AGMO

protein-coding

alkylglycerol monooxygenase, the group of Fatty acid hydroxylase domain containing

Gene summary

The protein encoded by this gene is a tetrahydrobiopterin- and iron-dependent enzyme that cleaves the ether bond of alkylglycerols. Sequence comparisons distinguish this protein as forming a third, distinct class of tetrahydrobiopterin-dependent enzymes. Variations in this gene have been associated with decreased glucose-stimulated insulin response, type 2 diabetes, and susceptibility to intracranial aneurysms. [provided by RefSeq, Aug 2012]

Previous symbols:

TMEM195

MANE transcript

NM_001004320.2

Inheritance

AD, AR

ClinVar variants

P:4U:128B:19

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 1.29

Max pathogenic AF

—

Genomic locus

chr7:15,200,317-15,562,015

External References & Databases

Ensembl (ENSG00000187546)

Transcript & Mutation Effects

hg38 • Region Span ~361.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGMO variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 109

not providedTotal: 39

AGMO-related disorderTotal: 16

AGMO-related Neurodevelopmental disorderTotal: 3

See casesTotal: 2

Hypercholesterolemia, familial, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001004320.2. 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			2 clinvar	2 clinvar	2 clinvar	6
missense			113 clinvar	8 clinvar	6 clinvar	127
nonsense			3 clinvar			3
start loss						0
frameshift	2 clinvar		6 clinvar		1 clinvar	9
splice donor/acceptor (+/-2bp)		2 clinvar	4 clinvar			6
Total	2	2	128	10	9	151

Highest pathogenic variant AF is 0.00012154652

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001004320.2	RefSeq	NP_001004320.1	13	MANE Select
ENST00000342526.8	Ensembl	ENSP00000341662.3	13	MANE Select
ENST00000407277.6	Ensembl	ENSP00000385742.2	3	Standard
ENST00000418075.1	Ensembl	ENSP00000394412.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
Triglyceride biosynthesis
Triglyceride metabolism

Biological Process

membrane lipid metabolic process
triglyceride biosynthetic process
ether lipid metabolic process
oxidation-reduction process

Molecular Function

iron ion binding
glyceryl-ether monooxygenase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342526
Coding exons: 13
Length: 361698
Individuals with no LoFs: 124212
Homozygous LoFs: 9
Heterozygous LoFs: 1526
Defined: 125747
p: 0.00612

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.56	339	230	1.48	0.0000111	2889
Missense (PolyPhen)		86	67.856	1.2674		835
Synonymous	-3.33	116	78.4	1.48	0.00000376	836
Loss of Function	-1.37	34	26.4	1.29	0.00000127	312

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0043	0.0043	notable
Latino/Admixed American	0.0033	0.0032	notable
Ashkenazi Jewish	0.011	0.011	notable
East Asian	0.0012	0.0012	notable
Finnish	0.017	0.017	notable
European (Non-Finnish)	0.0068	0.0067	notable
South Asian	0.0015	0.0015	notable
Other	0.0078	0.0072	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Glyceryl-ether monooxygenase that cleaves the O-alkyl bond of ether lipids. Ether lipids are essential components of brain membranes. {ECO:0000269|PubMed:20643956}.;

Recessive Scores

pRec: 0.123

Intolerance Scores

RVIS EVS: 0.4
RVIS percentile EVS: 76.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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