MGLL

protein-coding

monoglyceride lipase, the group of Lipases

Gene summary

This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

MANE transcript

NM_007283.7

Inheritance

—

ClinVar variants

U:31B:10

Top phenotype

MGLL-related disorder

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr3:127,689,062-128,052,190

External References & Databases

Ensembl (ENSG00000074416)

Transcript & Mutation Effects

hg38 • Region Span ~363.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MGLL variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 32

MGLL-related disorderTotal: 9

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007283.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	3 clinvar	4
missense			31 clinvar	5 clinvar	1 clinvar	37
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	31	6	4	41

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007283.7	RefSeq	NP_009214.1	8	MANE Select
ENST00000265052.10	Ensembl	ENSP00000265052.5	8	MANE Select
NM_001003794.3	RefSeq	NP_001003794.1	7	Standard
NM_001256585.2	RefSeq	NP_001243514.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of lipolysis in adipocytes - Homo sapiens (human)
Glycerolipid metabolism - Homo sapiens (human)
Retrograde endocannabinoid signaling - Homo sapiens (human)
Thermogenesis - Homo sapiens (human)
Lipid storage and perilipins in skeletal muscle

Biological Process

lipid metabolic process
fatty acid biosynthetic process
inflammatory response
regulation of signal transduction
arachidonic acid metabolic process

Molecular Function

lysophospholipase activity
protein homodimerization activity
acylglycerol lipase activity

Cellular Component

nucleoplasm
endoplasmic reticulum membrane
cytosol
plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265052
Coding exons: 8
Length: 134143
Individuals with no LoFs: 124790
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124795
p: 0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	148	189	0.782	0.0000119	2024
Missense (PolyPhen)		26	50.386	0.51601		552
Synonymous	0.492	75	80.6	0.930	0.00000579	648
Loss of Function	2.10	5	13.2	0.378	5.66e-7	160

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (By similarity). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth (PubMed:20079333). {ECO:0000250|UniProtKB:O35678, ECO:0000269|PubMed:20079333}.;

Recessive Scores

pRec: 0.214

Intolerance Scores

LoFtool: 0.236
RVIS EVS: -0.25
RVIS percentile EVS: 35.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

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