MGAM

protein-coding

maltase-glucoamylase, the group of Glycoside hydrolase family 31

Gene summary

This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001365693.1

Inheritance

—

ClinVar variants

U:280B:49

Top phenotype

MGAM-related disorder

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr7:141,907,813-142,106,747

External References & Databases

Ensembl (ENSG00000257335)

Transcript & Mutation Effects

hg38 • Region Span ~198.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MGAM variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 286

MGAM-related disorderTotal: 26

not providedTotal: 22

Gestational diabetes mellitus uncontrolledTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365693.1. 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	16 clinvar	4 clinvar	22
missense			274 clinvar	26 clinvar	2 clinvar	302
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar	1 clinvar		3
Total	0	0	280	43	6	329

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365693.1	RefSeq	NP_001352622.1	70	MANE Select
ENST00000475668.6	Ensembl	ENSP00000417515.2	70	MANE Select
NM_004668.3	RefSeq	NP_004659.2	47	Standard
ENST00000465654.5	Ensembl	ENSP00000419372.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Starch and sucrose metabolism - Homo sapiens (human)
Carbohydrate digestion and absorption - Homo sapiens (human)
Galactose metabolism - Homo sapiens (human)
Glycogen synthetase deficiency
Glycogenosis, Type III. Cori disease, Debrancher glycogenosis

Biological Process

maltose metabolic process
starch catabolic process
neutrophil degranulation
polysaccharide digestion

Molecular Function

catalytic activity
glucan 1,4-alpha-glucosidase activity
alpha-1,4-glucosidase activity
amylase activity
carbohydrate binding

Cellular Component

plasma membrane
integral component of membrane
apical plasma membrane
extracellular exosome
tertiary granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000549489
Coding exons: 47
Length: 198935
Individuals with no LoFs: 124145
Homozygous LoFs: 3
Heterozygous LoFs: 732
Defined: 124880
p: 0.00295

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.761	1095	1.03e+3	1.07	0.0000558	12185
Missense (PolyPhen)		327	323.05	1.0122		3637
Synonymous	-1.06	403	377	1.07	0.0000206	3506
Loss of Function	2.93	72	104	0.691	0.00000518	1203

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0031	0.0028	notable
Latino/Admixed American	0.0064	0.0063	notable
Ashkenazi Jewish	0.0027	0.0027	notable
East Asian	0.0079	0.0078	notable
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.0021	0.0021	notable
South Asian	0.0019	0.0018	notable
Other	0.0014	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May serve as an alternate pathway for starch digestion when luminal alpha-amylase activity is reduced because of immaturity or malnutrition. May play a unique role in the digestion of malted dietary oligosaccharides used in food manufacturing.;

Recessive Scores

pRec: 0.575

Intolerance Scores

LoFtool: 0.104
RVIS EVS: 2.36
RVIS percentile EVS: 98.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.134

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High