ERLEC1

protein-coding

endoplasmic reticulum lectin 1, the group of MRH domain containing

Gene summary

This gene encodes a resident endoplasmic reticulum (ER) protein that functions in N-glycan recognition. This protein is thought to be involved in ER-associated degradation via its interaction with the membrane-associated ubiquitin ligase complex. It also functions as a regulator of multiple cellular stress-response pathways in a manner that promotes metastatic cell survival. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 21. [provided by RefSeq, Aug 2011]

Previous symbols:

C2orf30

MANE transcript

NM_015701.5

Inheritance

ClinVar variants

P:4U:86B:4

Top phenotype

autosomal dominant prognathism

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr2:53,787,009-53,833,038

External References & Databases

Ensembl (ENSG00000068912)

Transcript & Mutation Effects

hg38 • Region Span ~46.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant prognathismSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008312

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ERLEC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 72

Mandibular prognathiaTotal: 4

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015701.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense		4 clinvar	73 clinvar	3 clinvar		80
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			13 clinvar			13
Total	0	4	86	3	1	94

Highest pathogenic variant AF is 0.000053715565

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 84 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015701.5	RefSeq	NP_056516.2	14	MANE Select
ENST00000185150.9	Ensembl	ENSP00000185150.4	14	MANE Select
NM_001127397.3	RefSeq	NP_001120869.1	13	Standard
NM_001127398.3	RefSeq	NP_001120870.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
Disorders of transmembrane transporters
Disease
Signal Transduction
Defective CFTR causes cystic fibrosis

Biological Process

ubiquitin-dependent ERAD pathway
retrograde protein transport, ER to cytosol
ERAD pathway
transmembrane transport
negative regulation of retrograde protein transport, ER to cytosol

Molecular Function

protein binding
unfolded protein binding

Cellular Component

endoplasmic reticulum lumen
endoplasmic reticulum quality control compartment

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000185150
Coding exons: 14
Length: 31776
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125745
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.640	226	255	0.887	0.0000120	3148
Missense (PolyPhen)		55	80.659	0.68188		965
Synonymous	-0.562	100	93.1	1.07	0.00000468	885
Loss of Function	2.64	14	29.5	0.475	0.00000135	374

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00013	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00017	0.00015	rare
South Asian	0.000099	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable lectin that binds selectively to improperly folded lumenal proteins. May function in endoplasmic reticulum quality control and endoplasmic reticulum-associated degradation (ERAD) of both non-glycosylated proteins and glycoproteins. {ECO:0000269|PubMed:16531414, ECO:0000269|PubMed:18264092, ECO:0000269|PubMed:18502753}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.509
RVIS EVS: -0.69
RVIS percentile EVS: 15.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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