GEMIN8

Chr X

gem nuclear organelle associated protein 8

Also known as: FAM51A1

NCBI Gene: 54960 ENSG00000046647 UniProt: Q9NWZ8

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.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is part of the SMN complex, which is necessary for spliceosomal snRNP assembly in the cytoplasm and pre-mRNA splicing in the nucleus. The encoded protein binds to both SMN1 and the GEMIN6/GEMIN7 heterodimer, mediating their interaction. This protein is found in nuclear Gemini of Cajal bodies (gems) and in the cytoplasm. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.33

Clinical Summary— GEMIN8

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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.

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ClinVar Variants

25 VUS of 59 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.945

Z-score 2.80

OE 0.00 (0.00–0.33)

Highly constrained

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

Missense Constraint?

0.60Z-score

OE missense 0.84 (0.71–1.00)

93 obs / 110.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.33)

0≤0.351.4

Missense OE?0.84 (0.71–1.00)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 0 / 9.1Missense obs/exp: 93 / 110.8Syn Z: 0.31

This gene — mechanism propensity

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

59 submitted variants in ClinVar

ClinVar

Classification Summary

VUS25

Likely Benign7

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	25	0	0	25
Likely Benign	4	0	3	7
Benign	1	1	1	3
Total	30	1	4	35

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap GEMIN8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →