ALG3

Chr 3

ALG3 alpha-1,3- mannosyltransferase

Also known as: CDG1D, CDGS4, CDGS6, D16Ertd36e, NOT56L, Not56, not

NCBI Gene: 10195 ENSG00000214160 UniProt: Q92685

This gene encodes a protein that catalyzes the addition of the first mannose residue in an alpha 1,3 linkage to Man5GlcNAc2-PP-Dol during N-linked glycosylation in the endoplasmic reticulum. Mutations cause congenital disorder of glycosylation type Id (CDG-Id), an autosomal recessive condition characterized by abnormal N-glycosylation. The pathogenic mechanism involves defective protein glycosylation due to impaired mannose addition during the early steps of N-linked oligosaccharide assembly.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the ALG3 family. The encoded protein catalyses the addition of the first dol-P-Man derived mannose in an alpha 1,3 linkage to Man5GlcNAc2-PP-Dol. Defects in this gene have been associated with congenital disorder of glycosylation type Id (CDG-Id) characterized by abnormal N-glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.19

Clinical Summary— ALG3

🧬

Gene-Disease Validity (ClinGen)

ALG3-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

38 unique Pathogenic / Likely Pathogenic· 116 VUS of 266 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.19LOEUF

pLI 0.000

Z-score 0.89

OE 0.79 (0.54–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.32Z-score

OE missense 1.06 (0.95–1.17)

264 obs / 249.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.79 (0.54–1.19)

0≤0.351.4

Missense OE?1.06 (0.95–1.17)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 17 / 21.5Missense obs/exp: 264 / 249.9Syn Z: -0.79

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveALG3-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

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

0.6356th %ile

GOF

0.5857th %ile

LOF

0.3550th %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

266 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic21

VUS116

Likely Benign76

Benign6

Conflicting16

Pathogenic

Likely Pathogenic

116

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	5	0	0	17
Likely Pathogenic	7	12	1	1	21
VUS	1	103	8	4	116
Likely Benign	0	2	27	47	76
Benign	0	0	4	2	6
Conflicting	—				16
Total	20	122	40	54	252

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

View in ClinVar →

42 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap ALG3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →