STIL

Chr 1AR

STIL centriolar assembly protein

Also known as: MCPH7, SIL

NCBI Gene: 6491 ENSG00000123473 UniProt: Q15468 OMIM: 181590

The protein regulates the mitotic spindle checkpoint by monitoring chromosome segregation during cell division and modulating Cdc2 kinase activity to ensure proper chromosome distribution to daughter cells. Biallelic mutations cause primary microcephaly 7, an autosomal recessive disorder characterized by reduced brain size. The pathogenic mechanism involves disrupted cell division control leading to impaired neuronal proliferation during brain development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a cytoplasmic protein implicated in regulation of the mitotic spindle checkpoint, a regulatory pathway that monitors chromosome segregation during cell division to ensure the proper distribution of chromosomes to daughter cells. The protein is phosphorylated in mitosis and in response to activation of the spindle checkpoint, and disappears when cells transition to G1 phase. It interacts with a mitotic regulator, and its expression is required to efficiently activate the spindle checkpoint. It is proposed to regulate Cdc2 kinase activity during spindle checkpoint arrest. Chromosomal deletions that fuse this gene and the adjacent locus commonly occur in T cell leukemias, and are thought to arise through illegitimate V-(D)-J recombination events. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.381 OMIM phenotype

Clinical Summary— STIL

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Gene-Disease Validity (ClinGen)

autosomal recessive primary microcephaly · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

29 unique Pathogenic / Likely Pathogenic· 258 VUS of 475 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — STIL

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.201

Z-score 5.04

OE 0.24 (0.15–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.13Z-score

OE missense 0.88 (0.82–0.94)

587 obs / 668.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.15–0.38)

0≤0.351.4

Missense OE?0.88 (0.82–0.94)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 12 / 50.8Missense obs/exp: 587 / 668.9Syn Z: 1.54

ClinVar Variant Classifications

475 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic15

VUS258

Likely Benign102

Benign47

Conflicting27

Pathogenic

Likely Pathogenic

258

VUS

102

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	2	1	0	14
Likely Pathogenic	12	2	1	0	15
VUS	3	221	22	12	258
Likely Benign	0	13	38	51	102
Benign	0	3	41	3	47
Conflicting	—				27
Total	26	241	103	66	463

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap STIL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →