UGGT2

Chr 13

UDP-glucose glycoprotein glucosyltransferase 2

Also known as: HUGT2, UGCGL2, UGT2

NCBI Gene: 55757 ENSG00000102595 UniProt: Q9NYU1 OMIM: 605898

UGGT2 encodes UDP-glucose:glycoprotein glucosyltransferase, which provides quality control for protein folding in the endoplasmic reticulum by reglucosylating misfolded glycoproteins to allow their recognition by calreticulin for refolding or degradation. Mutations cause autosomal recessive intellectual disability with distinctive facial features and variable congenital anomalies. The gene shows tolerance to loss-of-function variation in the general population.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.06LOEUF

pLI 0.000

Z-score 1.10

OE 0.87 (0.71–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.00 (0.94–1.06)

761 obs / 759.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.87 (0.71–1.06)

0≤0.351.4

Missense OE?1.00 (0.94–1.06)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 69 / 79.6Missense obs/exp: 761 / 759.4Syn Z: 1.90

Background carrier burden — how many people carry a rare variant somewhere in UGGT2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 27

2,020 rare PASS variants

Rare truncating (LoF)

1 in 300

419 rare PASS variants

Rare synonymous (reference)

1 in 96

623 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UGGT2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 40	1 in 330
South Asian	~43k	1 in 28	1 in 130
Remaining (unassigned)	~30k	1 in 24	1 in 340
European (Finnish)	~27k	1 in 75	1 in 390
Admixed American	~22k	1 in 33	1 in 220
African / African American	~21k	1 in 26	1 in 290
East Asian	~20k	1 in 33	1 in 250
Ashkenazi Jewish	~13k	1 in 140	1 in 650
Middle Eastern	~2,884	1 in 31	1 in 460

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 30 of 39 coding exons well covered in gnomAD exomes; exons 4, 8, 10, 13, 16 and 4 more marginal. Genomes: all 39.? see exons ↓