SPOUT1

Chr 9AR

SPOUT domain containing methyltransferase 1

ENSG00000198917 UniProt: Q5T280 OMIM: 617614

SPOUT1 encodes an S-adenosyl-L-methionine-dependent RNA methyltransferase that methylates 28S rRNA, maintains centrosome positioning during mitosis, and regulates miRNA processing including MIR145. Mutations cause neurodevelopmental disorders with intellectual disability, seizures, and brain malformations, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

S-adenosyl-L-methionine-dependent RNA methyltransferase (PubMed:39671501, PubMed:39962046). Specifically methylates the N3 position of a uridine in 28S rRNA (PubMed:39671501). Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase, ensuring proper spindle organization (PubMed:20813266, PubMed:25657325, PubMed:39962046). Also involved in chromosome alignment (PubMed:20813266). May promote centrosome maturation probably by recruiting A-kinase anchor protein AKAP9 to centrosomes in early mitosis (PubMed:25657325). Binds specifically to miRNA MIR145 hairpin, regulates MIR145 expression at a postranscriptional level (PubMed:28431233)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with poor growth, seizures, and brain abnormalitiesMIM #621154

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.00

LOEUF

—

Mechanism

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.000

Z-score 1.56

OE 0.67 (0.46–1.00)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.31Z-score

OE missense 0.76 (0.67–0.86)

177 obs / 233.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.46–1.00)

0≤0.351.4

Missense OE?0.76 (0.67–0.86)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 17 / 25.5Missense obs/exp: 177 / 233.2Syn Z: 0.24

Background carrier burden — how many people carry a rare variant somewhere in SPOUT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

486 rare PASS variants

Rare truncating (LoF)

1 in 530

96 rare PASS variants

Rare synonymous (reference)

1 in 210

206 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SPOUT1; this gene does not show strong loss-of-function constraint by this measure. 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)	~556k	1 in 140	1 in 1,000
South Asian	~43k	1 in 130	1 in 1,300
Remaining (unassigned)	~30k	1 in 110	1 in 1,700
European (Finnish)	~27k	1 in 1,100	1 in 2,400
Admixed American	~22k	1 in 190	1 in 1,200
African / African American	~21k	1 in 97	1 in 1,300
East Asian	~20k	1 in 170	1 in 2,500
Ashkenazi Jewish	~13k	1 in 340	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 120	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): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓