SIL1

Chr 5AR

SIL1 nucleotide exchange factor

Also known as: BAP, MSS, ULG5

The protein functions as a nucleotide exchange factor for the ER luminal chaperone HSPA5 and is required for protein translocation and folding in the endoplasmic reticulum. Mutations cause Marinesco-Sjögren syndrome, inherited in an autosomal recessive pattern. The pathogenic mechanism appears to be dominant negative.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.641 OMIM phenotype
Clinical SummarySIL1
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Gene-Disease Validity (ClinGen)
Marinesco-Sjogren syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — SIL1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.012
Z-score 2.79
OE 0.34 (0.190.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.47Z-score
OE missense 0.92 (0.821.02)
234 obs / 255.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.190.64)
00.351.4
Missense OE0.92 (0.821.02)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 7 / 20.7Missense obs/exp: 234 / 255.2Syn Z: -0.64
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSIL1-related Marinesco-Sjoegren syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.6540th %ile
LOF
0.2385th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SIL1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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