ALG9

Chr 11

ALG9 alpha-1,2-mannosyltransferase

Also known as: CDG1L, DIBD1, GIKANIS, LOH11CR1J

NCBI Gene: 79796 ENSG00000086848 UniProt: Q9H6U8

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 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 ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.65

Clinical Summary— ALG9

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Gene-Disease Validity (ClinGen)

ALG9-associated autosomal dominant polycystic kidney disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

39 unique Pathogenic / Likely Pathogenic· 177 VUS of 405 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ALG9

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongALG9-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6260th %ile

GOF

0.5269th %ile

LOF

0.3355th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

405 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic24

VUS177

Likely Benign125

Benign33

Conflicting16

Pathogenic

Likely Pathogenic

177

VUS

125

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	2	2	0	15
Likely Pathogenic	21	2	1	0	24
VUS	4	105	63	5	177
Likely Benign	0	7	64	54	125
Benign	0	4	29	0	33
Conflicting	—				16
Total	36	120	159	59	390

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap ALG9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →