TSR2

protein-coding

TSR2 ribosome maturation factor, the group of Ribosomal biogenesis factors

Gene summary

The protein encoded by this gene appears to repress the transcription of NF-kappaB and may be involved in apoptosis. Defects in this gene are a cause of Diamond-Blackfan anemia. [provided by RefSeq, Oct 2016]

MANE transcript

NM_058163.3

Inheritance

XL, AD

ClinVar variants

P:1U:69B:16

Top phenotype

Diamond-Blackfan anemia 14 with mandibulofacial dysostosis

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:54,440,404-54,448,032

External References & Databases

Ensembl (ENSG00000158526)

Transcript & Mutation Effects

hg38 • Region Span ~7.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Diamond-Blackfan anemia 14 with mandibulofacial dysostosisLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010493

Submitter: Ambry Genetics

Diamond-Blackfan anemia 14 with mandibulofacial dysostosisLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010493

Submitter: Labcorp Genetics (formerly Invitae)

Diamond-Blackfan anemiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015253

Submitter: Orphanet

Diamond-Blackfan anemia 14 with mandibulofacial dysostosisLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010493

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Diamond-Blackfan anemia 14 with mandibulofacial dysostosisXL

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Oncologic

Intervention: Audiologic/Otolaryngologic; Hematologic; Oncologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management

Refs: 11424144; 24942156

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TSR2 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 51

not specifiedTotal: 19

TSR2-related disorderTotal: 6

Diamond-Blackfan anemia 14 with mandibulofacial dysostosisTotal: 2

Diamond-Blackfan anemia 15 with mandibulofacial dysostosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_058163.3. 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			7 clinvar	14 clinvar	1 clinvar	22
missense	1 clinvar		48 clinvar		1 clinvar	50
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	1	0	69	14	2	86

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_058163.3	RefSeq	NP_477511.1	5	MANE Select
ENST00000375151.5	Ensembl	ENSP00000364293.4	5	MANE Select
NM_001346789.2	RefSeq	NP_001333718.1	5	Standard
NM_001346790.2	RefSeq	NP_001333719.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tsr2	Danio rerio	Structure: ceratohyal cartilage Quality: bent abnormal

Gene / Model

Organism

Observed Phenotype

tsr2

Danio rerio

Structure: ceratohyal cartilage

Quality: bent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)

Molecular Function

protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375151
Coding exons: 5
Length: 5087
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.989	44	66.7	0.659	0.00000465	1259
Missense (PolyPhen)		5	14.73	0.33943		284
Synonymous	-0.635	30	25.9	1.16	0.00000197	362
Loss of Function	2.14	0	5.34	0.00	3.37e-7	99

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in 20S pre-rRNA processing. {ECO:0000305}.;
Disease: DISEASE: Diamond-Blackfan anemia 14, with mandibulofacial dysostosis (DBA14) [MIM:300946]: A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. {ECO:0000269|PubMed:24942156}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.109

Intolerance Scores

RVIS EVS: 0.01
RVIS percentile EVS: 54.63

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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