NIPA1

Chr 15AD

NIPA magnesium transporter 1

ENSG00000170113UniProt: Q7RTP0

Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Fe(2+), Sr(2+), Ba(2+), Zn(2+) and Co(2+) but to a much less extent than Mg(2+) (By similarity)

Primary Disease Associations & Inheritance

Spastic paraplegia 6, autosomal dominantMIM #600363
AD
590
ClinVar variants
194
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— NIPA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
194 Pathogenic / Likely Pathogenic· 227 VUS of 590 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
Tolerant — LoF & missense variants common in population
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.
1.04LOEUF
pLI 0.006
Z-score 1.49
OE 0.49 (0.26–1.04)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.94Z-score
OE missense 0.60 (0.51–0.70)
110 obs / 184.1 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.0.49 (0.26–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.51–0.70)
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.1.18
0≤1.21.6
LoF obs/exp: 5 / 10.1Missense obs/exp: 110 / 184.1Syn Z: -1.32

ClinVar Variant Classifications

590 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic182
Likely Pathogenic12
VUS227
Likely Benign99
Benign42
Conflicting28
182
Pathogenic
12
Likely Pathogenic
227
VUS
99
Likely Benign
42
Benign
28
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
181
0
182
Likely Pathogenic
0
0
12
0
12
VUS
1
101
122
3
227
Likely Benign
0
1
48
50
99
Benign
0
1
40
1
42
Conflicting
—28
Total110440354590

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

View in ClinVar →

Protein Context — Lollipop Plot

NIPA1 · 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

Spastic paraplegia 6, autosomal dominant

MIM #600363

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — NIPA1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A systematic review and pooled analysis of penetrance estimates of copy-number variants associated with neurodevelopment.
Goh S et al.·Genet Med
2025Review
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
Clinical and genetic characterization of NIPA1 mutations in a Taiwanese cohort with hereditary spastic paraplegia.
Fang SY et al.·Ann Clin Transl Neurol
2023Review
Genetic variability in sporadic amyotrophic lateral sclerosis.
Van Daele SH et al.·Brain
2023
SPG6 (NIPA1 variant): A report of a case with early-onset complex hereditary spastic paraplegia and brief literature review.
Spagnoli C et al.·J Clin Neurosci
2021Review
Updated penetrance estimates for recurrent copy number variants - an improved definition and formula.
Goh S et al.·Eur J Hum Genet
2026
Investigating Repeat Expansions in NIPA1, NOP56, and NOTCH2NLC Genes: A Closer Look at Amyotrophic Lateral Sclerosis Patients from Southern Italy.
Ruffo P et al.·Cells
2024Cohort
The effect of HSP-causing mutations in SPG3A and NIPA1 on the assembly, trafficking, and interaction between atlastin-1 and NIPA1.
Botzolakis EJ et al.·Mol Cell Neurosci
2011
Clinical and genetic aspects of the 15q11.2 BP1-BP2 microdeletion disorder.
Butler MG·J Intellect Disabil Res
2017Review
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