GeneBe

PUS3

protein-coding

pseudouridine synthase 3, the group of Pseudouridine synthases

Gene summary

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]

MANE transcript

NM_031307.4

Inheritance

AR

ClinVar variants

P:20U:107B:44

Top phenotype

Neurodevelopmental disorder with microcephaly and gray sclerae

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr11:125,893,485-125,903,221

External References & Databases

Ensembl (ENSG00000110060)NCBI Gene (83480)OMIM (616283)HGNC:25461GenCCUniProt (Q9BZE2)AlphaFoldClinVar (PUS3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~9.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014886

Submitter: Labcorp Genetics (formerly Invitae)

severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014886

Submitter: PanelApp Australia

severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014886

Submitter: G2P

severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014886

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with microcephaly and gray scleraeAR

Manifestation: Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27055666; 28454995; 30308082; 32056211Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PUS3 variants in ClinVar

16 Conditions Cataloged
not providedTotal: 234
Inborn genetic diseasesTotal: 117
Hydrolethalus syndromeTotal: 57
Hydrolethalus syndrome 1Total: 31
Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndromeTotal: 17
PUS3-related disorderTotal: 11
not specifiedTotal: 11
HYLS1-related disordersTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031307.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
31
clinvar
2
clinvar
 33
missense
3
clinvar
106
clinvar
9
clinvar
2
clinvar
 120
nonsense
2
clinvar
4
clinvar
 6
start loss
2
clinvar
1
clinvar
 3
frameshift
2
clinvar
6
clinvar
1
clinvar
 9
splice donor/acceptor (+/-2bp)
0
Total614107404171

Highest pathogenic variant AF is 0.000621345

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_031307.4RefSeqNP_112597.43MANE Select
ENST00000227474.8EnsemblENSP00000227474.33MANE Select
NM_001271985.2RefSeqNP_001258914.12Standard
NM_001441237.1RefSeqNP_001428166.13Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • tRNA modification in the nucleus and cytosol
  • tRNA processing
  • Metabolism of RNA

Biological Process

  • tRNA modification
  • tRNA pseudouridine synthesis
  • mRNA pseudouridine synthesis

Molecular Function

  • RNA binding
  • pseudouridine synthase activity
  • tRNA pseudouridine synthase activity

Cellular Component

  • nucleus
  • cytoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000227474
Coding exons
3
Length
9736
Individuals with no LoFs
125696
Homozygous LoFs
0
Heterozygous LoFs
52
Defined
125748
p
0.000207
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.1342612670.9770.00001433190
Missense (PolyPhen)6569.5480.9346764
Synonymous0.1348889.60.9820.00000426906
Loss of Function1.161520.70.7240.00000142208

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000310.00031rare
Latino/Admixed American0.000150.00014rare
Ashkenazi Jewish00.0absent
East Asian0.000160.00016rare
Finnish00.0absent
European (Non-Finnish)0.000160.00016rare
South Asian0.000690.00069rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Formation of pseudouridine at position 39 in the anticodon stem and loop of transfer RNAs. {ECO:0000269|PubMed:27055666}.;
Disease
DISEASE: Mental retardation, autosomal recessive 55 (MRT55) [MIM:617051]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:27055666}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.110

Intolerance Scores

LoFtool
0.902
RVIS EVS
0.24
RVIS percentile EVS
69.51

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Indispensability pred.
N
Indispensability score
0.0602

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.