PUS1

pseudouridine synthase 1, the group of Pseudouridine synthases

Basic information

Region (hg38): 12:131929200-131945896

Links

ENSG00000177192

∙ NCBI:80324 ∙ OMIM:608109 ∙ HGNC:15508 ∙ Uniprot:Q9Y606 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

myopathy, lactic acidosis, and sideroblastic anemia 1 (Definitive), mode of inheritance: AR
myopathy, lactic acidosis, and sideroblastic anemia 1 (Moderate), mode of inheritance: AR
myopathy, lactic acidosis, and sideroblastic anemia (Supportive), mode of inheritance: AR
myopathy, lactic acidosis, and sideroblastic anemia 1 (Strong), mode of inheritance: AR
mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, lactic acidosis, and sideroblastic anemia 1	AR	Hematologic	Severe, non-B6 responsive anemia has reportedly required transfusions	Endocrine; Hematologic; Musculoskeletal; Neurologic	7726239; 14981724; 15108122; 15103716; 17056637; 19731322; 25227147

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PUS1 gene.

not_provided (527 variants)
Myopathy,_lactic_acidosis,_and_sideroblastic_anemia_1 (84 variants)
Inborn_genetic_diseases (61 variants)
Myopathy,_lactic_acidosis,_and_sideroblastic_anemia (52 variants)
not_specified (31 variants)
PUS1-related_disorder (21 variants)
Sideroblastic_anemia (8 variants)
Inborn_mitochondrial_myopathy (8 variants)
Mitochondrial_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PUS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025215.6. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				284 clinvar	1 clinvar	285
missense		5 clinvar	149 clinvar	15 clinvar		169
nonsense	11 clinvar	7 clinvar				18
start loss		3				3
frameshift	18 clinvar	16 clinvar				34
splice donor/acceptor (+/-2bp)		10 clinvar				10
Total	29	41	149	299	1

Highest pathogenic variant AF is 0.000055407727

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PUS1	protein_coding	protein_coding	ENST00000376649	6	14662

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00167	0.974	125729	0	12	125741	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.291	250	263	0.949	0.0000171	2758
Missense in Polyphen		85	106.14	0.80084		1133
Synonymous	-0.154	123	121	1.02	0.00000867	861
Loss of Function	1.98	7	15.4	0.455	6.57e-7	193

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000447	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Converts specific uridines to PSI in a number of tRNA substrates. Acts on positions 27/28 in the anticodon stem and also positions 34 and 36 in the anticodon of an intron containing tRNA. Involved in regulation of nuclear receptor activity through pseudouridylation of SRA1 RNA. {ECO:0000269|PubMed:24722331}.;
Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;tRNA modification in the mitochondrion;Metabolism of RNA;Pyrimidine metabolism (Consensus)

Recessive Scores

pRec: 0.134

Intolerance Scores

loftool: 0.684
rvis_EVS: -0.75
rvis_percentile_EVS: 13.58

Haploinsufficiency Scores

pHI: 0.487
hipred: Y
hipred_score: 0.565
ghis: 0.599

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pus1
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: tRNA pseudouridine synthesis;mitochondrial tRNA pseudouridine synthesis;mRNA pseudouridine synthesis
Cellular component: nucleus;mitochondrion;mitochondrial matrix
Molecular function: tRNA binding;steroid receptor RNA activator RNA binding;RNA binding;pseudouridine synthase activity;tRNA pseudouridine synthase activity