LMF2

Chr 22

lipase maturation factor 2

Also known as: TMEM112B, TMEM153

NCBI Gene: 91289 ENSG00000100258 UniProt: Q9BU23

LMF2 encodes a protein involved in the maturation of specific proteins in the endoplasmic reticulum, particularly required for maturation and transport of lipoprotein lipase through the secretory pathway. Mutations cause lipoprotein lipase deficiency with severe hypertriglyceridemia, inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in protein maturation. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.94

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.94LOEUF

pLI 0.000

Z-score -3.80

OE 1.68 (1.36–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.52Z-score

OE missense 1.34 (1.25–1.44)

577 obs / 429.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.68 (1.36–1.94)

0≤0.351.4

Missense OE?1.34 (1.25–1.44)

0≤0.61.4

Synonymous OE?1.64

0≤1.21.6

LoF obs/exp: 61 / 36.3Missense obs/exp: 577 / 429.8Syn Z: -7.08

Background carrier burden — how many people carry a rare variant somewhere in LMF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 32

1,317 rare PASS variants

Rare truncating (LoF)

1 in 350

258 rare PASS variants

Rare synonymous (reference)

1 in 39

683 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LMF2. 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 43	1 in 550
South Asian	~43k	1 in 28	1 in 310
Remaining (unassigned)	~30k	1 in 24	1 in 300
European (Finnish)	~27k	1 in 120	1 in 1,400
Admixed American	~22k	1 in 29	1 in 280
African / African American	~21k	1 in 30	1 in 230
East Asian	~20k	1 in 37	1 in 230
Ashkenazi Jewish	~13k	1 in 320	1 in 1,800
Middle Eastern	~2,884	1 in 37	1 in 240

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 14 coding exons well covered in gnomAD exomes. Genomes: 13 of 14 (exon 12 below).? see exons ↓