NIPA2

Chr 15

NIPA magnesium transporter 2

ENSG00000140157UniProt: Q8N8Q9

Acts as a selective Mg(2+) transporter

329
ClinVar variants
172
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NIPA2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
172 Pathogenic / Likely Pathogenic· 97 VUS of 329 total submissions
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.38LOEUF
pLI 0.921
Z-score 3.02
OE 0.08 (0.03–0.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.22Z-score
OE missense 0.96 (0.85–1.08)
187 obs / 195.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.85–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.31
0≤1.21.6
LoF obs/exp: 1 / 12.5Missense obs/exp: 187 / 195.8Syn Z: -2.11

ClinVar Variant Classifications

329 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic162
Likely Pathogenic10
VUS97
Likely Benign18
Benign36
Conflicting6
162
Pathogenic
10
Likely Pathogenic
97
VUS
18
Likely Benign
36
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
162
0
162
Likely Pathogenic
0
0
10
0
10
VUS
0
50
47
0
97
Likely Benign
0
4
9
5
18
Benign
0
1
33
2
36
Conflicting
—6
Total0552617329

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

View in ClinVar →

Protein Context — Lollipop Plot

NIPA2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prader-Willi Syndrome and Chromosome 15q11.2 BP1-BP2 Region: A Review.
Butler MG·Int J Mol Sci
2023Review
The 15q11.2 BP1-BP2 microdeletion syndrome: a review.
Cox DM et al.·Int J Mol Sci
2015Review
Updated penetrance estimates for recurrent copy number variants - an improved definition and formula.
Goh S et al.·Eur J Hum Genet
2026
Clinical and genetic aspects of the 15q11.2 BP1-BP2 microdeletion disorder.
Butler MG·J Intellect Disabil Res
2017Review
Beyond the Copy Number Differences: The Phenotypic Diversity of Children With 15q11.2 Microdeletions and Microduplications.
Basarir G et al.·J Child Neurol
2025
Clinical features and magnesium levels: Novel insights in 15q11.2 BP1-BP2 copy number variants.
Meossi C et al.·J Intellect Disabil Res
2023
Magnesium Supplement and the 15q11.2 BP1-BP2 Microdeletion (Burnside-Butler) Syndrome: A Potential Treatment?
Butler MG·Int J Mol Sci
2019Review
Familial transmission of recurrent 15q11.2 (BP1-BP2) microdeletion encompassing NIPA1, NIPA2, CYFIP1, and TUBGCP5 associated with phenotypic variability in developmental, speech, and motor delay.
Chen CP et al.·Taiwan J Obstet Gynecol
2017Case report
Advances in genetic mechanisms of hypothalamic dysfunction in Prader-Willi syndrome.
Wang XY et al.·Yi Chuan
2022Review
NIPA2 located in 15q11.2 is mutated in patients with childhood absence epilepsy.
Jiang Y et al.·Hum Genet
2012Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools