BCS1L
BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone, the group of Mitochondrial respiratory chain complex assembly factors|AAA ATPases
Basic information
Region (hg38): 2:218658763-218663443
Links
Phenotypes
GenCC
Source:
- Bjornstad syndrome (Strong), mode of inheritance: AR
- Leigh syndrome (Strong), mode of inheritance: AR
- GRACILE syndrome (Definitive), mode of inheritance: AR
- Bjornstad syndrome (Moderate), mode of inheritance: AR
- mitochondrial complex III deficiency nuclear type 1 (Strong), mode of inheritance: AR
- mitochondrial complex III deficiency (Supportive), mode of inheritance: AR
- Bjornstad syndrome (Supportive), mode of inheritance: AR
- GRACILE syndrome (Supportive), mode of inheritance: AR
- renal tubulopathy-encephalopathy-liver failure syndrome (Supportive), mode of inheritance: AR
- Leigh syndrome (Limited), mode of inheritance: AR
- Bjornstad syndrome (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Bjornstad syndrome; Mitochondrial complex III deficiency, nuclear type 1 | AR | Audiologic/Otolaryngologic; Biochemical | In Bjornstad syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial); In Mitochondrial complex III deficiency, nuclear, some treatment attempts (eg, with apotransferrin) have been reported, and treatment with "mitochondrial cocktail" type therapy may be beneficial | Audiologic/Otolaryngologic; Biochemical; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic; Renal | 9482441; 10654962; 7577396; 10654962; 11528392; 12215968; 12910490; 17314340; 17403714; 19162478; 19389488; 19508421; 20580947; 20518024; 20472482; 22277166; 22991165 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (311 variants)
- GRACILE syndrome (91 variants)
- Mitochondrial complex III deficiency nuclear type 1 (47 variants)
- not specified (25 variants)
- Leigh syndrome (24 variants)
- Inborn genetic diseases (10 variants)
- Pili torti-deafness syndrome (9 variants)
- Pili torti-deafness syndrome;Mitochondrial complex III deficiency nuclear type 1;GRACILE syndrome (9 variants)
- GRACILE syndrome;Pili torti-deafness syndrome;Mitochondrial complex III deficiency nuclear type 1 (7 variants)
- Pili torti-deafness syndrome;GRACILE syndrome;Mitochondrial complex III deficiency nuclear type 1 (7 variants)
- BCS1L-Related Disorders (5 variants)
- GRACILE syndrome;Mitochondrial complex III deficiency nuclear type 1;Pili torti-deafness syndrome (4 variants)
- Mitochondrial complex III deficiency nuclear type 1;GRACILE syndrome;Pili torti-deafness syndrome (3 variants)
- See cases (2 variants)
- Intellectual disability (2 variants)
- Mitochondrial complex III deficiency nuclear type 1;Pili torti-deafness syndrome;GRACILE syndrome (2 variants)
- Bjornstad syndrome with mild mitochondrial complex III deficiency (2 variants)
- Decreased activity of mitochondrial complex III (2 variants)
- Neonatal encephalopathy (1 variants)
- Severe global developmental delay;Seizure (1 variants)
- Microcephaly;Sparse hair;Movement disorder (1 variants)
- Movement disorder;Microcephaly;Sparse hair (1 variants)
- Leigh syndrome;Pili torti-deafness syndrome;GRACILE syndrome;Mitochondrial complex III deficiency nuclear type 1 (1 variants)
- Microcephaly;Sparse hair;Intellectual disability, severe;Movement disorder (1 variants)
- Movement disorder;Microcephaly;Sparse hair;Intellectual disability, severe (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCS1L gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 122 | 2 | 125 | ||
| missense | 10 | 19 | 65 | 15 | 1 | 110 |
| nonsense | 11 | 13 | 1 | 25 | ||
| start loss | 0 | |||||
| frameshift | 9 | 18 | 1 | 28 | ||
| inframe indel | 5 | 5 | ||||
| splice variant | 3 | 12 | 6 | 23 | 1 | 45 |
| non coding | 1 | 9 | 21 | 8 | 39 | |
| Total | 33 | 63 | 87 | 182 | 12 |
Highest pathogenic variant AF is 0.000394
Variants in BCS1L
This is a list of pathogenic ClinVar variants found in the BCS1L region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 2-218659583-G-A | Benign (Apr 02, 2019) | |||
| 2-218659708-G-A | Mitochondrial complex III deficiency nuclear type 1 • Leigh syndrome • GRACILE syndrome • Mitochondrial complex III deficiency nuclear type 1;Pili torti-deafness syndrome;GRACILE syndrome | Uncertain significance (Feb 02, 2022) | ||
| 2-218659740-G-T | GRACILE syndrome • Mitochondrial complex III deficiency nuclear type 1 • Leigh syndrome | Uncertain significance (Jan 13, 2018) | ||
| 2-218659744-G-A | GRACILE syndrome | Uncertain significance (Jan 23, 2018) | ||
| 2-218659744-G-T | GRACILE syndrome | Uncertain significance (Nov 01, 2017) | ||
| 2-218659745-T-G | GRACILE syndrome | Uncertain significance (Jan 08, 2018) | ||
| 2-218659750-G-C | Likely benign (Apr 23, 2018) | |||
| 2-218659756-A-G | not specified | Benign (Jul 06, 2011) | ||
| 2-218660025-C-T | not specified | Likely benign (Oct 02, 2017) | ||
| 2-218660123-G-C | GRACILE syndrome | Uncertain significance (Jan 28, 2022) | ||
| 2-218660131-C-G | GRACILE syndrome | Likely pathogenic (May 28, 2019) | ||
| 2-218660148-A-G | GRACILE syndrome • Mitochondrial complex III deficiency nuclear type 1 | Conflicting interpretations of pathogenicity (Jun 07, 2022) | ||
| 2-218660168-T-C | GRACILE syndrome • Mitochondrial complex III deficiency nuclear type 1 • Leigh syndrome | Uncertain significance (Jan 12, 2018) | ||
| 2-218660201-T-G | Mitochondrial complex III deficiency nuclear type 1 • GRACILE syndrome • Leigh syndrome | Uncertain significance (Jan 12, 2018) | ||
| 2-218660284-G-A | GRACILE syndrome | Benign (Jun 14, 2018) | ||
| 2-218660298-C-A | Likely benign (Jul 27, 2018) | |||
| 2-218660306-G-A | GRACILE syndrome | Benign (Jul 09, 2018) | ||
| 2-218660344-A-G | GRACILE syndrome | Likely benign (Jun 16, 2018) | ||
| 2-218660400-T-A | GRACILE syndrome | Uncertain significance (Jun 07, 2018) | ||
| 2-218660409-C-T | Likely benign (Jul 15, 2018) | |||
| 2-218660503-AC-A | Likely benign (Jun 19, 2018) | |||
| 2-218660549-A-G | Benign (Jul 09, 2018) | |||
| 2-218660612-C-T | Benign (Jun 14, 2018) | |||
| 2-218660859-A-G | Benign (Jun 23, 2018) | |||
| 2-218660927-C-G | Uncertain significance (Oct 14, 2016) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BCS1L | protein_coding | protein_coding | ENST00000431802 | 7 | 4680 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.70e-13 | 0.0982 | 125614 | 0 | 134 | 125748 | 0.000533 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.62 | 170 | 241 | 0.707 | 0.0000159 | 2705 |
| Missense in Polyphen | 62 | 106.85 | 0.58024 | 1144 | ||
| Synonymous | -0.481 | 100 | 94.1 | 1.06 | 0.00000574 | 890 |
| Loss of Function | 0.647 | 21 | 24.5 | 0.859 | 0.00000199 | 201 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00119 | 0.00119 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000381 | 0.000381 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000678 | 0.000677 |
| Middle Eastern | 0.000381 | 0.000381 |
| South Asian | 0.000523 | 0.000523 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Chaperone necessary for the assembly of mitochondrial respiratory chain complex III. Plays an important role in the maintenance of mitochondrial tubular networks, respiratory chain assembly and formation of the LETM1 complex. {ECO:0000269|PubMed:18628306}.;
- Disease
- DISEASE: Mitochondrial complex III deficiency, nuclear 1 (MC3DN1) [MIM:124000]: A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance. {ECO:0000269|PubMed:11528392, ECO:0000269|PubMed:12910490, ECO:0000269|PubMed:17314340, ECO:0000269|PubMed:17403714, ECO:0000269|PubMed:18628306, ECO:0000269|PubMed:19162478, ECO:0000269|PubMed:22991165}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bjoernstad syndrome (BJS) [MIM:262000]: An autosomal recessive disease characterized by congenital sensorineural hearing loss and twisted hairs (pili torti). Pili torti is a condition in which the hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair extremely brittle. {ECO:0000269|PubMed:17314340, ECO:0000269|PubMed:24172246}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Metabolism of proteins;Mitochondrial protein import
(Consensus)
Recessive Scores
- pRec
- 0.654
Intolerance Scores
- loftool
- 0.170
- rvis_EVS
- -0.62
- rvis_percentile_EVS
- 17.16
Haploinsufficiency Scores
- pHI
- 0.181
- hipred
- Y
- hipred_score
- 0.578
- ghis
- 0.596
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.917
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Bcs1l
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; renal/urinary system 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); reproductive system phenotype;
Gene ontology
- Biological process
- mitochondrion organization;mitochondrial respiratory chain complex I assembly;mitochondrial respiratory chain complex IV assembly;mitochondrial respiratory chain complex III assembly
- Cellular component
- mitochondrion;mitochondrial respiratory chain complex III;integral component of membrane
- Molecular function
- protein binding;ATP binding