SPIN1

Chr 9

spindlin 1

Also known as: SPIN, TDRD24

NCBI Gene: 10927ENSG00000106723UniProt: Q9H2V7

Enables histone reader activity and methylated histone binding activity. Involved in positive regulation of DNA-templated transcription; positive regulation of Wnt signaling pathway; and rRNA transcription. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2025]

0
Active trials
27
Pathogenic / LP
40
ClinVar variants
3
Pubs (1 yr)
3.3
Missense Z· constrained
0.27
LOEUF· LoF intolerant
Clinical Summary— SPIN1
⚡
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.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 13 VUS of 40 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

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

Highly LoF-intolerant (top ~10% 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.
3.25Z-score
OE missense 0.25 (0.19–0.33)
38 obs / 150.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.00 (0.00–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.25 (0.19–0.33)
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.0.64
0≤1.21.6
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

40 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic5
VUS13
22
Pathogenic
5
Likely Pathogenic
13
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
5
0
5
VUS
0
9
4
0
13
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0931040

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

View 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Gene expression profiling of SPIN1 in gastric cancer: insights into tumorigenesis and potential therapeutic targets.
Lv BB et al.·Front Genet
2025Open Access
The subcortical maternal complex safeguards mouse oocyte-to-embryo transition by preventing nuclear entry of SPIN1.
Xu C et al.·Nat Struct Mol Biol
2025Functional
Molecular mechanism of interactions of SPIN1 with novel inhibitors through molecular docking and molecular dynamics simulations.
Wang S et al.·SAR QSAR Environ Res
2025Functional
SPIN1 accelerates tumorigenesis and confers radioresistance in non-small cell lung cancer by orchestrating the FOXO3a/FOXM1 axis.
Zhong M et al.·Cell Death Dis
2024Open Access
Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis.
Wang Y et al.·J Mol Cell Biol
2024Open Access
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