PUS3

pseudouridine synthase 3, the group of Pseudouridine synthases

Basic information

Region (hg38): 11:125893484-125903221

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

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 (193 variants)
• Inborn genetic diseases (37 variants)
• Hydrolethalus syndrome (19 variants)
• Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome (14 variants)
• Hydrolethalus syndrome 1 (13 variants)
• not specified (4 variants)
• Dandy-Walker syndrome (2 variants)
• Genetic syndrome with a Dandy-Walker malformation as major feature;Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome (1 variants)
• - (1 variants)
• PUS3-related condition (1 variants)
• Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome;Genetic syndrome with a Dandy-Walker malformation as major feature (1 variants)
• Anencephaly;Heart, malformation of;Polyhydramnios;Ankle flexion contracture;Aplasia/Hypoplasia of the cerebellum (1 variants)
• Aplasia/Hypoplasia of the cerebellum;Heart, malformation of;Polyhydramnios;Anencephaly;Ankle flexion contracture (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	18	3	22
missense		1	56	4	6	67
nonsense	1	2				3
start loss	2	1				3
frameshift	1	4	1			6
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region				1		1
non coding	1	2	28	95	9	135
Total	5	10	89	117	18

Highest pathogenic variant AF is 0.000945

Variants in PUS3

This is a list of pathogenic ClinVar variants found in the PUS3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-125893822-C-T			Uncertain significance (Aug 21, 2022)
11-125893827-C-T			Likely benign (Dec 11, 2023)
11-125893851-C-G		Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome	Benign (Jan 31, 2024)
11-125893862-G-A			Likely benign (Apr 09, 2018)
11-125893870-T-C		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
11-125893892-TTTC-T			Uncertain significance (Jul 14, 2022)
11-125893903-T-C		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
11-125893911-A-G			Likely benign (Sep 27, 2022)
11-125893924-A-G		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
11-125893928-G-A		Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome	Pathogenic (Mar 14, 2024)
11-125893930-C-T		Inborn genetic diseases	Uncertain significance (May 11, 2022)
11-125893935-A-G			Likely benign (Aug 09, 2022)
11-125893936-C-T			Uncertain significance (Dec 02, 2022)
11-125893937-G-A			Uncertain significance (Jul 17, 2023)
11-125893966-C-A		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
11-125893967-C-T		PUS3-related disorder	Benign (Oct 14, 2023)
11-125893981-C-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2023)
11-125893982-G-A			Uncertain significance (Mar 20, 2022)
11-125893989-G-C			Likely benign (Aug 24, 2023)
11-125894007-C-T		Inborn genetic diseases	Likely benign (Jan 24, 2024)
11-125894011-T-C			Uncertain significance (Feb 22, 2022)
11-125894017-CCTT-C		Inborn genetic diseases	Uncertain significance (Jan 16, 2022)
11-125894018-C-T			Uncertain significance (Jul 26, 2022)
11-125894048-CAG-C		Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome	Likely pathogenic (-)
11-125894082-A-G		PUS3-related disorder	Likely benign (Nov 21, 2023)

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