin B12. {ECO:0000269|PubMed:19136951}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vitamin digestion and absorption - Homo sapiens (human);Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.919
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.54

Haploinsufficiency Scores

• pHI: 0.231
• hipred: N
• hipred_score: 0.333
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.132

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lmbrd1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; cellular phenotype

Gene ontology

• Biological process: cobalamin metabolic process;cobalamin transport;viral process
• Cellular component: lysosomal membrane;plasma membrane;membrane;integral component of membrane;clathrin-coated endocytic vesicle
• Molecular function: insulin receptor binding;cobalamin-transporting ATPase activity;cobalamin binding