UGGT1

protein-coding

UDP-glucose glycoprotein glucosyltransferase 1, the group of UDP-glucose glycoprotein glucosyltransferases

Gene summary

UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that selectively reglucosylates unfolded glycoproteins, thus providing quality control for protein transport out of the ER.[supplied by OMIM, Oct 2009]

Previous symbols:

UGCGL1

MANE transcript

NM_020120.4

Inheritance

ClinVar variants

P:9U:204B:22

Top phenotype

Congenital disorder of glycosylation, type IIcc

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr2:128,091,200-128,195,677

External References & Databases

Ensembl (ENSG00000136731)

Transcript & Mutation Effects

hg38 • Region Span ~104.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

disorder of protein N-glycosylationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0017740

Submitter: Ambry Genetics

congenital disorder of glycosylationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0015286

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UGGT1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 187

not providedTotal: 28

Congenital disorder of glycosylation, type IIccTotal: 9

Hypercholesterolemia, familial, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020120.4. 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			3 clinvar	2 clinvar	7 clinvar	12
missense	4 clinvar		192 clinvar	8 clinvar	5 clinvar	209
nonsense	1 clinvar		2 clinvar			3
start loss						0
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	8	1	204	10	12	235

Highest pathogenic variant AF is 0.0000065706477

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020120.4	RefSeq	NP_064505.1	41	MANE Select
ENST00000259253.11	Ensembl	ENSP00000259253.6	41	MANE Select
ENST00000376723.7	Ensembl	ENSP00000365913.3	1	Standard
ENST00000418197.1	Ensembl	ENSP00000389441.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
er associated degradation (erad) pathway
ER Quality Control Compartment (ERQC)
Calnexin/calreticulin cycle
Post-translational protein modification

Biological Process

protein N-linked glycosylation via asparagine
'de novo' posttranslational protein folding
ER-associated misfolded protein catabolic process
UDP-glucosylation
endoplasmic reticulum mannose trimming

Molecular Function

UDP-glucose:glycoprotein glucosyltransferase activity
protein binding
unfolded protein binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum lumen
endoplasmic reticulum-Golgi intermediate compartment
protein-containing complex
endoplasmic reticulum quality control compartment

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259253
Coding exons: 41
Length: 104478
Individuals with no LoFs: 125675
Homozygous LoFs: 0
Heterozygous LoFs: 72
Defined: 125747
p: 0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	737	824	0.894	0.0000426	10273
Missense (PolyPhen)		181	264.38	0.68463		3211
Synonymous	1.27	274	302	0.907	0.0000167	2858
Loss of Function	5.56	33	89.9	0.367	0.00000444	1101

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00027	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00040	0.00040	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic reticulum. Reglucosylated proteins are recognized by calreticulin for recycling to the endoplasmic reticulum and refolding or degradation. {ECO:0000269|PubMed:10694380}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.814
RVIS EVS: -1.16
RVIS percentile EVS: 6.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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