ALG12

Chr 22AR

ALG12 alpha-1,6-mannosyltransferase

Also known as: CDG1G, ECM39, PP14673, hALG12

NCBI Gene: 79087 ENSG00000182858 UniProt: Q9BV10 OMIM: 607144

This protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor required for N-linked protein glycosylation. Mutations cause congenital disorder of glycosylation type Ig (CDG-Ig) through autosomal recessive inheritance, resulting in abnormal N-glycosylation due to loss of enzyme function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the glycosyltransferase 22 family. The encoded protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ig (CDG-Ig)characterized by abnormal N-glycosylation. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.031 OMIM phenotype

Clinical Summary— ALG12

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Gene-Disease Validity (ClinGen)

ALG12-congenital disorder of glycosylation · ARDefinitive

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

45 unique Pathogenic / Likely Pathogenic· 398 VUS of 794 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?

1.03LOEUF

pLI 0.000

Z-score 1.45

OE 0.66 (0.43–1.03)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.19Z-score

OE missense 1.03 (0.94–1.14)

295 obs / 285.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.43–1.03)

0≤0.351.4

Missense OE?1.03 (0.94–1.14)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 14 / 21.2Missense obs/exp: 295 / 285.8Syn Z: -1.87

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveALG12-related congenital disorder of glycosylationLOFAR

This gene — mechanism propensity

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

0.6745th %ile

GOF

0.6052th %ile

LOF

0.2969th %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

794 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23

Likely Pathogenic22

VUS398

Likely Benign256

Benign45

Conflicting34

Pathogenic

Likely Pathogenic

398

VUS

256

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	21	1	1	0	23
Likely Pathogenic	16	6	0	0	22
VUS	2	363	29	4	398
Likely Benign	0	20	66	170	256
Benign	0	4	32	9	45
Conflicting	—				34
Total	39	394	128	183	778

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

View in ClinVar →

140 pathogenic / likely-pathogenic (of 149) ClinVar copy-number / structural variants overlap ALG12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →