SPNS1

Chr 16

SPNS lysolipid transporter 1, lysophospholipid

Also known as: HSpin1, LAT, PP2030, SLC62A1, SLC63A1, SPIN1, SPINL, nrs

NCBI Gene: 83985ENSG00000169682UniProt: Q9H2V7

Predicted to enable transmembrane transporter activity. Predicted to be involved in lysophospholipid transport and phospholipid efflux. Predicted to act upstream of or within regulation of lysosomal lumen pH. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

233
ClinVar variants
114
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— SPNS1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
114 Pathogenic / Likely Pathogenic· 89 VUS of 233 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.60LOEUF
pLI 0.020
Z-score 2.97
OE 0.32 (0.18–0.60)
Moderately 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.
2.06Z-score
OE missense 0.69 (0.62–0.77)
237 obs / 344.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.32 (0.18–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.62–0.77)
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.0.92
0≤1.21.6
LoF obs/exp: 7 / 22.1Missense obs/exp: 237 / 344.4Syn Z: 0.80

ClinVar Variant Classifications

233 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic104
Likely Pathogenic10
VUS89
Likely Benign7
Benign1
Conflicting2
104
Pathogenic
10
Likely Pathogenic
89
VUS
7
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
104
0
104
Likely Pathogenic
0
0
10
0
10
VUS
1
53
35
0
89
Likely Benign
0
3
1
3
7
Benign
0
0
0
1
1
Conflicting
—2
Total1561504213

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

View in ClinVar →

Protein Context — Lollipop Plot

SPNS1 · 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
Lack of SPNS1 results in accumulation of lysolipids and lysosomal storage disease in mouse models.
Ha HT et al.·JCI Insight
2024Functional
Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1.
Yang X et al.·Biomed Pharmacother
2024
Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.
Luce A et al.·J Transl Med
2025
Role of autophagy-related genes in liver cancer prognosis.
Zhou Y et al.·Genomics
2024
A systematic heritability analysis of the human whole blood transcriptome.
Huan T et al.·Hum Genet
2015
Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD.
Kanoni S et al.·Front Immunol
2021Cohort
Identification of an autophagy-related gene signature that can improve prognosis of hepatocellular carcinoma patients.
Huo X et al.·BMC Cancer
2020Cohort
ATIC inhibits autophagy in hepatocellular cancer through the AKT/FOXO3 pathway and serves as a prognostic signature for modeling patient survival.
Zhang H et al.·Int J Biol Sci
2021Functional
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