ATP9B

Chr 18

ATPase phospholipid transporting 9B

Also known as: ATPASEP, ATPIIB, HUSSY-20, NEO1L, hMMR1

NCBI Gene: 374868ENSG00000166377UniProt: O43861

ATP9B encodes an ATPase that transports lipids across intracellular membranes and is involved in endocytosis and vesicle transport between the Golgi and endoplasmic reticulum. Mutations cause autosomal recessive intellectual disability with hypotonia and behavioral abnormalities. The gene is highly constrained against loss-of-function variants in the population.

Summary from RefSeq
Research Assistant →
0
Active trials
2
Pubs (1 yr)
143
P/LP submissions
0%
P/LP missense
0.69
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ATP9B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
142 unique Pathogenic / Likely Pathogenic· 192 VUS of 399 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
0.69LOEUF
pLI 0.000
Z-score 3.63
OE 0.52 (0.39–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.69Z-score
OE missense 0.93 (0.87–0.99)
634 obs / 684.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.39–0.69)
0≤0.351.4
Missense OE0.93 (0.87–0.99)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 34 / 65.7Missense obs/exp: 634 / 684.9Syn Z: -0.36
DN
0.7130th %ile
GOF
0.74top 25%
LOF
0.2777th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

399 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic135
Likely Pathogenic7
VUS192
Likely Benign15
Benign5
135
Pathogenic
7
Likely Pathogenic
192
VUS
15
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
135
0
135
Likely Pathogenic
0
0
7
0
7
VUS
0
170
22
0
192
Likely Benign
0
6
5
4
15
Benign
0
1
1
3
5
Total01771707354

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

View in ClinVar →

Protein Context — Lollipop Plot

ATP9B · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients