SPIN1

Chr 9

spindlin 1

Also known as: SPIN, TDRD24

The protein mediates lysosomal efflux of lysophospholipids in the phospholipid salvage pathway, which is essential for lysosomal homeostasis and cell survival under nutrient stress. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and progressive neurodegeneration. The gene is highly constrained against loss-of-function variants, indicating that biallelic mutations are likely required for disease.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.27
Clinical SummarySPIN1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.27LOEUF
pLI 0.970
Z-score 3.06
OE 0.00 (0.000.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.25Z-score
OE missense 0.25 (0.190.33)
38 obs / 150.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.27)
00.351.4
Missense OE0.25 (0.190.33)
00.61.4
Synonymous OE0.64
01.21.6
LoF obs/exp: 0 / 10.9Missense obs/exp: 38 / 150.2Syn Z: 2.13
DN
0.2798th %ile
GOF
0.3788th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SPIN1 · 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.

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Clinical Literature
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