LMBRD1
Basic information
Region (hg38): 6:69672757-69867236
Previous symbols: [ "C6orf209" ]
Links
Phenotypes
GenCC
Source:
- 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:
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
- Methylmalonic aciduria and homocystinuria type cblF (22 variants)
- Disorders of Intracellular Cobalamin Metabolism (1 variants)
- Cobalamin C disease (1 variants)
- not provided (1 variants)
- Inborn genetic diseases (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 | 95 | 98 | ||||
missense | 102 | 104 | ||||
nonsense | 10 | |||||
start loss | 0 | |||||
frameshift | 12 | 16 | ||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 17 | 17 | ||||
splice region | 1 | 1 | 34 | 2 | 38 | |
non coding | 17 | 123 | 36 | 176 | ||
Total | 21 | 22 | 120 | 219 | 39 |
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) | ||
6-69676215-T-A | Inborn genetic diseases | Uncertain significance (Mar 28, 2024) | ||
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) |
GnomAD
Source:
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:
- 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