BCS1L

Chr 2

BCS1 ubiquinol-cytochrome c reductase complex chaperone

Also known as: BCS, BCS1, BJS, FLNMS, GRACILE, Hs.6719, MC3DN1, PTD

NCBI Gene: 617 ENSG00000074582 UniProt: Q9Y276

The protein is essential for assembly of mitochondrial respiratory chain complex III. Autosomal recessive mutations cause mitochondrial complex III deficiency, GRACILE syndrome (growth restriction, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death), and Bjornstad syndrome. The pathogenic mechanism involves loss of function leading to defective complex III assembly and impaired cellular respiration.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a homolog of the S. cerevisiae bcs1 protein which is involved in the assembly of complex III of the mitochondrial respiratory chain. The encoded protein does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. Mutations in this gene are associated with mitochondrial complex III deficiency and the GRACILE syndrome. Several alternatively spliced transcripts encoding two different isoforms have been described. [provided by RefSeq, Jan 2016]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGRACILE syndrome

UniProtMitochondrial complex III deficiency, nuclear type 1

UniProtBjoernstad syndrome

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · mitochondrial disease · AR · ClinGen 2024
Definitive · Bjornstad syndrome · AR · ClinGen 2018
Definitive · GRACILE syndrome · AR · G2P
Definitive · mitochondrial complex III deficiency nuclear type 1 · AR · Natera
Limited · Leigh syndrome · AR · ClinGen 2019 — not for standalone diagnostic reporting

+2 more curated pairs

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.24

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — BCS1L

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.000

Z-score 0.65

OE 0.86 (0.61–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.62Z-score

OE missense 0.71 (0.62–0.80)

170 obs / 240.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.61–1.24)

0≤0.351.4

Missense OE?0.71 (0.62–0.80)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 21 / 24.5Missense obs/exp: 170 / 240.5Syn Z: -0.48

Background carrier burden — how many people carry a rare variant somewhere in BCS1L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

436 rare PASS variants

Rare truncating (LoF)

1 in 810

97 rare PASS variants

Rare synonymous (reference)

1 in 210

198 rare PASS variants

Rare missense and truncating variants are carried at similar rates in BCS1L; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 220	1 in 780
South Asian	~43k	1 in 100	1 in 580
Remaining (unassigned)	~30k	1 in 140	1 in 940
European (Finnish)	~27k	1 in 310	1 in 1,700
Admixed American	~22k	1 in 130	1 in 680
African / African American	~21k	1 in 160	1 in 1,300
East Asian	~20k	1 in 160	1 in 1,700
Ashkenazi Jewish	~13k	1 in 2,200	none seen
Middle Eastern	~2,884	1 in 180	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓