ATP1B2

Chr 17

ATPase Na+/K+ transporting subunit beta 2

Also known as: AMOG

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.62
Clinical SummaryATP1B2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 49 VUS of 75 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.62LOEUF
pLI 0.074
Z-score 2.67
OE 0.30 (0.150.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.82Z-score
OE missense 0.83 (0.730.95)
155 obs / 186.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.150.62)
00.351.4
Missense OE0.83 (0.730.95)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 5 / 16.8Missense obs/exp: 155 / 186.4Syn Z: 0.26
DN
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

75 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS49
19
Pathogenic
1
Likely Pathogenic
49
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
41
8
0
49
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total04128069

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

View in ClinVar →

Protein Context — Lollipop Plot

ATP1B2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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