Details for: LMF1

Gene ID: 64788

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: LMF1

Ensembl ID: ENSG00000103227

Description: lipase maturation factor 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 7.7
    rCSI 29.09%
    PRS 69.59
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 6.41
    rCSI 23.07%
    PRS 67.22
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 6.09
    rCSI 14.79%
    PRS 67.04
  • pro-B cell CL0000826
    CSI 5.18
    rCSI 4.29%
    PRS 87.42
  • pulmonary alveolar type 1 cell CL0002062
    CSI 5.1
    rCSI 29.39%
    PRS 81.75
  • regular ventricular cardiac myocyte CL0002131
    CSI 4.16
    rCSI 26.01%
    PRS 77.88
  • melanocyte CL0000148
    CSI 4.09
    rCSI 3.03%
    PRS 79.97
  • neural crest cell CL0011012
    CSI 3.85
    rCSI 3.04%
    PRS 75.94
  • fibroblast of cardiac tissue CL0002548
    CSI 3.67
    rCSI 17.58%
    PRS 85.45
  • vascular leptomeningeal cell CL4023051
    CSI 3.54
    rCSI 6.2%
    PRS 80.19
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.5
    rCSI 6.18%
    PRS 68.75
  • Kupffer cell CL0000091
    CSI 3.42
    rCSI 7.81%
    PRS 86.25
  • Mueller cell CL0000636
    CSI 3.16
    rCSI 7.22%
    PRS 77.56
  • cardiac muscle cell CL0000746
    CSI 3.09
    rCSI 4.44%
    PRS 76.09
  • pancreatic A cell CL0000171
    CSI 3
    rCSI 3.14%
    PRS 88.04
  • precursor B cell CL0000817
    CSI 2.86
    rCSI 2.5%
    PRS 90.77
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.85
    rCSI 3.54%
    PRS 67.15
  • mature astrocyte CL0002627
    CSI 2.8
    rCSI 11.89%
    PRS 78.23
  • chondrocyte CL0000138
    CSI 2.79
    rCSI 4.43%
    PRS 79.16
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.77
    rCSI 7.21%
    PRS 86.46
  • lung ciliated cell CL1000271
    CSI 2.76
    rCSI 3.19%
    PRS 78.64
  • mucus secreting cell CL0000319
    CSI 2.74
    rCSI 4.35%
    PRS 91.67
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.72
    rCSI 3.5%
    PRS 70.42
  • pancreatic D cell CL0000173
    CSI 2.7
    rCSI 2.66%
    PRS 87.23
  • respiratory suprabasal cell CL4033048
    CSI 2.66
    rCSI 3.41%
    PRS 87.79
  • retinal pigment epithelial cell CL0002586
    CSI 2.61
    rCSI 5.18%
    PRS 81.34
  • bronchus fibroblast of lung CL2000093
    CSI 2.6
    rCSI 2.12%
    PRS 84.5
  • ciliated epithelial cell CL0000067
    CSI 2.58
    rCSI 2.27%
    PRS 75.45
  • myeloid leukocyte CL0000766
    CSI 2.56
    rCSI 2.36%
    PRS 86.48
  • cerebral cortex endothelial cell CL1001602
    CSI 2.43
    rCSI 4.2%
    PRS 78
  • inhibitory interneuron CL0000498
    CSI 2.43
    rCSI 5.6%
    PRS 74.46
  • hepatic stellate cell CL0000632
    CSI 2.41
    rCSI 9.03%
    PRS 78.9
  • alveolar adventitial fibroblast CL4028006
    CSI 2.35
    rCSI 3.71%
    PRS 86.28
  • blood vessel endothelial cell CL0000071
    CSI 2.32
    rCSI 4.82%
    PRS 82.53
  • IgG plasma cell CL0000985
    CSI 2.32
    rCSI 2.77%
    PRS 92.3
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.29
    rCSI 3.24%
    PRS 82.53
  • regular atrial cardiac myocyte CL0002129
    CSI 2.23
    rCSI 7.16%
    PRS 81.97
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.06
    rCSI 2.46%
    PRS 69.34
  • amacrine cell CL0000561
    CSI 2
    rCSI 5.79%
    PRS 75.56
  • small pre-B-II cell CL0000954
    CSI 2
    rCSI 1.92%
    PRS 94.64
  • stem cell CL0000034
    CSI 1.98
    rCSI 1.9%
    PRS 79.99
  • cardiac endothelial cell CL0010008
    CSI 1.88
    rCSI 7.6%
    PRS 85.63
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.88
    rCSI 1.45%
    PRS 88.51
  • choroid plexus epithelial cell CL0000706
    CSI 1.79
    rCSI 2.94%
    PRS 76.21
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.77
    rCSI 4.57%
    PRS 81.52
  • lung secretory cell CL1000272
    CSI 1.75
    rCSI 4.33%
    PRS 85.72
  • renal beta-intercalated cell CL0002201
    CSI 1.64
    rCSI 3.91%
    PRS 85.07
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.63
    rCSI 2.73%
    PRS 69.18
  • late pro-B cell CL0002048
    CSI 1.61
    rCSI 4.04%
    PRS 94.62
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 1.57
    rCSI 6.12%
    PRS 96.13
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.56
    rCSI 37.65%
    PRS 67.52
  • direct pathway medium spiny neuron CL4023026
    CSI 1.54
    rCSI 36.98%
    PRS 67.08
  • parietal epithelial cell CL1000452
    CSI 1.54
    rCSI 4.13%
    PRS 78.3
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.53
    rCSI 3.43%
    PRS 70.17
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.49
    rCSI 2.4%
    PRS 70.62
  • renal principal cell CL0005009
    CSI 1.48
    rCSI 3.85%
    PRS 84.98
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.48
    rCSI 3.99%
    PRS 88.58
  • epithelial cell of proximal tubule CL0002306
    CSI 1.41
    rCSI 3.44%
    PRS 78.05
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.3
    rCSI 3.29%
    PRS 77.16
  • retinal ganglion cell CL0000740
    CSI 1.26
    rCSI 2.79%
    PRS 72.48
  • central nervous system neuron CL2000029
    CSI 1.23
    rCSI 9.07%
    PRS 74.21
  • GABAergic amacrine cell CL4030027
    CSI 1.19
    rCSI 4.09%
    PRS 71.63
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.08
    rCSI 6.34%
    PRS 69.72
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1
    rCSI 2.4%
    PRS 73.05
  • dopaminergic neuron CL0000700
    CSI 0.92
    rCSI 5.21%
    PRS 72.49
  • podocyte CL0000653
    CSI 0.83
    rCSI 3.71%
    PRS 86.02
  • blood vessel smooth muscle cell CL0019018
    CSI 0.74
    rCSI 5.98%
    PRS 80.59
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.63
    rCSI 1.97%
    PRS 72.86
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.51
    rCSI 1.59%
    PRS 70.73
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.42
    rCSI 4.42%
    PRS 81.44
  • acinar cell of salivary gland CL0002623
    CSI 0.17
    rCSI 3.94%
    PRS 93.02

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Analyzed for its expression specificity (CSI Z-Score), lipase maturation factor 1, or [LMF1](/details-gene/64788), does not emerge as a distinguishing marker for any single cell type. Instead, its broad expression across diverse cell lineages—including neuronal, myeloid, and mesenchymal cells—suggests it performs a ubiquitous and fundamental housekeeping function. This is consistent with its established role as an endoplasmic reticulum-resident chaperone essential for the maturation and activity of several key lipases involved in systemic triglyceride metabolism. Mutations in [LMF1](/details-gene/64788) are causally linked to combined lipase deficiency and severe hypertriglyceridemia ([153245](https://omim.org/entry/246650)), as reported by Péterfy et al. (PubMed: [17994020](https://pubmed.ncbi.nlm.nih.gov/17994020/), DOI: [10.1038/ng.2007.24](https://doi.org/10.1038/ng.2007.24)). ## Cellular Roles and Expression Landscape The expression profile of [LMF1](/details-gene/64788), when evaluated for cell-type specificity, reveals a notable lack of it. In the **Overall** context, the CSI (Z-SCORE) is 0.00 with non-significant p-values across all top-listed cell types. This pattern strongly indicates that while [LMF1](/details-gene/64788) is expressed in many cells, its expression level is not uniquely elevated in any particular one to serve as a defining marker. Despite the lack of specificity, the data show its presence in a wide variety of functionally distinct cells. These include neuronal subtypes like [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041), immune cells such as [Kupffer cell](/details-cell/CL0000091), and structural cells like [fibroblast of cardiac tissue](/details-cell/CL0002548). The Percentile Rank Scores (PRS) are moderately high in several of these cell types, such as [pancreatic A cell](/details-cell/CL0000171) (PRS: 88.04%) and [pro-B cell](/details-cell/CL0000826) (PRS: 87.42%), suggesting that while its expression is not specific, it is more abundant in these cells compared to the transcriptome-wide median. This widespread, non-specific expression pattern is highly consistent with a fundamental housekeeping role, particularly one involving a core metabolic process required by most cells. ## Pathways and Molecular Function The functional annotations for [LMF1](/details-gene/64788) align perfectly with its observed broad expression and lack of cell-type specificity. It is an integral component of the [endoplasmic reticulum membrane](/ontology/GO:0005789) and is central to [protein maturation](/ontology/GO:0051604), a fundamental process occurring in virtually all eukaryotic cells. Studies have clarified that LMF1 is a chaperone protein required for the correct folding and activation of lipases within the endoplasmic reticulum (PubMed: [19783858](https://pubmed.ncbi.nlm.nih.gov/19783858/), DOI: [10.1074/jbc.m109.049395](https://doi.org/10.1074/jbc.m109.049395)). Specifically, it participates in Reactome pathways essential for lipid homeostasis, including the '[Assembly of active lpl and lipc lipase complexes](/reactome/R-HSA-8963889)' and the broader '[Plasma lipoprotein assembly, remodeling, and clearance](/reactome/R-HSA-174824)'. These pathways manage the metabolism of triglycerides, a critical energy source and signaling molecule for diverse tissues. The necessity of this function in many different cell types, from energy-demanding [cardiac muscle cell](/details-cell/CL0000746)s to metabolically active [Kupffer cell](/details-cell/CL0000091)s, explains why [LMF1](/details-gene/64788) is expressed broadly rather than being restricted to a specific cellular context. ## Research Directions The ubiquitous expression of [LMF1](/details-gene/64788) underscores its fundamental biological importance, but it also raises questions about potential cell-type-specific consequences of its dysfunction beyond systemic hypertriglyceridemia. The absence of comparative data (e.g., Disease vs. Healthy) or information on variable expression limits the scope of analysis, but the existing profile allows for the formulation of several hypotheses. **Testable Hypotheses:** 1. **Hypothesis:** Although expressed broadly, the functional dependency on [LMF1](/details-gene/64788) is proportional to a cell's reliance on extracellular lipid uptake. Cells with high lipid flux, such as [Kupffer cell](/details-cell/CL0000091)s or [cardiac muscle cell](/details-cell/CL0000746)s, will be more susceptible to lipotoxicity following [LMF1](/details-gene/64788) disruption compared to cells with lower lipid turnover, like certain neuronal subtypes. * **Experimental Approach:** Utilize CRISPR/Cas9 or siRNA to selectively knock down [LMF1](/details-gene/64788) in primary cultures of human Kupffer cells, cardiomyocytes, and cortical neurons. Expose the cultures to high levels of fatty acids and assess markers of cellular stress, apoptosis, and intracellular lipid accumulation via Bodipy staining and Seahorse metabolic analysis. 2. **Hypothesis:** In the central nervous system, [LMF1](/details-gene/64788) expression in glutamatergic neurons (e.g., [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041)) is essential for maintaining local lipid homeostasis required for synaptic membrane integrity and neurotransmission. Its deficiency may contribute to synaptic vulnerability in neurodegenerative contexts. * **Experimental Approach:** Generate a neuron-specific `Lmf1` conditional knockout mouse model (e.g., using a Camk2a-Cre driver). Characterize synaptic structure and function using electrophysiology (mEPSCs/mIPSCs) and immunohistochemistry for synaptic markers (e.g., PSD-95, Synaptophysin) at baseline and in response to metabolic or excitotoxic stress. 3. **Hypothesis:** The expression of [LMF1](/details-gene/64788) in [fibroblast of cardiac tissue](/details-cell/CL0002548) is not passive but plays an active role in regulating the cardiac extracellular matrix and paracrine signaling in response to local lipid availability. Dysfunctional [LMF1](/details-gene/64788) in cardiac fibroblasts may promote a pro-fibrotic phenotype in conditions of cardiac steatosis. * **Experimental Approach:** Isolate primary cardiac fibroblasts from wild-type mice and knock down `Lmf1` expression using lentiviral shRNA. Treat these cells with palmitate to mimic a lipotoxic environment and analyze the expression of pro-fibrotic genes (e.g., `Col1a1`, `Acta2`, `Tgf-β1`) via RT-qPCR and assess collagen secretion using a Sirius Red assay. **Therapeutic Potential:** Given that loss-of-function mutations in [LMF1](/details-gene/64788) cause a severe monogenic lipid disorder, the primary therapeutic avenue is corrective. Strategies such as AAV-mediated gene therapy aimed at restoring [LMF1](/details-gene/64788) expression, particularly in the liver, could offer a causal treatment for combined lipase deficiency ([153245](https://omim.org/entry/246650)). Conversely, inhibiting [LMF1](/details-gene/64788) is unlikely to be a viable therapeutic strategy for any condition due to its essential, housekeeping role in lipid metabolism across numerous tissues, which would likely result in unacceptable systemic toxicity.

Genular Protein ID: 1683678379

Symbol: LMF1_HUMAN

Name: Lipase maturation factor 1

UniProtKB Accession Codes:

Q96S06 B3KS80 Q68CJ3 Q96FJ4 Q9H6G4 Q9H9K7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 16 Ensembl 2 ExpressionAtlas 1 GO 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 STRING 1 SignaLink 1 TreeFam 1 UCSC 2 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 11157797

Title: Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16.

PubMed ID: 11157797

DOI: 10.1093/hmg/10.4.339

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 15221005

Title: Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.

PubMed ID: 15221005

DOI: 10.1038/sj.onc.1207782

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17994020

Title: Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia.

PubMed ID: 17994020

DOI: 10.1038/ng.2007.24

PubMed ID: 19783858

Title: Lipase maturation factor LMF1, membrane topology and interaction with lipase proteins in the endoplasmic reticulum.

PubMed ID: 19783858

DOI: 10.1074/jbc.m109.049395

PubMed ID: 31399538

Title:

PubMed ID: 31399538

DOI: 10.1074/jbc.w119.010212

PubMed ID: 24909692

Title: Purification, cellular levels, and functional domains of lipase maturation factor 1.

PubMed ID: 24909692

DOI: 10.1016/j.bbrc.2014.05.136

Sequence Information:

  • Length: 567
  • Mass: 64873
  • Checksum: 6D4C80741D1DD0D5
  • Sequence:
    • MRPDSPTMAA PAESLRRRKT GYSDPEPESP PAPGRGPAGS PAHLHTGTFW LTRIVLLKAL 
AFVYFVAFLV AFHQNKQLIG DRGLLPCRVF LKNFQQYFQD RTSWEVFSYM PTILWLMDWS 
DMNSNLDLLA LLGLGISSFV LITGCANMLL MAALWGLYMS LVNVGHVWYS FGWESQLLET 
GFLGIFLCPL WTLSRLPQHT PTSRIVLWGF RWLIFRIMLG AGLIKIRGDR CWRDLTCMDF 
HYETQPMPNP VAYYLHHSPW WFHRFETLSN HFIELLVPFF LFLGRRACII HGVLQILFQA 
VLIVSGNLSF LNWLTMVPSL ACFDDATLGF LFPSGPGSLK DRVLQMQRDI RGARPEPRFG 
SVVRRAANVS LGVLLAWLSV PVVLNLLSSR QVMNTHFNSL HIVNTYGAFG SITKERAEVI 
LQGTASSNAS APDAMWEDYE FKCKPGDPSR RPCLISPYHY RLDWLMWFAA FQTYEHNDWI 
IHLAGKLLAS DAEALSLLAH NPFAGRPPPR WVRGEHYRYK FSRPGGRHAA EGKWWVRKRI 
GAYFPPLSLE ELRPYFRDRG WPLPGPL