MSRA

protein-coding

methionine sulfoxide reductase A

Gene summary

This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

MANE transcript

NM_012331.5

Inheritance

—

ClinVar variants

U:69B:7

Top phenotype

MSRA-related disorder

gnomAD constraint

pLI —, LoF o/e 1.49

Max pathogenic AF

—

Genomic locus

chr8:10,054,292-10,428,891

External References & Databases

Ensembl (ENSG00000175806)

Transcript & Mutation Effects

hg38 • Region Span ~374.6 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 MSRA variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 68

MSRA-related disorderTotal: 6

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012331.5. 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			1 clinvar	3 clinvar		4
missense			66 clinvar	3 clinvar	1 clinvar	70
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	69	6	1	76

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012331.5	RefSeq	NP_036463.1	6	MANE Select
ENST00000317173.9	Ensembl	ENSP00000313921.4	6	MANE Select
NM_001135670.3	RefSeq	NP_001129142.1	5	Standard
NM_001135671.3	RefSeq	NP_001129143.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sulindac Metabolic Pathway
Methionine De Novo and Salvage Pathway
Metabolism of proteins
Protein repair

Biological Process

cellular protein modification process
methionine metabolic process
response to oxidative stress
protein repair
cellular response to oxidative stress

Molecular Function

peptide-methionine (S)-S-oxide reductase activity
L-methionine-(S)-S-oxide reductase activity

Cellular Component

nucleoplasm
cytoplasm
mitochondrion
cytosol
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317173
Coding exons: 6
Length: 374624
Individuals with no LoFs: 125566
Homozygous LoFs: 0
Heterozygous LoFs: 182
Defined: 125748
p: 0.000724

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.63	221	135	1.64	0.00000733	1510
Missense (PolyPhen)		76	53.832	1.4118		610
Synonymous	-3.37	88	56.0	1.57	0.00000357	439
Loss of Function	-1.62	19	12.7	1.49	6.26e-7	145

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00099	0.00092	rare
Latino/Admixed American	0.00062	0.00058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.0013	0.0012	notable
South Asian	0.00027	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.;

Recessive Scores

pRec: 0.337

Intolerance Scores

LoFtool: 0.169
RVIS EVS: -0.96
RVIS percentile EVS: 9.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.507

Gene Damage Prediction

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