TRUB2

protein-coding

TruB pseudouridine synthase family member 2, the group of Pseudouridine synthases

Gene summary

Pseudouridine is an abundant component of rRNAs and tRNAs and is enzymatically generated by isomerization of uridine by pseudouridine synthase (Zucchini et al., 2003 [PubMed 12736709]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_015679.3

Inheritance

—

ClinVar variants

U:73B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr9:128,305,159-128,322,447

External References & Databases

Ensembl (ENSG00000167112)

Transcript & Mutation Effects

hg38 • Region Span ~17.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRUB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015679.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			69 clinvar	2 clinvar		71
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	73	4	0	77

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015679.3	RefSeq	NP_056494.1	8	MANE Select
ENST00000372890.6	Ensembl	ENSP00000361982.4	8	MANE Select
NM_001329861.2	RefSeq	NP_001316790.1	7	Standard
NM_001329862.2	RefSeq	NP_001316791.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

pseudouridine synthesis
mRNA processing
positive regulation of mitochondrial translation

Molecular Function

RNA binding
protein binding
pseudouridine synthase activity

Cellular Component

mitochondrial matrix
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372890
Coding exons: 8
Length: 13640
Individuals with no LoFs: 125448
Homozygous LoFs: 0
Heterozygous LoFs: 300
Defined: 125748
p: 0.00119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0468	209	211	0.991	0.0000130	2120
Missense (PolyPhen)		61	70.804	0.86153		698
Synonymous	-0.879	102	91.3	1.12	0.00000591	706
Loss of Function	0.906	10	13.6	0.735	6.60e-7	163

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00058	0.00058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.0012	0.0012	notable
European (Non-Finnish)	0.0020	0.0020	notable
South Asian	0.00042	0.00042	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Minor enzyme contributing to the isomerization of uridine to pseudouridine (pseudouridylation) of specific mitochondrial mRNAs (mt-mRNAs) such as COXI and COXIII mt-mRNAs (PubMed:27974379). As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation (PubMed:27667664). {ECO:0000269|PubMed:27667664, ECO:0000269|PubMed:27974379}.;

Recessive Scores

pRec: 0.0880

Intolerance Scores

LoFtool: 0.836
RVIS EVS: 0.44
RVIS percentile EVS: 77.91

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.926

Gene Damage Prediction

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