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…

MultiplemechanismLOEUF 1.94

Clinical Summary— LMF2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

186 VUS of 226 total submissions

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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

This gene — mechanism propensity

0.6453th %ile

GOF

0.6637th %ile

LOF

0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

226 submitted variants in ClinVar

ClinVar

Classification Summary

VUS186

Likely Benign15

186

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	186	0	186
Likely Benign	11	4	15
Benign	0	0	0
Total	197	4	201

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

View in ClinVar →

146 pathogenic / likely-pathogenic (of 166) ClinVar copy-number / structural variants overlap LMF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →