SEL1L

Chr 14

SEL1L adaptor subunit of SYVN1 ubiquitin ligase

Also known as: Hrd3, NEDGSAF, NEDHGFA, PRO1063, SEL1-LIKE, SEL1L1

NCBI Gene: 6400 ENSG00000071537 UniProt: Q9UBV2

The SEL1L protein is essential for endoplasmic reticulum-associated degradation (ERAD), facilitating the removal and degradation of misfolded proteins from the ER and supporting pancreatic cell survival and exocrine function. Mutations cause autosomal recessive congenital disorder of glycosylation with severe developmental delays, seizures, and pancreatic dysfunction. This gene is highly constrained against loss-of-function variation, indicating its critical importance for normal cellular function.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is part of a protein complex required for the retrotranslocation or dislocation of misfolded proteins from the endoplasmic reticulum lumen to the cytosol, where they are degraded by the proteasome in a ubiquitin-dependent manner. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ResearchGenerating clinical summary…

LOEUF 0.30

Clinical Summary— SEL1L

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 84 VUS of 111 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.982

Z-score 5.32

OE 0.17 (0.10–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.41Z-score

OE missense 0.67 (0.61–0.74)

289 obs / 429.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.10–0.30)

0≤0.351.4

Missense OE?0.67 (0.61–0.74)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 8 / 47.6Missense obs/exp: 289 / 429.9Syn Z: 0.16

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS84

Likely Benign1

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	2
Likely Pathogenic	0	0	0	0
VUS	83	0	1	84
Likely Benign	0	0	1	1
Benign	1	1	1	3
Total	85	2	3	90

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap SEL1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →