MSRB3

methionine sulfoxide reductase B3

Basic information

Region (hg38): 12:65278643-65491430

Previous symbols: [ "DFNB74" ]

Links

ENSG00000174099 ∙ NCBI:253827 ∙ OMIM:613719 ∙ HGNC:27375 ∙ Uniprot:Q8IXL7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 74 (Strong), mode of inheritance: Unknown
• autosomal recessive nonsyndromic hearing loss 74 (Moderate), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 74 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 74	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	19650862; 21185009

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MSRB3 gene.

• Autosomal recessive nonsyndromic hearing loss 74 (2 variants)
• Hearing loss, autosomal recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MSRB3 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				21	2	23
missense	1		25		1	27
nonsense						0
start loss		1				1
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	3				4
splice region				2	1	3
non coding			3	8	5	16
Total	2	4	29	29	8

Variants in MSRB3

This is a list of pathogenic ClinVar variants found in the MSRB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-65278770-T-C			Conflicting classifications of pathogenicity (Feb 17, 2022)
12-65278770-T-G		Autosomal recessive nonsyndromic hearing loss 74	Likely pathogenic (Aug 04, 2020)
12-65278778-C-A		not specified • MSRB3-related disorder	Benign (Jan 25, 2024)
12-65278787-C-T		Inborn genetic diseases	Uncertain significance (Dec 15, 2023)
12-65278794-GC-G		not specified	Conflicting classifications of pathogenicity (Oct 03, 2023)
12-65278795-C-T			Likely benign (Jan 22, 2024)
12-65278799-C-A		Inborn genetic diseases	Uncertain significance (May 10, 2022)
12-65278799-C-G		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
12-65278799-C-T		not specified	Benign (Oct 08, 2023)
12-65278807-C-T		not specified • MSRB3-related disorder	Likely benign (Jun 01, 2024)
12-65278821-G-A		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
12-65278822-C-T		not specified	Likely benign (Jan 13, 2024)
12-65278841-G-A			Uncertain significance (Sep 04, 2021)
12-65278841-G-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
12-65278842-C-T		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
12-65278850-G-C		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 11, 2023)
12-65278864-C-T			Uncertain significance (Dec 25, 2021)
12-65278873-C-G			Likely benign (Jun 22, 2023)
12-65307027-G-A		Autosomal recessive nonsyndromic hearing loss 74	Uncertain significance (Jan 08, 2020)
12-65308188-C-T			Likely benign (Nov 12, 2018)
12-65308586-G-A			Uncertain significance (May 23, 2023)
12-65308593-A-G			Uncertain significance (Nov 10, 2016)
12-65308594-C-A			Uncertain significance (May 23, 2023)
12-65308634-C-T		Autosomal recessive nonsyndromic hearing loss 74	Pathogenic (Jan 07, 2011)
12-65308662-G-T			Conflicting classifications of pathogenicity (Mar 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MSRB3	protein_coding	protein_coding	ENST00000355192	6	209602

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00377	0.860	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.313	100	109	0.916	0.00000594	1242
Missense in Polyphen		32	44.665	0.71644		521
Synonymous	-0.210	49	47.2	1.04	0.00000302	379
Loss of Function	1.25	5	9.07	0.551	3.83e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000211	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.000109	0.000109
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine. Isoform 2 is essential for hearing. {ECO:0000269|PubMed:14699060, ECO:0000269|PubMed:21185009}.
• Pathway: S-Adenosylhomocysteine (SAH) Hydrolase Deficiency;Methionine Metabolism;Methionine Adenosyltransferase Deficiency;Glycine N-methyltransferase Deficiency;Hypermethioninemia;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type;Cystathionine Beta-Synthase Deficiency;Sulindac Metabolic Pathway;Methionine De Novo and Salvage Pathway;Metabolism of proteins;Protein repair (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.689
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.174
• hipred: Y
• hipred_score: 0.503
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.948

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Msrb3
• Phenotype: cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: msrb3
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein repair;cellular response to oxidative stress;oxidation-reduction process
• Cellular component: mitochondrion;endoplasmic reticulum;cytosol
• Molecular function: protein binding;zinc ion binding;peptide-methionine (R)-S-oxide reductase activity;L-methionine-(R)-S-oxide reductase activity