SEL1L

SEL1L adaptor subunit of ERAD E3 ubiquitin ligase

Basic information

Region (hg38): 14:81471547-81533853

Links

ENSG00000071537

∙ NCBI:6400 ∙ OMIM:602329 ∙ HGNC:10717 ∙ Uniprot:Q9UBV2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinemia	AR	Allergy/Immunology/Infectious	The condition has been described as involving early-onset agammaglobulinemia and recurrent, severe infections, and awareness may allow preventative measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	37943610; 37943617

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEL1L gene.

not_specified (74 variants)
not_provided (4 variants)
Neurodevelopmental_disorder_with_hypotonia,_poor_growth,_dysmorphic_facies,_and_agammaglobulinemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEL1L gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005065.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense	1 clinvar		74 clinvar		1 clinvar	76
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	74	1	2

Highest pathogenic variant AF is 6.841583e-7

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEL1L	protein_coding	protein_coding	ENST00000336735	21	62313

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.982	0.0177	125730	0	17	125747	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.41	289	430	0.672	0.0000218	5191
Missense in Polyphen		84	167.27	0.50218		1968
Synonymous	0.156	153	155	0.984	0.00000794	1484
Loss of Function	5.32	8	47.6	0.168	0.00000228	584

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000280	0.000275
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000887	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000675	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays a role in the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:16186509). Enhances SYVN1 stability. Plays a role in LPL maturation and secretion. Required for normal differentiation of the pancreas epithelium, and for normal exocrine function and survival of pancreatic cells. May play a role in Notch signaling. {ECO:0000250|UniProtKB:Q9Z2G6, ECO:0000269|PubMed:16186509}.;
Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Disorders of transmembrane transporters;Disease;Signal Transduction;Defective CFTR causes cystic fibrosis;ER Quality Control Compartment (ERQC);Calnexin/calreticulin cycle;Post-translational protein modification;Metabolism of proteins;Transport of small molecules;Hedgehog ligand biogenesis;Signaling by Hedgehog;Asparagine N-linked glycosylation;ABC-family proteins mediated transport;N-glycan trimming in the ER and Calnexin/Calreticulin cycle;Hh mutants that don,t undergo autocatalytic processing are degraded by ERAD;Hh mutants abrogate ligand secretion;ABC transporter disorders;Diseases of signal transduction (Consensus)

Recessive Scores

pRec: 0.186

Intolerance Scores

loftool: 0.492
rvis_EVS: 0.15
rvis_percentile_EVS: 64.74

Haploinsufficiency Scores

pHI: 0.366
hipred: Y
hipred_score: 0.756
ghis: 0.430

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.952

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Sel1l
Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; 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); liver/biliary system phenotype; skeleton phenotype; digestive/alimentary phenotype;

Zebrafish Information Network

Gene name: sel1l
Affected structure: post-vent vasculature
Phenotype tag: abnormal
Phenotype quality: hemorrhagic

Gene ontology

Biological process: triglyceride metabolic process;Notch signaling pathway;protein secretion;ubiquitin-dependent ERAD pathway;retrograde protein transport, ER to cytosol;ERAD pathway;protein stabilization;transmembrane transport;endoplasmic reticulum mannose trimming
Cellular component: Hrd1p ubiquitin ligase complex;Hrd1p ubiquitin ligase ERAD-L complex;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;Derlin-1 retrotranslocation complex;endoplasmic reticulum quality control compartment
Molecular function: protein binding