SIL1

Chr 5AR

SIL1 nucleotide exchange factor

Also known as: BAP, MSS, ULG5

NCBI Gene: 64374ENSG00000120725UniProt: Q9H173

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 another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Marinesco-Sjogren syndromeMIM #248800
AR
UniProtMarinesco-Sjoegren syndrome
460
ClinVar variants
0
Pathogenic / LP
0.01
pLI score
1
Active trials
Clinical Summary— SIL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
460 total variants — no pathogenic classifications of 460 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.64LOEUF
pLI 0.012
Z-score 2.79
OE 0.34 (0.19–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.47Z-score
OE missense 0.92 (0.82–1.02)
234 obs / 255.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.34 (0.19–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.82–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 7 / 20.7Missense obs/exp: 234 / 255.2Syn Z: -0.64

ClinVar Variant Classifications

460 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

SIL1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SIL1-related Marinesco-Sjoegren syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Marinesco-Sjogren syndrome

MIM #248800

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Ceramic laminate veneers: effect of preparation design and ceramic thickness on fracture resistance and marginal quality in vitro.
Blunck U et al.·Clin Oral Investig
2020
INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH.
Hathazi D et al.·Brain
2021
SIL1 mutations and clinical spectrum in patients with Marinesco-Sjogren syndrome.
Krieger M et al.·Brain
2013Cohort
Genomics of chronic dry cough unravels neurological pathways.
Coley K et al.·Eur Respir J
2025
Ataxia and Hypogonadism: a Review of the Associated Genes and Syndromes.
De Michele G et al.·Cerebellum
2024Review
Exome sequencing revealed variants in SGCA and SIL1 genes underlying limb girdle muscular dystrophy and Marinesco-Sjögren syndrome patients.
Faheem A et al.·Mol Biol Rep
2024Cohort
A Novel SIL1 Variant (p.E342K) Associated with Marinesco-Sjögren Syndrome Impairs Protein Stability and Function.
Ruggieri AG et al.·Int J Mol Sci
2025Case report
A nationwide survey on Marinesco-Sjögren syndrome in Japan.
Goto M et al.·Orphanet J Rare Dis
2014
Phenotype-genotype correlations in patients with Marinesco-Sjögren syndrome.
Ezgu F et al.·Clin Genet
2014Cohort
Marinesco-Sjögren syndrome due to SIL1 mutations with a comment on the clinical phenotype.
Horvers M et al.·Eur J Paediatr Neurol
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools