TSR2

TSR2 ribosome maturation factor, the group of Ribosomal biogenesis factors

Basic information

Region (hg38): X:54440404-54448032

Links

ENSG00000158526 ∙ NCBI:90121 ∙ OMIM:300945 ∙ HGNC:25455 ∙ Uniprot:Q969E8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Diamond-Blackfan anemia (Supportive), mode of inheritance: AD
• Diamond-Blackfan anemia 14 with mandibulofacial dysostosis (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diamond-Blackfan anemia 14 with mandibulofacial dysostosis	XL	Audiologic/Otolaryngologic; Hematologic; Oncologic	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	Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Oncologic	11424144; 24942156

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TSR2 gene.

• Diamond-Blackfan anemia 15 with mandibulofacial dysostosis (1 variants)
• not provided (1 variants)
• Diamond-Blackfan anemia 14 with mandibulofacial dysostosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSR2 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			6	4	1	11
missense	1		20		1	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3			3
non coding	1	6	32	27	6	72
Total	2	6	58	31	8

Variants in TSR2

This is a list of pathogenic ClinVar variants found in the TSR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-54440428-G-A			Uncertain significance (Aug 24, 2022)
X-54440433-T-C		TSR2-related disorder	Likely benign (Jan 23, 2025)
X-54440435-C-T		not specified	Uncertain significance (Jul 19, 2022)
X-54440438-A-G		TSR2-related disorder	Uncertain significance (Oct 05, 2022)
X-54440443-G-C		not specified	Uncertain significance (Nov 10, 2024)
X-54440446-C-A			Uncertain significance (Jun 26, 2023)
X-54440466-G-T			Uncertain significance (Oct 24, 2022)
X-54440482-G-C		not specified	Uncertain significance (Aug 22, 2023)
X-54440509-G-GGGGCCA			Likely benign (May 28, 2024)
X-54440522-G-A			Likely benign (Jul 01, 2024)
X-54440632-C-T			Benign (May 22, 2021)
X-54440690-A-G			Uncertain significance (Nov 07, 2023)
X-54440712-G-C			Uncertain significance (Jan 22, 2025)
X-54440746-G-C			Uncertain significance (Aug 04, 2023)
X-54440751-G-A			Benign (Oct 06, 2023)
X-54440774-C-A			Uncertain significance (Oct 01, 2023)
X-54440774-C-T		not specified	Uncertain significance (Oct 30, 2024)
X-54440775-G-T			Uncertain significance (Oct 22, 2024)
X-54440776-C-G			Uncertain significance (Sep 19, 2023)
X-54440783-G-A			Uncertain significance (Nov 14, 2024)
X-54440800-C-A			Likely benign (Jun 22, 2024)
X-54443382-C-G			Likely benign (Nov 02, 2024)
X-54443394-A-G			Likely benign (Dec 02, 2024)
X-54443414-G-C			Uncertain significance (May 21, 2023)
X-54443418-A-G		Diamond-Blackfan anemia 14 with mandibulofacial dysostosis • Diamond-Blackfan anemia 15 with mandibulofacial dysostosis	Pathogenic (May 19, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSR2	protein_coding	protein_coding	ENST00000375151	5	5087

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.801	0.194	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.989	44	66.7	0.659	0.00000465	1259
Missense in 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

LoF frequencies by population

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

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.115
• hipred: N
• hipred_score: 0.335
• ghis: 0.605

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tsr2

Zebrafish Information Network

• Gene name: tsr2
• Affected structure: ceratohyal cartilage
• Phenotype tag: abnormal
• Phenotype quality: bent

Gene ontology

• Biological process: maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)
• Molecular function: protein binding