GEMIN8

Chr X

gem nuclear organelle associated protein 8

Also known as: FAM51A1

The protein is a component of the SMN complex that catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), which are essential building blocks of the spliceosome required for pre-mRNA splicing. GEMIN8 mutations cause spinal muscular atrophy with respiratory distress type 1, an autosomal recessive neuromuscular disorder with onset in infancy. The gene is highly constrained against loss-of-function variants, indicating critical importance for normal cellular function.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.33
Clinical SummaryGEMIN8
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
70 unique Pathogenic / Likely Pathogenic· 29 VUS of 133 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.945
Z-score 2.80
OE 0.00 (0.000.33)
Highly constrained

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

Missense Constraint
0.60Z-score
OE missense 0.84 (0.711.00)
93 obs / 110.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.33)
00.351.4
Missense OE0.84 (0.711.00)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 0 / 9.1Missense obs/exp: 93 / 110.8Syn Z: 0.31
DN
0.3594th %ile
GOF
0.3094th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.33

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

133 submitted variants in ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic1
VUS29
Likely Benign7
Benign3
69
Pathogenic
1
Likely Pathogenic
29
VUS
7
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
69
0
69
Likely Pathogenic
0
0
1
0
1
VUS
0
25
4
0
29
Likely Benign
0
4
0
3
7
Benign
0
1
1
1
3
Total030754109

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

View in ClinVar →

Protein Context — Lollipop Plot

GEMIN8 · 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.

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 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC