MCL1

Chr 1

MCL1 apoptosis regulator, BCL2 family member

Also known as: BCL2L3, EAT, MCL1-ES, MCL1L, MCL1S, Mcl-1, TM, bcl2-L-3

NCBI Gene: 4170ENSG00000143384UniProt: Q07820

This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.29
Clinical Summary— MCL1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
26 VUS of 42 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.29LOEUF
pLI 0.963
Z-score 2.97
OE 0.00 (0.00–0.29)
Highly constrained

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

Missense Constraint?
-0.36Z-score
OE missense 1.07 (0.96–1.20)
208 obs / 193.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.29)
0≤0.351.4
Missense OE?1.07 (0.96–1.20)
0≤0.61.4
Synonymous OE?1.07
0≤1.21.6
LoF obs/exp: 0 / 10.3Missense obs/exp: 208 / 193.7Syn Z: -0.49

This gene — mechanism propensity

DN
0.3793th %ile
GOF
0.5562th %ile
LOF
0.65top 25%

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

LOFprediction above median · LOEUF 0.29

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

42 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26
Likely Benign4
Benign3
26
VUS
4
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
26
0
0
26
Likely Benign
0
4
0
0
4
Benign
0
1
1
1
3
Total0311133

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap MCL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MCL1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients