STIL

Chr 1AR

STIL centriolar assembly protein

Also known as: MCPH7, SIL

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.381 OMIM phenotype
Clinical SummarySTIL
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Gene-Disease Validity (ClinGen)
autosomal recessive primary microcephaly · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 178 VUS of 300 total submissions
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GeneReview available — STIL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.201
Z-score 5.04
OE 0.24 (0.150.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.13Z-score
OE missense 0.88 (0.820.94)
587 obs / 668.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.150.38)
00.351.4
Missense OE0.88 (0.820.94)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 12 / 50.8Missense obs/exp: 587 / 668.9Syn Z: 1.54

ClinVar Variant Classifications

300 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic14
VUS178
Likely Benign68
Benign23
Conflicting2
7
Pathogenic
14
Likely Pathogenic
178
VUS
68
Likely Benign
23
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
2
0
7
Likely Pathogenic
10
0
4
0
14
VUS
2
169
6
1
178
Likely Benign
0
7
29
32
68
Benign
0
0
23
0
23
Conflicting
2
Total161776433292

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

View in ClinVar →

Protein Context — Lollipop Plot

STIL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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