ALG1

Chr 16

ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase

Also known as: CDG1K, HMAT1, HMT-1, HMT1, MT-1, Mat-1, hMat-1

NCBI Gene: 56052ENSG00000033011UniProt: Q9BT22

The enzyme encoded by this gene catalyzes the first mannosylation step in the biosynthesis of lipid-linked oligosaccharides. This gene is mutated in congenital disorder of glycosylation type Ik. [provided by RefSeq, Dec 2008]

Primary Disease Associations & Inheritance

UniProtCongenital disorder of glycosylation 1K
583
ClinVar variants
109
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALG1
🧬
Gene-Disease Validity (ClinGen)
ALG1-congenital disorder of glycosylation · ARDefinitive

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
109 Pathogenic / Likely Pathogenic· 190 VUS of 583 total submissions
Some data sources returned errors (2)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

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.
1.50LOEUF
pLI 0.000
Z-score -0.41
OE 1.09 (0.80–1.50)
Tolerant

Highly tolerant — LoF variants common in population

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.
-2.05Z-score
OE missense 1.35 (1.24–1.48)
357 obs / 263.5 exp
Tolerant

Tolerant to missense variation

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.1.09 (0.80–1.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.35 (1.24–1.48)
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.1.45
0≤1.21.6
LoF obs/exp: 27 / 24.8Missense obs/exp: 357 / 263.5Syn Z: -3.74

ClinVar Variant Classifications

583 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic47
VUS190
Likely Benign257
Benign5
Conflicting22
62
Pathogenic
47
Likely Pathogenic
190
VUS
257
Likely Benign
5
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
6
37
0
62
Likely Pathogenic
24
16
6
1
47
VUS
1
161
26
2
190
Likely Benign
0
6
122
129
257
Benign
0
0
5
0
5
Conflicting
—22
Total44189196132583

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

View in ClinVar →

Protein Context — Lollipop Plot

ALG1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — ALG1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A novel variant in ALG1 gene associated with congenital disorder of glycosylation: A case report and short literature review.
Xue Y et al.·Mol Genet Genomic Med
2023Review
ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients.
Ng BG et al.·Hum Mutat
2016Cohort
Dysregulated proteome and N-glycoproteome in ALG1-deficient fibroblasts.
Budhraja R et al.·Proteomics
2024
Clinical and genetic characterization of congenital disorders of glycosylation in 20 Chinese patients.
Zhao P et al.·Orphanet J Rare Dis
2025Cohort
Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up.
Bogdańska A et al.·Orphanet J Rare Dis
2021Natural history
Case Report of Friedreich's Ataxia and ALG1 -Related Biochemical Abnormalities in a Patient With Progressive Spastic Paraplegia.
Quinlan A et al.·Am J Med Genet A
2025Case report
Defining the phenotype in congenital disorder of glycosylation due to ALG1 mutations.
Morava E et al.·Pediatrics
2012Case report
Analysis of clinical phenotypic and genotypic spectra in 36 children patients with Epilepsy of Infancy with Migrating Focal Seizures.
Yang H et al.·Sci Rep
2022Cohort
Deficient glycan extension and endoplasmic reticulum stresses in ALG3-CDG.
Daniel EJP et al.·J Inherit Metab Dis
2024
Congenital Disorders of Glycosylation in Portugal-Two Decades of Experience.
Quelhas D et al.·J Pediatr
2021
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