ALG5

Chr 13

ALG5 dolichyl-phosphate beta-glucosyltransferase

Also known as: PKD7, bA421P11.2

NCBI Gene: 29880 ENSG00000120697 UniProt: Q9Y673

The ALG5 protein is a dolichyl-phosphate beta-glucosyltransferase that produces the glucose donor substrate essential for the final steps of N-linked protein glycosylation in the endoplasmic reticulum. Mutations cause polycystic kidney disease 7, which follows autosomal dominant inheritance. The gene shows significant constraint against loss-of-function variants (LOEUF 0.453), indicating that complete loss of ALG5 function is likely incompatible with normal development.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the glycosyltransferase 2 family. The encoded protein participates in glucosylation of the oligomannose core in N-linked glycosylation of proteins. The addition of glucose residues to the oligomannose core is necessary to ensure substrate recognition, and therefore, effectual transfer of the oligomannose core to the nascent glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPolycystic kidney disease 7

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · autosomal dominant polycystic kidney disease · AD · ClinGen 2023

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

—

Mechanism

📖

GeneReview available — ALG5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.463

Z-score 3.50

OE 0.22 (0.11–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.01Z-score

OE missense 0.79 (0.69–0.91)

143 obs / 181.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.11–0.45)

0≤0.351.4

Missense OE?0.79 (0.69–0.91)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 5 / 23.2Missense obs/exp: 143 / 181.1Syn Z: -0.28

Background carrier burden — how many people carry a rare variant somewhere in ALG5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

368 rare PASS variants

Rare truncating (LoF)

1 in 4,800

50 rare PASS variants

Rare synonymous (reference)

1 in 210

153 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ALG5. 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 330	1 in 4,100
South Asian	~43k	1 in 140	1 in 4,000
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 7,400
European (Finnish)	~27k	1 in 580	≈ 1 in 27,000
Admixed American	~22k	1 in 140	1 in 3,700
African / African American	~21k	1 in 150	≈ 1 in 21,000
East Asian	~20k	1 in 160	1 in 2,600
Ashkenazi Jewish	~13k	1 in 620	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 95	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 10 coding exons well covered in gnomAD exomes; exons 7, 9 marginal. Genomes: all 10.? see exons ↓