ATP1B3

Chr 3

ATPase Na+/K+ transporting subunit beta 3

Also known as: ATPB-3, CD298

NCBI Gene: 483 ENSG00000069849 UniProt: P54709 OMIM: 601867

The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 3 subunit. This gene encodes a beta 3 subunit. A pseudogene exists for this gene, and it is located on chromosome 2. [provided by RefSeq, Jul 2008]

OMIM Research

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

0.68

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.102

Z-score 2.38

OE 0.30 (0.15–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.94Z-score

OE missense 0.55 (0.46–0.66)

81 obs / 147.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.15–0.68)

0≤0.351.4

Missense OE?0.55 (0.46–0.66)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 4 / 13.4Missense obs/exp: 81 / 147.2Syn Z: 0.00

Background carrier burden — how many people carry a rare variant somewhere in ATP1B3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 360

283 rare PASS variants

Rare truncating (LoF)

1 in 6,300

36 rare PASS variants

Rare synonymous (reference)

1 in 410

120 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATP1B3. 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 450	1 in 5,500
South Asian	~43k	1 in 180	1 in 4,400
Remaining (unassigned)	~30k	1 in 340	≈ 1 in 7,500
European (Finnish)	~27k	1 in 1,600	≈ 1 in 26,000
Admixed American	~22k	1 in 360	1 in 2,000
African / African American	~21k	1 in 290	≈ 1 in 7,000
East Asian	~20k	1 in 280	≈ 1 in 6,000
Ashkenazi Jewish	~13k	≈ 1 in 6,400	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 880	≈ 1 in 1,400

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): 6 of 7 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 7.? see exons ↓