PUS3

Chr 11AR

pseudouridine synthase 3

Also known as: 2610020J05Rik, DEG1, FKSG32, MRT55, NEDMIGS

This gene encodes pseudouridine synthase 3, which catalyzes the formation of pseudouridine at position 39 in the anticodon stem and loop of transfer RNAs. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with microcephaly and gray sclerae. The gene shows high constraint against loss-of-function variants (LOEUF 1.115), indicating intolerance to haploinsufficiency in the general population.

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

Neurodevelopmental disorder with microcephaly and gray scleraeMIM #617051
AR
0
Active trials
5
Pubs (1 yr)
111
P/LP submissions
6%
P/LP missense
1.11
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPUS3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
89 unique Pathogenic / Likely Pathogenic· 185 VUS of 465 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.11LOEUF
pLI 0.000
Z-score 1.16
OE 0.72 (0.481.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.13Z-score
OE missense 0.98 (0.881.08)
261 obs / 267.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.481.11)
00.351.4
Missense OE0.98 (0.881.08)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 15 / 20.7Missense obs/exp: 261 / 267.2Syn Z: 0.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePUS3-related neurodevelopmental disorder with microcephaly and gray scleraeLOFAR

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

DN
0.6259th %ile
GOF
0.5464th %ile
LOF
0.3842th %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

465 submitted variants in ClinVar

Classification Summary

Pathogenic68
Likely Pathogenic21
VUS185
Likely Benign162
Benign16
Conflicting6
68
Pathogenic
21
Likely Pathogenic
185
VUS
162
Likely Benign
16
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
3
63
0
68
Likely Pathogenic
8
2
11
0
21
VUS
4
158
21
2
185
Likely Benign
0
8
5
149
162
Benign
0
8
5
3
16
Conflicting
6
Total14179105154458

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

View in ClinVar →

Protein Context — Lollipop Plot

PUS3 · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC