BCL2L1

Chr 20

BCL2 like 1

Also known as: BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52

This protein functions as a potent inhibitor of cell death by blocking mitochondrial voltage-dependent anion channels and preventing caspase activation. Mutations cause a severe early-onset neurological disorder characterized by intellectual disability, seizures, and microcephaly, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.

Summary from RefSeq, UniProt
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1
Active trials
105
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
0.34
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryBCL2L1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 18 VUS of 43 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — BCL2L1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.937
Z-score 2.74
OE 0.00 (0.000.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.62Z-score
OE missense 0.62 (0.530.74)
91 obs / 146.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.34)
00.351.4
Missense OE0.62 (0.530.74)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 0 / 8.8Missense obs/exp: 91 / 146.1Syn Z: 0.55
DN
0.4090th %ile
GOF
0.5563th %ile
LOF
0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.34

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

43 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic6
VUS18
Likely Benign6
10
Pathogenic
6
Likely Pathogenic
18
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
6
0
6
VUS
0
8
10
0
18
Likely Benign
0
0
4
2
6
Benign
0
0
0
0
0
Total0830240

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

View in ClinVar →

Protein Context — Lollipop Plot

BCL2L1 · protein map & ClinVar variants

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

Clinical Literature
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