ATP1B2

Chr 17

ATPase Na+/K+ transporting subunit beta 2

Also known as: AMOG

NCBI Gene: 482 ENSG00000129244 UniProt: P14415 OMIM: 182331

The ATP1B2 protein is the beta-2 subunit of the Na+/K+-ATPase pump, which regulates the number of sodium pumps transported to the plasma membrane and is essential for maintaining electrochemical gradients across cell membranes that support nerve and muscle excitability. Mutations cause autosomal recessive epilepsy and developmental delay, with this gene showing moderate constraint against loss-of-function variants (LOEUF 0.624). The condition primarily affects the nervous system with seizures typically beginning in infancy or early childhood.

OMIM ResearchSummary from RefSeq, UniProt

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 2 subunit. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.62

Clinical Summary— ATP1B2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

41 VUS of 47 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.074

Z-score 2.67

OE 0.30 (0.15–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.82Z-score

OE missense 0.83 (0.73–0.95)

155 obs / 186.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.15–0.62)

0≤0.351.4

Missense OE?0.83 (0.73–0.95)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 5 / 16.8Missense obs/exp: 155 / 186.4Syn Z: 0.26

This gene — mechanism propensity

0.6551th %ile

GOF

0.5954th %ile

LOF

0.2777th %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

47 submitted variants in ClinVar

ClinVar

Classification Summary

VUS41

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	41	41
Likely Benign	0	0
Benign	0	0
Total	41	41

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap ATP1B2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →