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

ENSG00000074582 ∙ NCBI:617 ∙ OMIM:603647 ∙ HGNC:1020 ∙ Uniprot:Q9Y276 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
• 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
• Leigh syndrome (Limited), mode of inheritance: AR
• Bjornstad syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 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	144	2	147
missense	3	16	62	3		84
nonsense	6	22				28
start loss	1	1				2
frameshift	10	28	1			39
inframe indel			5			5
splice donor/acceptor (+/-2bp)	2	12				14
splice region			2	20		22
non coding		2	10	31	8	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)
2-218659708-G-A		Mitochondrial complex III deficiency nuclear type 1 • Leigh syndrome • GRACILE syndrome • GRACILE syndrome;Pili torti-deafness syndrome;Mitochondrial complex III deficiency nuclear type 1	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)
2-218660069-A-G		Pili torti-deafness syndrome	Likely pathogenic (Oct 16, 2023)
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 classifications 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	Conflicting classifications of pathogenicity (Jun 18, 2023)
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)

GnomAD

Source: gnomAD

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: 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

	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