PUS3

Chr 11AR

pseudouridine synthase 3

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

NCBI Gene: 83480 ENSG00000110060 UniProt: Q9BZE2 OMIM: 616283

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene catalyzes the formation of tRNA pseudouridine from tRNA uridine at position 39 in the anticodon stem and loop of transfer RNAs. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.111 OMIM phenotype

Clinical Summary— PUS3

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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

38 unique Pathogenic / Likely Pathogenic· 180 VUS of 409 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?

1.11LOEUF

pLI 0.000

Z-score 1.16

OE 0.72 (0.48–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.88–1.08)

261 obs / 267.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.48–1.11)

0≤0.351.4

Missense OE?0.98 (0.88–1.08)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

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

This gene — mechanism propensity

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

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

409 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic30

VUS180

Likely Benign162

Benign16

Conflicting7

Pathogenic

Likely Pathogenic

180

VUS

162

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	3	0	0	8
Likely Pathogenic	28	2	0	0	30
VUS	7	169	2	2	180
Likely Benign	0	8	5	149	162
Benign	0	8	5	3	16
Conflicting	—				7
Total	40	190	12	154	403

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

View in ClinVar →

64 pathogenic / likely-pathogenic (of 69) ClinVar copy-number / structural variants overlap PUS3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →