ALG6

Chr 1AR

ALG6 alpha-1,3-glucosyltransferase

Also known as: CDG1C

NCBI Gene: 29929 ENSG00000088035 UniProt: Q9Y672 OMIM: 604566

The protein catalyzes the addition of the first glucose residue to lipid-linked oligosaccharide precursors during N-linked glycosylation in the endoplasmic reticulum. Mutations cause congenital disorder of glycosylation type Ic, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant negative effects from the mutant protein.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the first glucose residue to the growing lipid-linked oligosaccharide precursor of N-linked glycosylation. Mutations in this gene are associated with congenital disorders of glycosylation type Ic. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.641 OMIM phenotype

Clinical Summary— ALG6

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Gene-Disease Validity (ClinGen)

ALG6-congenital disorder of glycosylation 1C · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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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

160 unique Pathogenic / Likely Pathogenic· 264 VUS of 892 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ALG6

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?

0.64LOEUF

pLI 0.000

Z-score 3.03

OE 0.39 (0.24–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.53Z-score

OE missense 0.73 (0.65–0.83)

191 obs / 260.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.24–0.64)

0≤0.351.4

Missense OE?0.73 (0.65–0.83)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 11 / 28.4Missense obs/exp: 191 / 260.3Syn Z: 0.60

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveALG6-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

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

0.6939th %ile

GOF

0.5661th %ile

LOF

0.2775th %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

892 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50

Likely Pathogenic110

VUS264

Likely Benign391

Benign39

Conflicting21

Pathogenic

110

Likely Pathogenic

264

VUS

391

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	40	1	9	0	50
Likely Pathogenic	98	8	4	0	110
VUS	4	209	43	8	264
Likely Benign	0	8	181	202	391
Benign	0	1	36	2	39
Conflicting	—				21
Total	142	227	273	212	875

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap ALG6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →