ALG8

Chr 11ARAD

ALG8 alpha-1,3-glucosyltransferase

Also known as: CDG1H, PCLD3

NCBI Gene: 79053ENSG00000159063UniProt: Q9BVK2

This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IhMIM #608104
AR
Polycystic liver disease 3 with or without kidney cystsMIM #617874
AD
487
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALG8
🧬
Gene-Disease Validity (ClinGen)
autosomal dominant polycystic kidney disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 217 VUS of 487 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 2.31
OE 0.56 (0.39–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.60Z-score
OE missense 0.90 (0.81–1.00)
240 obs / 267.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.39–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.81–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 18 / 32.1Missense obs/exp: 240 / 267.8Syn Z: -0.97

ClinVar Variant Classifications

487 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic46
VUS217
Likely Benign111
Benign65
Conflicting23
25
Pathogenic
46
Likely Pathogenic
217
VUS
111
Likely Benign
65
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
4
13
0
25
Likely Pathogenic
31
4
11
0
46
VUS
3
179
29
6
217
Likely Benign
0
10
65
36
111
Benign
0
0
63
2
65
Conflicting
—23
Total4219718144487

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ALG8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ALG8-related congenital disorder of glycosylation

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type Ih

MIM #608104

Molecular basis of disorder known

Autosomal recessive

Polycystic liver disease 3 with or without kidney cysts

MIM #617874

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — ALG8
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes.
Yang H et al.·Adv Kidney Dis Health
2023Review
Isolated polycystic liver disease genes define effectors of polycystin-1 function.
Besse W et al.·J Clin Invest
2017
Exome Sequencing of a Clinical Population for Autosomal Dominant Polycystic Kidney Disease.
Chang AR et al.·JAMA
2022
ALG8-CDG: Molecular and phenotypic expansion suggests clinical management guidelines.
Albokhari D et al.·J Inherit Metab Dis
2022
Expression of ALG8 in hepatocellular carcinoma and its diagnostic and prognostic significance.
Haishen Y et al.·Scand J Gastroenterol
2025
ALG8-CDG: advances in molecular and prenatal phenotyping facilitate prenatal diagnosis and genetic counseling.
Huang Y et al.·QJM
2025Case report
Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease.
Mahboobipour AA et al.·Orphanet J Rare Dis
2024Review
Individuals heterozygous for ALG8 protein-truncating variants are at increased risk of a mild cystic kidney disease.
Apple B et al.·Kidney Int
2023
A new case of ALG8 deficiency (CDG Ih).
Vesela K et al.·J Inherit Metab Dis
2009Review
ALG8-Driven Metabolic Reprogramming in Polycystic Kidney Disease: A Systematic Synthesis of Evidence Linking Glycosylation Defects to Metabolic Signaling.
Wang X et al.·IUBMB Life
2026Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools