TUSC3

Chr 8AR

tumor suppressor candidate 3

Also known as: D8S1992, M33, MRT22, MRT7, MagT2, N33, OST3A, SLC58A2

The TUSC3 protein functions as an accessory component of the N-oligosaccharyl transferase complex in the endoplasmic reticulum, catalyzing N-linked protein glycosylation and facilitating glycosylation of acceptor sites near cysteine residues. Homozygous mutations cause autosomal recessive intellectual developmental disorder, with this gene being extremely intolerant to loss-of-function variants (pLI ~0.000003). The disorder follows an autosomal recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 7MIM #611093
AR
0
Active trials
6
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.93
LOEUF
LOF
Mechanism· G2P
Clinical SummaryTUSC3
🧬
Gene-Disease Validity (ClinGen)
intellectual disability · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.000
Z-score 1.82
OE 0.57 (0.360.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.05Z-score
OE missense 1.01 (0.901.14)
197 obs / 195.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.360.93)
00.351.4
Missense OE1.01 (0.901.14)
00.61.4
Synonymous OE1.48
01.21.6
LoF obs/exp: 12 / 21.0Missense obs/exp: 197 / 195.1Syn Z: -3.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTUSC3-related intellectual developmental disorderLOFAR

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

DN
0.75top 25%
GOF
0.6051th %ile
LOF
0.3356th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TUSC3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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