ALG9

Chr 11AR

ALG9 alpha-1,2-mannosyltransferase

Also known as: CDG1L, DIBD1, GIKANIS, LOH11CR1J

NCBI Gene: 79796ENSG00000086848UniProt: Q9H6U8

This gene encodes an alpha-1,2-mannosyltransferase enzyme that functions in lipid-linked oligosaccharide assembly. Mutations in this gene result in congenital disorder of glycosylation type Il. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IlMIM #608776
AR
Gillessen-Kaesbach-Nishimura syndromeMIM #263210
AR
409
ClinVar variants
54
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALG9
🧬
Gene-Disease Validity (ClinGen)
ALG9-associated 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
54 Pathogenic / Likely Pathogenic· 182 VUS of 409 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.
0.65LOEUF
pLI 0.001
Z-score 2.91
OE 0.38 (0.24–0.65)
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.
1.01Z-score
OE missense 0.81 (0.72–0.92)
190 obs / 233.4 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.0.38 (0.24–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.72–0.92)
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.0.95
0≤1.21.6
LoF obs/exp: 10 / 26.0Missense obs/exp: 190 / 233.4Syn Z: 0.37

ClinVar Variant Classifications

409 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic22
VUS182
Likely Benign124
Benign33
Conflicting16
32
Pathogenic
22
Likely Pathogenic
182
VUS
124
Likely Benign
33
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
2
25
0
32
Likely Pathogenic
12
1
9
0
22
VUS
2
104
71
5
182
Likely Benign
0
6
64
54
124
Benign
0
4
29
0
33
Conflicting
—16
Total1911719859409

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

View in ClinVar →

Protein Context — Lollipop Plot

ALG9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ALG9-related congenital disorder of glycosylation

strong
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 Il

MIM #608776

Molecular basis of disorder known

Autosomal recessive

Gillessen-Kaesbach-Nishimura syndrome

MIM #263210

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ALG9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype.
Senum SR et al.·Am J Hum Genet
2022
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Exome Sequencing of a Clinical Population for Autosomal Dominant Polycystic Kidney Disease.
Chang AR et al.·JAMA
2022
Missense variant c.1460 T > C (p.L487P) enhances protein degradation of ER mannosyltransferase ALG9 in two new ALG9-CDG patients presenting with West syndrome and review of the literature.
Himmelreich N et al.·Mol Genet Metab
2022Review
Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease.
Mahboobipour AA et al.·Orphanet J Rare Dis
2024Review
Heterozygosity of ALG9 in Association with Autosomal Dominant Polycystic Liver Disease.
Boerrigter MM et al.·Genes (Basel)
2023
Typical and atypical ADPKD: predicted pathogenic genetic variants and population frequencies.
Varughese S et al.·Nephrol Dial Transplant
2026
ALG9 Mutation Carriers Develop Kidney and Liver Cysts.
Besse W et al.·J Am Soc Nephrol
2019
A novel phenotype in N-glycosylation disorders: Gillessen-Kaesbach-Nishimura skeletal dysplasia due to pathogenic variants in ALG9.
Tham E et al.·Eur J Hum Genet
2016
Phenotypic outcomes of PKD1 compared with non-PKD1 genetically confirmed autosomal dominant polycystic kidney disease.
Elhassan EAE et al.·J Nephrol
2025
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