STIL

STIL centriolar assembly protein

Basic information

Region (hg38): 1:47250138-47314892

Previous symbols: [ "SIL" ]

Links

ENSG00000123473 ∙ NCBI:6491 ∙ OMIM:181590 ∙ HGNC:10879 ∙ Uniprot:Q15468 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly 7, primary, autosomal recessive (Strong), mode of inheritance: AR
• microcephaly 7, primary, autosomal recessive (Strong), mode of inheritance: AR
• holoprosencephaly (Supportive), mode of inheritance: AR
• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
• autosomal recessive primary microcephaly (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, primary autosomal recessive, 7	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	19215732; 20978018; 25218063

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STIL gene.

• not provided (215 variants)
• Microcephaly 7, primary, autosomal recessive (117 variants)
• Inborn genetic diseases (42 variants)
• not specified (34 variants)
• Primary Microcephaly, Recessive (3 variants)
• Abnormal brain morphology (2 variants)
• STIL-related condition (2 variants)
• Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STIL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	35	3	50
missense		2	135	7	3	147
nonsense	1	2	1			4
start loss						0
frameshift	3	5	3			11
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	1				2
splice region		1	5			6
non coding			14	32	42	88
Total	5	10	167	74	48

Highest pathogenic variant AF is 0.0000197

Variants in STIL

This is a list of pathogenic ClinVar variants found in the STIL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-47250144-T-C		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Jan 12, 2018)
1-47250158-A-G		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
1-47250251-G-A		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
1-47250253-T-C		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
1-47250368-TAA-T		Primary Microcephaly, Recessive	Benign (Jun 14, 2016)
1-47250406-T-C		Microcephaly 7, primary, autosomal recessive	Likely benign (Jan 13, 2018)
1-47250537-T-C		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
1-47250559-C-T		Microcephaly 7, primary, autosomal recessive	Benign (Jan 12, 2018)
1-47250591-G-A		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
1-47250820-A-G		Microcephaly 7, primary, autosomal recessive	Benign (Jan 12, 2018)
1-47250884-T-C		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Jan 13, 2018)
1-47250933-G-A		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Jan 12, 2018)
1-47251134-G-A		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Apr 27, 2017)
1-47251164-C-T		Microcephaly 7, primary, autosomal recessive	Uncertain significance (Dec 02, 2021)
1-47251165-G-A		Microcephaly 7, primary, autosomal recessive	Conflicting classifications of pathogenicity (Nov 10, 2023)
1-47251167-T-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
1-47251217-C-T		not specified • Microcephaly 7, primary, autosomal recessive	Benign/Likely benign (Jan 29, 2024)
1-47251249-T-C		not specified • Microcephaly 7, primary, autosomal recessive	Uncertain significance (Aug 01, 2020)
1-47251251-G-A			Uncertain significance (Jan 12, 2021)
1-47251253-A-T			Likely benign (Nov 05, 2018)
1-47251285-G-A		Microcephaly 7, primary, autosomal recessive	Pathogenic (Feb 01, 2009)
1-47251289-G-A			Uncertain significance (Nov 12, 2013)
1-47251304-G-A		Microcephaly 7, primary, autosomal recessive	Conflicting classifications of pathogenicity (Aug 30, 2023)
1-47251308-C-T			Uncertain significance (Jun 29, 2022)
1-47251344-AC-A		Microcephaly 7, primary, autosomal recessive	Pathogenic (Feb 01, 2009)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STIL	protein_coding	protein_coding	ENST00000371877	16	64009

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.201	0.799	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	587	669	0.878	0.0000329	8535
Missense in Polyphen		159	193.5	0.8217		2479
Synonymous	1.54	210	240	0.874	0.0000127	2438
Loss of Function	5.04	12	50.8	0.236	0.00000253	669

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000969	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 (PubMed:16024801, PubMed:9372240). Plays an important role in the regulation of centriole duplication. Required for the onset of procentriole formation and proper mitotic progression. During procentriole formation, is essential for the correct loading of SASS6 and CENPJ to the base of the procentriole to initiate procentriole assembly (PubMed:22020124). {ECO:0000269|PubMed:16024801, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:9372240}.
• Disease: DISEASE: Note=A chromosomal aberration involving STIL may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). A deletion at 1p32 between STIL and TAL1 genes leads to STIL/TAL1 fusion mRNA with STIL exon 1 splicing to TAL1 exon 3. As both STIL exon 1 and TAL1 exon 3 are 5'-untranslated exons, STIL/TAL1 fusion mRNA predicts a full-length TAL1 protein under the control of the STIL promoter, leading to inappropriate TAL1 expression. In childhood T-cell malignancies (T-ALL), a type of defect such as STIL/TAL1 fusion is associated with a good prognosis. In cultured lymphocytes from healthy adults, STIL/TAL1 fusion mRNA may be detected after 7 days of culture. {ECO:0000269|PubMed:11390401, ECO:0000269|PubMed:12681356, ECO:0000269|PubMed:1311214, ECO:0000269|PubMed:14504110, ECO:0000269|PubMed:1922059, ECO:0000269|PubMed:2209547, ECO:0000269|PubMed:2255914}.; DISEASE: Microcephaly 7, primary, autosomal recessive (MCPH7) [MIM:612703]: A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. {ECO:0000269|PubMed:19215732, ECO:0000269|PubMed:22989186}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling events mediated by the Hedgehog family (Consensus)

Recessive Scores

• pRec: 0.0886

Intolerance Scores

• loftool: 0.754
• rvis_EVS: 0.69
• rvis_percentile_EVS: 85.29

Haploinsufficiency Scores

• pHI: 0.342
• hipred: N
• hipred_score: 0.233
• ghis: 0.588

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0797

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Stil
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo phenotype; growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype

Zebrafish Information Network

• Gene name: stil
• Affected structure: cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: embryonic axis specification;in utero embryonic development;neural tube closure;heart looping;mitotic spindle organization;smoothened signaling pathway;determination of left/right symmetry;cell population proliferation;neural tube development;forebrain development;notochord development;floor plate development;multicellular organism growth;negative regulation of apoptotic process;regulation of centriole replication;centrosome duplication;protein localization to centrosome
• Cellular component: cytoplasm;centrosome;centriole;cytosol
• Molecular function: protein binding;identical protein binding