ALG14

Chr 1AR

ALG14 UDP-N-acetylglucosaminyltransferase subunit

Also known as: CMS15, IDDEBF, MEPCA

The protein forms a subunit of UDP-GlcNAc transferase with ALG13, catalyzing the first two committed steps in endoplasmic reticulum N-linked glycosylation. Autosomal recessive mutations cause congenital myasthenic syndrome without tubular aggregates, intellectual developmental disorder with epilepsy and behavioral abnormalities, or myopathy with epilepsy and progressive cerebral atrophy. The pathogenic mechanism appears to involve dominant-negative effects disrupting the glycosylation pathway.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 1.203 OMIM phenotypes
Clinical SummaryALG14
🧬
Gene-Disease Validity (ClinGen)
congenital disorder of glycosylation · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — ALG14
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.20LOEUF
pLI 0.001
Z-score 1.15
OE 0.61 (0.331.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.27Z-score
OE missense 0.93 (0.801.09)
118 obs / 126.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.331.20)
00.351.4
Missense OE0.93 (0.801.09)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 6 / 9.9Missense obs/exp: 118 / 126.4Syn Z: 0.55
DN
0.7035th %ile
GOF
0.6345th %ile
LOF
0.2970th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ALG14 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →