OXSR1

Chr 3

oxidative stress responsive kinase 1

Also known as: OSR1

NCBI Gene: 9943 ENSG00000172939 UniProt: O95747 OMIM: 604046

The OXSR1 protein is a serine/threonine kinase that phosphorylates and regulates ion cotransporters involved in cellular volume control, kidney sodium reabsorption, and response to osmotic stress. Mutations cause autosomal recessive pseudohypoaldosteronism type 2, characterized by hypertension, hyperkalemia, and metabolic acidosis typically presenting in infancy or childhood. The gene is highly constrained against loss-of-function variants (LOEUF 0.368), indicating intolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, UniProt

The product of this gene belongs to the Ser/Thr protein kinase family of proteins. It regulates downstream kinases in response to environmental stress, and may play a role in regulating the actin cytoskeleton. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.37

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.37LOEUF

pLI 0.774

Z-score 4.45

OE 0.20 (0.11–0.37)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.60Z-score

OE missense 0.56 (0.49–0.64)

151 obs / 271.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.20 (0.11–0.37)

0≤0.351.4

Missense OE?0.56 (0.49–0.64)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 7 / 35.7Missense obs/exp: 151 / 271.7Syn Z: -0.76

Background carrier burden — how many people carry a rare variant somewhere in OXSR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

477 rare PASS variants

Rare truncating (LoF)

1 in 5,600

65 rare PASS variants

Rare synonymous (reference)

1 in 260

246 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for OXSR1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 5,400
South Asian	~43k	1 in 140	1 in 6,000
Remaining (unassigned)	~30k	1 in 110	≈ 1 in 30,000
European (Finnish)	~27k	1 in 310	1 in 3,300
Admixed American	~22k	1 in 260	≈ 1 in 9,400
African / African American	~21k	1 in 210	1 in 2,800
East Asian	~20k	1 in 210	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 380	none seen
Middle Eastern	~2,884	1 in 280	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 18 coding exons well covered in gnomAD exomes; exons 2, 3, 5, 6, 7 and 4 more marginal. Genomes: all 18.? see exons ↓