SIL1 (SIL1 nucleotide exchange factor)

Gene

• Entrez ID: 64374
• Gene name: SIL1 nucleotide exchange factor
• Gene symbol: SIL1
• Synonyms (NCBI Gene): BAP, MSS, ULG5
• Chromosome: 5
• Chromosome location: 5q31.2
• Summary: This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for ano

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs115800498	G>A	Benign-likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs119456966	G>A	Pathogenic	Stop gained, coding sequence variant
rs148927511	C>T	Conflicting-interpretations-of-pathogenicity, benign-likely-benign	Coding sequence variant, synonymous variant
rs199890503	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs368666457	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs370290043	C>A,T	Pathogenic	Intron variant
rs372816951	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs774441811	G>A	Pathogenic	Coding sequence variant, stop gained
rs886043087	C>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT040372	hsa-miR-615-3p	CLASH	23622248
MIRT1349409	hsa-miR-1343	CLIP-seq
MIRT1349410	hsa-miR-146b-3p	CLIP-seq
MIRT1349411	hsa-miR-3074-5p	CLIP-seq
MIRT1349412	hsa-miR-3173-5p	CLIP-seq
MIRT1349413	hsa-miR-3690	CLIP-seq
MIRT1349414	hsa-miR-4254	CLIP-seq
MIRT1349415	hsa-miR-4308	CLIP-seq
MIRT1349416	hsa-miR-4326	CLIP-seq
MIRT1349417	hsa-miR-4722-3p	CLIP-seq
MIRT1349418	hsa-miR-874	CLIP-seq
MIRT2103532	hsa-miR-1245b-3p	CLIP-seq
MIRT2103533	hsa-miR-3660	CLIP-seq
MIRT2103534	hsa-miR-3915	CLIP-seq
MIRT2103535	hsa-miR-3928	CLIP-seq
MIRT2103536	hsa-miR-4261	CLIP-seq
MIRT2103537	hsa-miR-4496	CLIP-seq
MIRT2103538	hsa-miR-4526	CLIP-seq
MIRT2103539	hsa-miR-483-3p	CLIP-seq
MIRT2103532	hsa-miR-1245b-3p	CLIP-seq
MIRT2103533	hsa-miR-3660	CLIP-seq
MIRT2103534	hsa-miR-3915	CLIP-seq
MIRT2103535	hsa-miR-3928	CLIP-seq
MIRT2103536	hsa-miR-4261	CLIP-seq
MIRT2103537	hsa-miR-4496	CLIP-seq
MIRT2103538	hsa-miR-4526	CLIP-seq
MIRT2622798	hsa-miR-1910	CLIP-seq
MIRT2622799	hsa-miR-324-5p	CLIP-seq
MIRT2622800	hsa-miR-455-3p	CLIP-seq
MIRT2622799	hsa-miR-324-5p	CLIP-seq
MIRT2622800	hsa-miR-455-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000774	Function	Adenyl-nucleotide exchange factor activity	IBA
GO:0000774	Function	Adenyl-nucleotide exchange factor activity	IDA	12356756
GO:0005515	Function	Protein binding	IPI	12356756, 24473200, 25416956, 28514442, 31258504, 32296183, 33961781
GO:0005615	Component	Extracellular space	HDA	16502470
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IDA	12356756
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005783	Component	Endoplasmic reticulum	NAS	11101517
GO:0005788	Component	Endoplasmic reticulum lumen	IEA
GO:0006457	Process	Protein folding	NAS	11101517
GO:0006613	Process	Cotranslational protein targeting to membrane	ISS
GO:0006886	Process	Intracellular protein transport	NAS	11101517
GO:0015031	Process	Protein transport	IEA
GO:0042802	Function	Identical protein binding	IPI	31258504
GO:0051082	Function	Unfolded protein binding	NAS	11101517

Other IDs

• MIM: 608005
• HGNC: 24624
• e!Ensembl: ENSG00000120725

Protein

• UniProt ID: Q9H173
• Protein name: Nucleotide exchange factor SIL1 (BiP-associated protein) (BAP)
• Protein function: Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5.
• PDB: 6LBN, 6LEY, 8PQL, 8Q7R
• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in tissues which produce large amounts of secreted proteins such as kidney, liver and placenta. Also expressed in colon, heart, lung, ovary, pancreas, peripheral leukocyte, prostate, spleen and thymus. Expressed at low
• Sequence:

  MAPQSLPSSRMAPLGMLLGLLMAACFTFCLSHQNLKEFALTNPEKSSTKETERKETKAEE
  ELDAEVLEVFHPTHEWQALQPGQAVPAGSHVRLNLQTGEREAKLQYEDKFRNNLKGKRLD
  INTNTYTSQDLKSALAKFKEGAEMESSKEDKARQAEVKRLFRPIEELKKDFDELNVVIET
  DMQIMVRLINKFNSSSSSLEEKIAALFDLEYYVHQMDNAQDLLSFGGLQVVINGLNSTEP
  LVKEYAAFVLGAAFSSNPKVQVEAIEGGALQKLLVILATEQPLTAKKKVLFALCSLLRHF
  PYAQRQFLKLGGLQVLRTLVQEKGTEVLAVRVVTLLYDLVTEKMFAEEEAELTQEMSPEK
  LQQYRQVHLLPGLWEQGWCEITAHLLALPEHDAREKVLQTLGVLLTTCRDRYRQDPQLGR
  TLASLQAEYQVLASLELQDGEDEGYFQELLGSVNSLLKELR

• Sequence length: 461

Pathways

KEGG:

Protein processing in endoplasmic reticulum

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
	Pathogenic; Likely pathogenic	rs779649580, rs1561799392, rs2546366412, rs1768517145, rs751236516, rs794726659, rs548535414, rs119456965, rs777752978, rs119456966, rs119456967, rs587776544, rs869320725, rs2546421783, rs2546421757, rs749423210, rs2534009524, rs2546345169, rs2534009501, rs368867955, rs370290043, rs2546340450, rs767943814, rs1355037102	RCV001329282 RCV001384264 RCV002031734 RCV002284294 RCV000002740 RCV000002741 RCV000002742 RCV000002743 RCV000002744 RCV000002745 RCV000002746 RCV000002747 RCV000002748 RCV002571532 RCV002875663 RCV002947280 RCV002932939 RCV002998997 RCV003013251 RCV003123521 RCV003134012 RCV001782768 RCV003606213 RCV000778754 RCV000987604	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
APRAXIAS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BLEPHAROPTOSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CATARACT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CEREBELLAR ATROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLOBAL DEVELOPMENTAL DELAY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MARINESCO-SJOGREN SYNDROME	—	CTD, ClinGen, Disgenet, HPO CTD, ClinGen, Disgenet, HPO CTD, ClinGen, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SIL1-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STRABISMUS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-linked intellectual disability-short stature-overweight syndrome	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired cubitus valgus	Cubitus valgus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	25559081, 28401474		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	27896942		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	27896942		★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	24176978, 34830330	Associate	★☆☆☆☆ Found in Text Mining only
Ataxias, Hereditary	Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	30471191		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL SEPTAL DEFECT 1	Atrial Septal Defect	BEFREE	30488153		★☆☆☆☆ Found in Text Mining only
Atrial Septal Defects	Atrial Septal Defect	BEFREE	30488153		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	25432440, 27896942, 30488153, 30974902		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	30974902		★☆☆☆☆ Found in Text Mining only
Avascular necrosis of the capital femoral epiphysis	Avascular Necrosis Of The Capital Femoral Epiphysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	27915435, 31791191		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	Pubtator	24176978, 24755310	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cataract	Cataract	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cerebellar Ataxia, Early Onset	Cerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Ataxia, Late Onset	Cerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	BEFREE	25958341		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cerebellar cortical atrophy	Cerebellar cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Degenerations, Primary	Cerebellar Degenerations	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar Diseases	BEFREE	24176978		★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	24176978	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar Hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cervical lymphadenopathy	Cervical lymphadenopathy	BEFREE	15472315		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	28646624		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	24176978	Associate	★☆☆☆☆ Found in Text Mining only
Congenital pectus carinatum	Congenital Pectus Carinatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Corticostriatal-Spinal Degeneration	Corticostriatal-Spinal Degeneration	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Dandy-Walker Syndrome	Dandy-Walker Syndrome	BEFREE	27106665		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	31834482		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	29997438		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	29997438		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	24176978, 31531014		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Legg-Calve-Perthes Disease	Legg-Calve-Perthes Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31791191		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	CTD_human_DG	17013881		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	9562963		★☆☆☆☆ Found in Text Mining only
Marie Cerebellar Ataxia	Marie Cerebellar Ataxia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Marinesco-Sjogren syndrome	Marinesco-Sjogren Syndrome	GENOMICS_ENGLAND_DG	11528383, 16282977, 24176978, 25929793		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Marinesco-Sjogren syndrome	Marinesco-Sjogren Syndrome	BEFREE	16282977, 16282978, 16962589, 18285827, 18395226, 20111056, 21873089, 22115007, 22219183, 23062754, 24176978, 24473200, 24631270, 24755310, 25473114, 25559081, 26260654, 27106665, 27544240, 28257000, 28978133, 29406913, 29718201, 29997438, 30293566, 30468864, 31258504, 31531014, 31701543		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Marinesco-Sjogren syndrome	Marinesco-Sjogren Syndrome	ORPHANET_DG	16650075		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Marinesco-Sjogren syndrome	Marinesco-Sjogren Syndrome	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Marinesco-Sjogren syndrome	Marinesco-Sjogren Syndrome	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
	Marinesco-Sjogren Syndrome	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
melanoma	Melanoma	BEFREE	29058705		★☆☆☆☆ Found in Text Mining only
Mental Retardation	Mental retardation	BEFREE	31531014		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	30293566	Associate	★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	BEFREE	25958341		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	3874450, 6162924, 7438496, 93633		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy	Muscular dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	16282977, 24176978, 29666155, 29718201		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29752733		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	28401474		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polycystic liver disease	Polycystic liver disease	BEFREE	17071140		★☆☆☆☆ Found in Text Mining only
Primary hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	CTD_human_DG	17013881		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Specific learning disability	Specific Learning Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spinocerebellar Degeneration	Spinocerebellar Degeneration	LHGDN	16282977, 18285827		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Degeneration	Spinocerebellar Degeneration	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Uveal Melanoma	BEFREE	31146482		★☆☆☆☆ Found in Text Mining only
Vacuolar myopathy	Vacuolar myopathy	Pubtator	21873089	Associate	★☆☆☆☆ Found in Text Mining only