BCS1L

Chr 2AR

BCS1 ubiquinol-cytochrome c reductase complex chaperone

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

NCBI Gene: 617ENSG00000074582UniProt: Q9Y276

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]

Primary Disease Associations & Inheritance

Bjornstad syndromeMIM #262000
AR
GRACILE syndromeMIM #603358
AR
Mitochondrial complex III deficiency, nuclear type 1MIM #124000
AR
UniProtBjoernstad syndrome
618
ClinVar variants
162
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BCS1L
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
162 Pathogenic / Likely Pathogenic· 146 VUS of 618 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.62Z-score
OE missense 0.71 (0.62–0.80)
170 obs / 240.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.86 (0.61–1.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.62–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 21 / 24.5Missense obs/exp: 170 / 240.5Syn Z: -0.48

ClinVar Variant Classifications

618 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic98
VUS146
Likely Benign266
Benign11
Conflicting33
64
Pathogenic
98
Likely Pathogenic
146
VUS
266
Likely Benign
11
Benign
33
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
11
36
0
64
Likely Pathogenic
41
26
30
1
98
VUS
6
117
18
5
146
Likely Benign
0
5
83
178
266
Benign
1
0
8
2
11
Conflicting
—33
Total65159175186618

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BCS1L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

BCS1L-related Bjornstad syndrome

limited
ADUndeterminedAltered Gene Product Structure
SkinEar
G2P ↗

BCS1L-related Gracile syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Bjornstad syndrome

MIM #262000

Molecular basis of disorder known

Autosomal recessive

GRACILE syndrome

MIM #603358

Molecular basis of disorder known

Autosomal recessive

Mitochondrial complex III deficiency, nuclear type 1

MIM #124000

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — BCS1L
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical spectrum of BCS1L Mitopathies and their underlying structural relationships.
Baker RA et al.·Am J Med Genet A
2019Case report
BCS1L-Associated Disease: 5'-UTR Variant Shifts the Phenotype Towards Axonal Neuropathy.
Orbach R et al.·Ann Clin Transl Neurol
2025Case report
Uncovering a Novel Pathogenic Mechanism of BCS1L in Mitochondrial Disorders: Insights from Functional Studies on the c.38A>G Variant.
Capaci V et al.·Int J Mol Sci
2025Case report
Identification of two novel variants of BCS1L gene in a patient with classical GRACILE syndrome.
Guo W et al.·Nephrology (Carlton)
2022
Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease.
Hikmat O et al.·Ann Clin Transl Neurol
2021
Clinical and biochemical features associated with BCS1L mutation.
Al-Owain M et al.·J Inherit Metab Dis
2013
Modelling of BCS1L-related human mitochondrial disease in Drosophila melanogaster.
Brischigliaro M et al.·J Mol Med (Berl)
2021Functional
BCS1L mutations produce Fanconi syndrome with developmental disability.
Kanako KI et al.·J Hum Genet
2022
Possible Bioenergetic Biomarker for Chronic Cancer-Related Fatigue.
Hsiao CP et al.·Nurs Res
2021
Clinical and diagnostic characteristics of complex III mitopathy due to novel BCS1L gene mutation in a Saudi patient.
Al Qurashi M et al.·BMC Med Genomics
2022Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools