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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

ENSG00000074582NCBI:617OMIM:603647HGNC:1020Uniprot:Q9Y276AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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
  • Bjornstad syndrome (Strong), mode of inheritance: AR
  • GRACILE syndrome (Strong), mode of inheritance: AR
  • mitochondrial complex III deficiency nuclear type 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Bjornstad syndrome; Mitochondrial complex III deficiency, nuclear type 1ARAudiologic/Otolaryngologic; BiochemicalIn 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 beneficialAudiologic/Otolaryngologic; Biochemical; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic; Renal9482441; 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 ClinVar and linked to the BCS1L gene.

  • not provided (349 variants)
  • GRACILE syndrome (90 variants)
  • Pili torti-deafness syndrome (55 variants)
  • Mitochondrial complex III deficiency nuclear type 1 (42 variants)
  • not specified (27 variants)
  • Leigh syndrome (24 variants)
  • Inborn genetic diseases (12 variants)
  • GRACILE syndrome;Mitochondrial complex III deficiency nuclear type 1;Pili torti-deafness syndrome (8 variants)
  • Pili torti-deafness syndrome;Mitochondrial complex III deficiency nuclear type 1;GRACILE syndrome (8 variants)
  • GRACILE syndrome;Pili torti-deafness syndrome;Mitochondrial complex III deficiency nuclear type 1 (6 variants)
  • BCS1L-Related Disorders (5 variants)
  • Mitochondrial complex III deficiency nuclear type 1;GRACILE syndrome;Pili torti-deafness syndrome (5 variants)
  • Mitochondrial complex III deficiency nuclear type 1;Pili torti-deafness syndrome;GRACILE syndrome (4 variants)
  • BCS1L-related condition (2 variants)
  • Microcephaly;Sparse hair;Movement disorder;Intellectual disability, severe (2 variants)
  • Microcephaly;Sparse hair;Movement disorder (2 variants)
  • Intellectual disability (2 variants)
  • Decreased activity of mitochondrial complex III (2 variants)
  • Neonatal encephalopathy (1 variants)
  • Mitochondrial complex III deficiency nuclear type 1;Leigh syndrome;GRACILE syndrome;Pili torti-deafness syndrome (1 variants)
  • Severe global developmental delay;Seizure (1 variants)
  • See cases (1 variants)
  • Bjornstad syndrome with mild mitochondrial complex III deficiency (1 variants)
  • Pili torti-deafness syndrome;GRACILE syndrome;Mitochondrial complex III deficiency nuclear type 1 (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.

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
1
clinvar
144
clinvar
2
clinvar
147
missense
3
clinvar
16
clinvar
62
clinvar
3
clinvar
84
nonsense
6
clinvar
22
clinvar
28
start loss
1
clinvar
1
clinvar
2
frameshift
10
clinvar
28
clinvar
1
clinvar
39
inframe indel
5
clinvar
5
splice donor/acceptor (+/-2bp)
2
clinvar
12
clinvar
14
splice region
2
20
22
non coding
2
clinvar
10
clinvar
31
clinvar
8
clinvar
51
Total 22 81 79 178 10

Highest pathogenic variant AF is 0.000394

Variants in BCS1L

This is a list of pathogenic ClinVar variants found in the BCS1L region.

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

Position Type Phenotype Significance ClinVar
2-218659583-G-A Benign (Apr 02, 2019)1262585
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)898620
2-218659740-G-T GRACILE syndrome • Mitochondrial complex III deficiency nuclear type 1 • Leigh syndrome Uncertain significance (Jan 13, 2018)334352
2-218659744-G-A GRACILE syndrome Uncertain significance (Jan 23, 2018)556251
2-218659744-G-T GRACILE syndrome Uncertain significance (Nov 01, 2017)554713
2-218659745-T-G GRACILE syndrome Uncertain significance (Jan 08, 2018)556020
2-218659750-G-C Likely benign (Apr 23, 2018)668251
2-218659756-A-G not specified Benign (Jul 06, 2011)136506
2-218660025-C-T not specified Likely benign (Oct 02, 2017)512097
2-218660069-A-G Pili torti-deafness syndrome Likely pathogenic (Oct 16, 2023)2680147
2-218660123-G-C GRACILE syndrome Uncertain significance (Jan 28, 2022)1683618
2-218660131-C-G GRACILE syndrome Likely pathogenic (May 28, 2019)801896
2-218660148-A-G GRACILE syndrome • Mitochondrial complex III deficiency nuclear type 1 Conflicting classifications of pathogenicity (Jun 07, 2022)553134
2-218660168-T-C GRACILE syndrome • Mitochondrial complex III deficiency nuclear type 1 • Leigh syndrome Uncertain significance (Jan 12, 2018)334353
2-218660201-T-G Mitochondrial complex III deficiency nuclear type 1 • GRACILE syndrome • Leigh syndrome Uncertain significance (Jan 12, 2018)334354
2-218660284-G-A GRACILE syndrome Benign (Jun 14, 2018)673726
2-218660298-C-A Likely benign (Jul 27, 2018)1209025
2-218660306-G-A GRACILE syndrome Benign (Jul 09, 2018)1259989
2-218660344-A-G GRACILE syndrome Likely benign (Jun 16, 2018)675506
2-218660400-T-A GRACILE syndrome Conflicting classifications of pathogenicity (Jun 18, 2023)56411
2-218660409-C-T Likely benign (Jul 15, 2018)559366
2-218660503-AC-A Likely benign (Jun 19, 2018)676726
2-218660549-A-G Benign (Jul 09, 2018)1239390
2-218660612-C-T Benign (Jun 14, 2018)669695
2-218660859-A-G Benign (Jun 23, 2018)1179749

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BCS1Lprotein_codingprotein_codingENST00000431802 74680
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
4.70e-130.098212561401341257480.000533
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.621702410.7070.00001592705
Missense in Polyphen62106.850.580241144
Synonymous-0.48110094.11.060.00000574890
Loss of Function0.6472124.50.8590.00000199201

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001190.00119
Ashkenazi Jewish0.000.00
East Asian0.0003810.000381
Finnish0.00009240.0000924
European (Non-Finnish)0.0006780.000677
Middle Eastern0.0003810.000381
South Asian0.0005230.000523
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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