ALG12

Chr 22AR

ALG12 alpha-1,6-mannosyltransferase

Also known as: CDG1G, ECM39, PP14673, hALG12

NCBI Gene: 79087ENSG00000182858UniProt: Q9BV10

This gene encodes a member of the glycosyltransferase 22 family. The encoded protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ig (CDG-Ig)characterized by abnormal N-glycosylation. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IgMIM #607143
AR
937
ClinVar variants
62
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALG12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 Pathogenic / Likely Pathogenic· 246 VUS of 937 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.
1.03LOEUF
pLI 0.000
Z-score 1.45
OE 0.66 (0.43–1.03)
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.
-0.19Z-score
OE missense 1.03 (0.94–1.14)
295 obs / 285.8 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.0.66 (0.43–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.94–1.14)
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.1.20
0≤1.21.6
LoF obs/exp: 14 / 21.2Missense obs/exp: 295 / 285.8Syn Z: -1.87

ClinVar Variant Classifications

937 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic11
VUS246
Likely Benign152
Benign20
Conflicting4
51
Pathogenic
11
Likely Pathogenic
246
VUS
152
Likely Benign
20
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
44
0
51
Likely Pathogenic
10
1
0
0
11
VUS
2
230
12
2
246
Likely Benign
0
15
34
103
152
Benign
0
1
19
0
20
Conflicting
—4
Total19247109105484

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

View in ClinVar →

Protein Context — Lollipop Plot

ALG12 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ALG12-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 Ig

MIM #607143

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature.
Tahata S et al.·Mol Genet Metab
2019Review
Restoration of N-glycosylation via leucine-activated leucyl-tRNA synthetase 1 overcomes chemoresistance in intrahepatic cholangiocarcinoma.
Liu H et al.·J Hepatol
2026
ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant.
de la Morena-Barrio ME et al.·Mol Genet Genomic Med
2020Case report
Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
Shanmugasundaram M et al.·Am J Med Genet A
2024Case report
Novel ALG12 variants and hydronephrosis in siblings with impaired N-glycosylation.
Hiraide T et al.·Brain Dev
2021Case report
A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
Ziburová J et al.·Am J Med Genet A
2021
ALG12-CDG: novel glycophenotype insights endorse the molecular defect.
Sturiale L et al.·Glycoconj J
2019
ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
Grubenmann CE et al.·Hum Mol Genet
2002Case report
An ALG12-CDG patient with a novel homozygous intronic mutation associated with low ALG12 mRNA.
Vuillaumier-Barrot S et al.·Orphanet J Rare Dis
2025Case report
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