ALG9

Chr 11AR

ALG9 alpha-1,2-mannosyltransferase

Also known as: CDG1L, DIBD1, GIKANIS, LOH11CR1J

NCBI Gene: 79796 ENSG00000086848 UniProt: Q9H6U8 OMIM: 606941

The protein is an alpha-1,2-mannosyltransferase enzyme that functions in lipid-linked oligosaccharide assembly in the endoplasmic reticulum membrane. Mutations cause congenital disorder of glycosylation type Il and Gillessen-Kaesbach-Nishimura syndrome through autosomal recessive inheritance. The pathogenic mechanism involves disruption of the glycosylation pathway due to defective oligosaccharide assembly.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IlMIM #608776

Gillessen-Kaesbach-Nishimura syndromeMIM #263210

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ALG9-associated autosomal dominant polycystic kidney disease · AD · 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

0.65

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ALG9

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.001

Z-score 2.91

OE 0.38 (0.24–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.01Z-score

OE missense 0.81 (0.72–0.92)

190 obs / 233.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.24–0.65)

0≤0.351.4

Missense OE?0.81 (0.72–0.92)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 10 / 26.0Missense obs/exp: 190 / 233.4Syn Z: 0.37

Background carrier burden — how many people carry a rare variant somewhere in ALG9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

693 rare PASS variants

Rare truncating (LoF)

1 in 2,000

117 rare PASS variants

Rare synonymous (reference)

1 in 120

304 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ALG9. 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 1,700
South Asian	~43k	1 in 95	1 in 2,200
Remaining (unassigned)	~30k	1 in 76	1 in 920
European (Finnish)	~27k	1 in 150	1 in 4,100
Admixed American	~22k	1 in 72	1 in 1,600
African / African American	~21k	1 in 100	≈ 1 in 4,600
East Asian	~20k	1 in 130	1 in 1,300
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 140	≈ 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): 15 of 15 coding exons well covered in gnomAD exomes. Genomes: 14 of 15 (exon 2 below).? see exons ↓