GEMIN8

Chr X

gem nuclear organelle associated protein 8

Also known as: FAM51A1

NCBI Gene: 54960 ENSG00000046647 UniProt: Q9NWZ8 OMIM: 300962

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.33

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

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

Background carrier burden — how many people carry a rare variant somewhere in GEMIN8?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

201 rare PASS variants

Rare truncating (LoF)

1 in 230,000

1 rare PASS variants

Rare synonymous (reference)

1 in 310

84 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GEMIN8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 600	none seen
South Asian	~36k	1 in 250	≈ 1 in 12,000
Remaining (unassigned)	~31k	1 in 290	none seen
European (Finnish)	~27k	1 in 380	none seen
Admixed American	~23k	1 in 590	none seen
African / African American	~21k	1 in 260	none seen
East Asian	~20k	1 in 280	none seen
Ashkenazi Jewish	~13k	1 in 2,100	none seen
Middle Eastern	~2,758	≈ 1 in 890	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 3.? see exons ↓