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: 4170 ENSG00000143384 UniProt: Q07820 OMIM: 159552

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

274

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in MCL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 96

592 rare PASS variants

Rare truncating (LoF)

1 in 3,600

30 rare PASS variants

Rare synonymous (reference)

1 in 300

240 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MCL1. 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 120	1 in 3,700
South Asian	~43k	1 in 69	1 in 1,300
Remaining (unassigned)	~30k	1 in 100	≈ 1 in 15,000
European (Finnish)	~27k	1 in 600	≈ 1 in 25,000
Admixed American	~22k	1 in 110	≈ 1 in 11,000
African / African American	~21k	1 in 120	1 in 2,500
East Asian	~20k	1 in 130	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 460	none seen
Middle Eastern	~2,884	1 in 280	≈ 1 in 2,900

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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓