SPOUT1

Chr 9

SPOUT domain containing methyltransferase 1

Also known as: C9orf114, CENP-32, CENP32, HSPC109, NEDGSB

NCBI Gene: 51490 ENSG00000198917 UniProt: Q5T280

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.

ResearchSummary from RefSeq, UniProt

Enables miRNA binding activity. Involved in maintenance of centrosome location and miRNA processing. Acts upstream of with a positive effect on post-transcriptional regulation of gene expression. Located in kinetochore; mitotic spindle; and spindle pole centrosome. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

LOEUF 1.00

Clinical Summary— SPOUT1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 36 VUS of 86 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic6

VUS36

Likely Benign9

Benign10

Conflicting2

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	6	0	0	6
VUS	2	33	0	1	36
Likely Benign	1	1	3	4	9
Benign	0	5	1	4	10
Conflicting	—				2
Total	3	45	4	9	63

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap SPOUT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →