SIL1

SIL1 nucleotide exchange factor, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 5:138946723-139293557

Previous symbols: [ "MSS" ]

Links

ENSG00000120725 ∙ NCBI:64374 ∙ OMIM:608005 ∙ HGNC:24624 ∙ Uniprot:Q9H173 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Marinesco-Sjogren syndrome (Definitive), mode of inheritance: AR
• Marinesco-Sjogren syndrome (Strong), mode of inheritance: AR
• Marinesco-Sjogren syndrome (Supportive), mode of inheritance: AR
• Marinesco-Sjogren syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Marinesco-Sjogren syndrome	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	Endocrine; Musculoskeletal; Neurologic; Ophthalmologic	13053231; 830450; 3683758; 10665502; 14512967; 16282978; 16282977; 17309654; 18285827; 20301371; 20111056; 22219183; 23062754

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIL1 gene.

• Marinesco-Sjögren syndrome (248 variants)
• not provided (121 variants)
• not specified (31 variants)
• Inborn genetic diseases (23 variants)
• See cases (1 variants)
• X-linked intellectual disability-short stature-overweight syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIL1 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			6	53	2	61
missense			136	7	2	145
nonsense	4	1	1			6
start loss			2			2
frameshift	9	2				11
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	4				7
splice region			4	5	2	11
non coding		1	14	33	14	62
Total	16	8	160	93	18

Highest pathogenic variant AF is 0.0000920

Variants in SIL1

This is a list of pathogenic ClinVar variants found in the SIL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-138946768-A-G		Marinesco-Sjögren syndrome	Uncertain significance (Jan 12, 2018)
5-138946852-G-C		Marinesco-Sjögren syndrome	Uncertain significance (Jan 12, 2018)
5-138947012-G-A		Marinesco-Sjögren syndrome	Uncertain significance (Jan 12, 2018)
5-138947037-C-G		Marinesco-Sjögren syndrome	Uncertain significance (Jan 13, 2018)
5-138947048-AG-A		Marinesco-Sjögren syndrome	Uncertain significance (Jun 14, 2016)
5-138947087-G-A		Marinesco-Sjögren syndrome	Uncertain significance (Jun 14, 2016)
5-138947123-C-G		Marinesco-Sjögren syndrome	Likely benign (Aug 01, 2022)
5-138947133-A-G		Marinesco-Sjögren syndrome	Pathogenic (Aug 01, 2008)
5-138947135-C-T		Marinesco-Sjögren syndrome	Likely benign (Aug 27, 2023)
5-138947139-C-T		Marinesco-Sjögren syndrome	Uncertain significance (Nov 06, 2019)
5-138947145-A-G		Inborn genetic diseases	Uncertain significance (Mar 17, 2023)
5-138947152-C-T		not specified • Marinesco-Sjögren syndrome • SIL1-related disorder	Benign/Likely benign (Jan 22, 2024)
5-138947156-C-T		Marinesco-Sjögren syndrome	Likely benign (Sep 19, 2023)
5-138947161-C-T		Marinesco-Sjögren syndrome	Uncertain significance (Apr 26, 2023)
5-138947172-C-A		Marinesco-Sjögren syndrome	Uncertain significance (Jul 17, 2022)
5-138947173-C-A		Marinesco-Sjögren syndrome	Uncertain significance (Jun 20, 2023)
5-138947177-G-A		Marinesco-Sjögren syndrome • SIL1-related disorder	Likely benign (Nov 27, 2021)
5-138947182-C-A		Marinesco-Sjögren syndrome	Pathogenic (Jun 17, 2019)
5-138947182-C-T		Marinesco-Sjögren syndrome	Uncertain significance (Aug 15, 2022)
5-138947183-A-G		SIL1-related disorder	Likely benign (Jul 27, 2021)
5-138947186-A-G		Marinesco-Sjögren syndrome	Likely benign (Apr 13, 2023)
5-138947187-T-C		Marinesco-Sjögren syndrome	Uncertain significance (Aug 09, 2022)
5-138947191-G-A		Marinesco-Sjögren syndrome	Pathogenic (Jul 22, 2021)
5-138947217-T-A		Marinesco-Sjögren syndrome • Inborn genetic diseases	Uncertain significance (May 25, 2022)
5-138947221-C-G		Marinesco-Sjögren syndrome	Uncertain significance (Jun 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIL1	protein_coding	protein_coding	ENST00000394817	9	346838

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0123	0.986	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.471	234	255	0.917	0.0000158	2986
Missense in Polyphen		89	95.05	0.93635		1120
Synonymous	-0.636	127	118	1.07	0.00000793	934
Loss of Function	2.79	7	20.7	0.338	9.89e-7	240

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000552	0.0000544
Finnish	0.000835	0.000832
European (Non-Finnish)	0.000328	0.000316
Middle Eastern	0.0000552	0.0000544
South Asian	0.000132	0.000131
Other	0.000862	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5. {ECO:0000269|PubMed:12356756}.
• Disease: DISEASE: Marinesco-Sjoegren syndrome (MSS) [MIM:248800]: Autosomal recessive multisystem disorder which is characterized by cerebellar ataxia due to cerebellar atrophy, with Purkinje and granule cell loss and myopathy featuring marked muscle replacement with fat and connective tissue. Other cardinal features include bilateral cataracts, hypergonadotrophic hypogonadism and mild to severe mental retardation. Skeletal abnormalities, short stature, dysarthria, strabismus and nystagmus are also frequent findings. Mutational inactivation of this protein may result in ER stress- induced cell death signaling or malfunctioning chaperone machineries that mishandle client proteins which are critical for the organs targeted in MSS. {ECO:0000269|PubMed:16282977, ECO:0000269|PubMed:16282978}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.503

Intolerance Scores

• loftool: 0.747
• rvis_EVS: 0.42
• rvis_percentile_EVS: 77.23

Haploinsufficiency Scores

• pHI: 0.0687
• hipred: Y
• hipred_score: 0.504
• ghis: 0.428

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.344

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sil1
• 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: sil1
• Affected structure: Purkinje cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein folding;intracellular protein transport;regulation of catalytic activity
• Cellular component: extracellular space;cytoplasm;endoplasmic reticulum;endoplasmic reticulum lumen
• Molecular function: adenyl-nucleotide exchange factor activity;protein binding;unfolded protein binding