SPIRE1

Chr 18

spire type actin nucleation factor 1

Also known as: Spir-1

NCBI Gene: 56907ENSG00000134278UniProt: Q08AE8

SPIRE1 encodes an actin nucleation factor that organizes the actin cytoskeleton, facilitates intracellular vesicle transport, enables asymmetric cell division during meiosis, and promotes nuclear actin filament assembly for DNA damage repair. Mutations cause autosomal recessive oocyte maturation defect, characterized by female infertility due to impaired meiosis and polar body extrusion. The gene is highly constrained against loss-of-function variants, indicating critical biological importance.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
92
P/LP submissions
0%
P/LP missense
0.46
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SPIRE1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
88 unique Pathogenic / Likely Pathogenic· 97 VUS of 206 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.042
Z-score 4.14
OE 0.27 (0.16–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.47Z-score
OE missense 0.79 (0.71–0.86)
294 obs / 374.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.16–0.46)
0≤0.351.4
Missense OE0.79 (0.71–0.86)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 10 / 37.3Missense obs/exp: 294 / 374.2Syn Z: -0.02
DN
0.6840th %ile
GOF
0.6345th %ile
LOF
0.4627th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

206 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic86
Likely Pathogenic2
VUS97
Likely Benign5
86
Pathogenic
2
Likely Pathogenic
97
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
86
0
86
Likely Pathogenic
0
0
2
0
2
VUS
0
84
13
0
97
Likely Benign
0
3
0
2
5
Benign
0
0
0
0
0
Total0871012190

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

View in ClinVar →

Protein Context — Lollipop Plot

SPIRE1 · 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
Open Research Assistant →
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
Development of proprotein convertase subtilisin/kexin type 9 inhibitors and the clinical potential of monoclonal antibodies in the management of lipid disorders.
Gupta S·Vasc Health Risk Manag
2016Review
Bioinformatic analysis and experimental validation of mitochondria-related genes as novel biomarkers for moyamoya disease.
Yu J et al.·Comput Biol Chem
2026
2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways.
Lloyd-Jones DM et al.·J Am Coll Cardiol
2017Guideline
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.
Schmidt AF et al.·Cochrane Database Syst Rev
2017Meta-analysis
Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy.
Pradhan AD et al.·Circulation
2018
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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