ALG8

Chr 11ARAD

ALG8 alpha-1,3-glucosyltransferase

Also known as: CDG1H, PCLD3

NCBI Gene: 79053 ENSG00000159063 UniProt: Q9BVK2 OMIM: 608103

The encoded protein catalyzes the addition of the second glucose residue to lipid-linked oligosaccharide precursors during N-linked glycosylation of proteins in the endoplasmic reticulum. Mutations cause congenital disorder of glycosylation type Ih and polycystic liver disease 3 with or without kidney cysts, following both autosomal recessive and autosomal dominant inheritance patterns. The pathogenic mechanism involves dominant-negative effects.

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 second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismAR/ADLOEUF 0.832 OMIM phenotypes

Clinical Summary— ALG8

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Gene-Disease Validity (ClinGen)

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

66 unique Pathogenic / Likely Pathogenic· 214 VUS of 485 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.000

Z-score 2.31

OE 0.56 (0.39–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.60Z-score

OE missense 0.90 (0.81–1.00)

240 obs / 267.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.39–0.83)

0≤0.351.4

Missense OE?0.90 (0.81–1.00)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 18 / 32.1Missense obs/exp: 240 / 267.8Syn Z: -0.97

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveALG8-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

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

0.75top 25%

GOF

0.5758th %ile

LOF

0.2385th %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

485 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18

Likely Pathogenic48

VUS214

Likely Benign111

Benign65

Conflicting23

Pathogenic

Likely Pathogenic

214

VUS

111

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	3	1	0	18
Likely Pathogenic	44	3	1	0	48
VUS	7	178	23	6	214
Likely Benign	0	10	65	36	111
Benign	0	0	63	2	65
Conflicting	—				23
Total	65	194	153	44	479

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap ALG8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →