PUS3

pseudouridine synthase 3, the group of Pseudouridine synthases

Basic information

Region (hg38): 11:125893485-125903221

Links

ENSG00000110060 ∙ NCBI:83480 ∙ OMIM:616283 ∙ HGNC:25461 ∙ Uniprot:Q9BZE2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome (Moderate), mode of inheritance: AR
• severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome (Strong), mode of inheritance: AR
• severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly and gray sclerae	AR	General	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	Neurologic; Ophthalmologic	27055666; 28454995; 30308082; 32056211

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PUS3 gene.

• not_provided (224 variants)
• Inborn_genetic_diseases (103 variants)
• Hydrolethalus_syndrome (46 variants)
• Hydrolethalus_syndrome_1 (23 variants)
• Severe_growth_deficiency-strabismus-extensive_dermal_melanocytosis-intellectual_disability_syndrome (15 variants)
• PUS3-related_disorder (7 variants)
• not_specified (3 variants)
• Anencephaly (2 variants)
• Aplasia/Hypoplasia_of_the_cerebellum (2 variants)
• Genetic_syndrome_with_a_Dandy-Walker_malformation_as_major_feature (2 variants)
• Polyhydramnios (2 variants)
• Dandy-Walker_syndrome (2 variants)
• Ankle_flexion_contracture (2 variants)
• Heart,_malformation_of (2 variants)
• HYLS1-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PUS3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000031307.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				27	2	29
missense	1	1	94	9	2	107
nonsense	3	2				5
start loss	2	1				3
frameshift	2	5				7
splice donor/acceptor (+/-2bp)			1			1
Total	8	9	95	36	4

Highest pathogenic variant AF is 0.000621345

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PUS3	protein_coding	protein_coding	ENST00000227474	3	9736

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.40e-8	0.598	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.134	261	267	0.977	0.0000143	3190
Missense in Polyphen		65	69.548	0.9346		764
Synonymous	0.134	88	89.6	0.982	0.00000426	906
Loss of Function	1.16	15	20.7	0.724	0.00000142	208

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000459	0.000459
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000163	0.000163
South Asian	0.000686	0.000686
Other	0.00	0.00

dbNSFP

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.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.902
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.51

Haploinsufficiency Scores

• pHI: 0.226
• hipred: N
• hipred_score: 0.197
• ghis: 0.484

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0602

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pus3

Gene ontology

• Biological process: tRNA modification;tRNA pseudouridine synthesis;mRNA pseudouridine synthesis
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: RNA binding;pseudouridine synthase activity;tRNA pseudouridine synthase activity