MSRB1

Chr 16

methionine sulfoxide reductase B1

Also known as: HSPC270, SELENOR, SELENOX, SELR, SELX, SEPX1, SepR

NCBI Gene: 51734 ENSG00000198736 UniProt: Q9NZV6 OMIM: 606216

The protein is a selenocysteine-containing methionine-R-sulfoxide reductase that reduces oxidized methionine residues back to methionine, protecting proteins from oxidative damage and regulating actin assembly dynamics. Pathogenic variants in MSRB1 cause autosomal recessive deafness-70, which presents as congenital or early-onset hearing loss. The gene shows relatively low constraint to loss-of-function variation, consistent with its autosomal recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the methionine-R-sulfoxide reductase B (MsrB) family. Members of this family function as repair enzymes that protect proteins from oxidative stress by catalyzing the reduction of methionine-R-sulfoxides to methionines. This protein is highly expressed in liver and kidney, and is localized to the nucleus and cytosol. It is the only member of the MsrB family that is a selenoprotein, containing a selenocysteine (Sec) residue at its active site. It also has the highest methionine-R-sulfoxide reductase activity compared to other members containing cysteine in place of Sec. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. A pseudogene of this locus has been identified on chromosome 19. [provided by RefSeq, Aug 2017]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.13

Clinical Summary— MSRB1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.13) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

25 VUS of 31 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.130

Z-score 1.40

OE 0.36 (0.15–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.12Z-score

OE missense 1.04 (0.86–1.25)

80 obs / 77.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.36 (0.15–1.13)

0≤0.351.4

Missense OE?1.04 (0.86–1.25)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 2 / 5.6Missense obs/exp: 80 / 77.1Syn Z: 0.23

This gene — mechanism propensity

0.6648th %ile

GOF

0.5071th %ile

LOF

0.2582th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

VUS25

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	24	0	25
Likely Benign	0	1	1	2
Benign	0	0	0	0
Total	1	25	1	27

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

39 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap MSRB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →