LMF1

lipase maturation factor 1

Basic information

Region (hg38): 16:853633-981318

Previous symbols: [ "C16orf26", "TMEM112" ]

Links

ENSG00000103227 ∙ NCBI:64788 ∙ OMIM:611761 ∙ HGNC:14154 ∙ Uniprot:Q96S06 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lipase deficiency, combined (Strong), mode of inheritance: AR
• lipase deficiency, combined (Moderate), mode of inheritance: AR
• lipase deficiency, combined (Strong), mode of inheritance: AR
• lipase deficiency, combined (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined lipase deficiency	AR	Cardiovascular; Endocrine; Gastrointestinal	Individuals may present with severe hypertryglceridemia, with findings including gastrointestinal manifestations (abdominal pain, emesis, recurrent pancreatitis, hepatosplenomegaly), as well as eruptive xanthomata and lipemia retinalis, and dietary measures (fat restriction) and medical treatment (eg, gemfibrozil, omega-3 fatty acid supplementation) can be beneficial; Individuals may also manifest with diabetes mellitus, which can benefit from standard treatment (and which may also help with other manifestations)	Cardiovascular; Endocrine; Gastrointestinal	17994020; 19820022

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMF1 gene.

• Cardiovascular phenotype (290 variants)
• not provided (237 variants)
• Lipase deficiency, combined (30 variants)
• Inborn genetic diseases (29 variants)
• not specified (9 variants)
• LMF1-related condition (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				137	7	144
missense			184	14	10	208
nonsense	4	6				10
start loss						0
frameshift	1	3	1			5
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	1	1			3
splice region			4	4	2	10
non coding			3	40	43	86
Total	6	10	190	191	60

Highest pathogenic variant AF is 0.0000394

Variants in LMF1

This is a list of pathogenic ClinVar variants found in the LMF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-854236-C-T			Likely benign (Apr 20, 2019)
16-854301-G-T			Likely benign (Oct 01, 2018)
16-854358-G-T			Likely benign (Apr 21, 2019)
16-854395-C-T			Likely benign (Apr 20, 2019)
16-854538-G-A		Cardiovascular phenotype	Likely benign (Oct 11, 2021)
16-854540-G-A		Cardiovascular phenotype	Uncertain significance (Dec 03, 2021)
16-854542-C-A		Cardiovascular phenotype	Uncertain significance (May 02, 2022)
16-854544-G-A		Cardiovascular phenotype	Likely benign (Nov 24, 2022)
16-854547-C-T		Cardiovascular phenotype	Likely benign (Jun 17, 2020)
16-854548-A-C			Likely benign (May 05, 2023)
16-854551-G-C		Cardiovascular phenotype	Benign (Jan 26, 2024)
16-854559-A-G		Cardiovascular phenotype	Likely benign (Dec 31, 2022)
16-854561-G-A		Cardiovascular phenotype	Uncertain significance (Feb 04, 2022)
16-854563-T-C		Cardiovascular phenotype	Uncertain significance (Nov 07, 2022)
16-854574-G-C		Cardiovascular phenotype	Likely benign (Jan 30, 2022)
16-854585-C-T		Cardiovascular phenotype	Uncertain significance (Aug 28, 2023)
16-854591-G-C		Cardiovascular phenotype	Uncertain significance (Nov 10, 2023)
16-854598-C-T		Cardiovascular phenotype	Likely benign (Jun 22, 2021)
16-854599-G-C		Cardiovascular phenotype	Uncertain significance (Oct 06, 2021)
16-854616-G-A		Cardiovascular phenotype • LMF1-related disorder	Conflicting classifications of pathogenicity (Jun 07, 2023)
16-854625-C-T		Cardiovascular phenotype	Likely benign (Apr 22, 2021)
16-854626-C-T			Uncertain significance (Mar 14, 2022)
16-854627-G-T		Cardiovascular phenotype	Likely benign (Jan 19, 2023)
16-854628-C-A		Cardiovascular phenotype • Lipase deficiency, combined	Benign/Likely benign (Nov 27, 2023)
16-854630-C-T		Cardiovascular phenotype	Uncertain significance (Dec 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMF1	protein_coding	protein_coding	ENST00000262301	11	127685

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.14e-16	0.0251	124553	0	113	124666	0.000453

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.79	446	351	1.27	0.0000225	3630
Missense in Polyphen		170	139.91	1.2151		1431
Synonymous	-2.66	194	152	1.27	0.0000104	1140
Loss of Function	0.442	25	27.5	0.909	0.00000143	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000902	0.000889
Ashkenazi Jewish	0.00	0.00
East Asian	0.000671	0.000668
Finnish	0.000145	0.000139
European (Non-Finnish)	0.000451	0.000443
Middle Eastern	0.000671	0.000668
South Asian	0.000690	0.000686
Other	0.000906	0.000826

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the maturation of specific proteins in the endoplasmic reticulum. Required for maturation and transport of active lipoprotein lipase (LPL) through the secretory pathway. Each LMF1 molecule chaperones 50 or more molecules of LPL. {ECO:0000250|UniProtKB:Q3U3R4, ECO:0000269|PubMed:24909692}.
• Disease: DISEASE: Combined lipase deficiency (CLD) [MIM:246650]: Characterized by repeated episodes of pancreatitis, tuberous xanthomas and lipodystrophy and is caused by deficiency of both lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). {ECO:0000269|PubMed:17994020}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transport of small molecules;Assembly of active LPL and LIPC lipase complexes;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.865
• rvis_EVS: 1.23
• rvis_percentile_EVS: 93.26

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.229
• ghis: 0.477

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.444

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lmf1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype

Gene ontology

• Biological process: triglyceride metabolic process;endoplasmic reticulum to Golgi vesicle-mediated transport;protein secretion;protein glycosylation in Golgi;chylomicron remnant clearance;regulation of lipoprotein lipase activity;positive regulation of lipoprotein lipase activity;protein maturation;regulation of cholesterol metabolic process;regulation of triglyceride metabolic process
• Cellular component: endoplasmic reticulum membrane;Golgi apparatus;integral component of membrane