ALG11

Chr 13

ALG11 alpha-1,2-mannosyltransferase

Also known as: CDG1P, GT8

NCBI Gene: 440138 ENSG00000253710 UniProt: Q2TAA5

The protein functions as a GDP-mannose:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase that catalyzes the transfer of the fourth and fifth mannose residues to dolichol-linked oligosaccharides on the cytosolic side of the endoplasmic reticulum during N-linked glycosylation. Mutations cause congenital disorder of glycosylation type Ip (CDG-Ip) through autosomal recessive inheritance. The pathogenic mechanism involves disruption of the early steps of N-linked protein glycosylation due to defective mannosyltransferase activity.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCongenital disorder of glycosylation 1P

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · ALG11-congenital disorder of glycosylation · AR · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.33

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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?

1.33LOEUF

pLI 0.000

Z-score 0.56

OE 0.85 (0.56–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.05Z-score

OE missense 1.01 (0.91–1.12)

258 obs / 255.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.85 (0.56–1.33)

0≤0.351.4

Missense OE?1.01 (0.91–1.12)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 14 / 16.5Missense obs/exp: 258 / 255.9Syn Z: 0.79

Background carrier burden — how many people carry a rare variant somewhere in ALG11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

607 rare PASS variants

Rare truncating (LoF)

1 in 1,700

109 rare PASS variants

Rare synonymous (reference)

1 in 170

206 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ALG11. 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 140	1 in 1,800
South Asian	~43k	1 in 110	1 in 790
Remaining (unassigned)	~30k	1 in 97	1 in 2,000
European (Finnish)	~27k	1 in 200	1 in 3,800
Admixed American	~22k	1 in 84	1 in 1,700
African / African American	~21k	1 in 120	1 in 1,700
East Asian	~20k	1 in 61	1 in 2,800
Ashkenazi Jewish	~13k	1 in 480	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 97	≈ 1 in 2,900

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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓