LNX1

protein-coding

ligand of numb-protein X 1, the group of PDZ domain containing|Ring finger proteins

Gene summary

This gene encodes a membrane-bound protein that is involved in signal transduction and protein interactions. The encoded product is an E3 ubiquitin-protein ligase, which mediates ubiquitination and subsequent proteasomal degradation of proteins containing phosphotyrosine binding (PTB) domains. This protein may play an important role in tumorogenesis. Alternatively spliced transcript variants encoding distinct isoforms have been described. A pseudogene, which is located on chromosome 17, has been identified for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_001126328.3

Inheritance

—

ClinVar variants

U:111B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr4:53,459,301-53,701,405

External References & Databases

Ensembl (ENSG00000072201)

Transcript & Mutation Effects

hg38 • Region Span ~242.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LNX1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001126328.3. 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 clinvar		2
missense			109 clinvar	4 clinvar		113
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	111	5	0	116

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001126328.3	RefSeq	NP_001119800.1	10	MANE Select
ENST00000263925.8	Ensembl	ENSP00000263925.7	10	MANE Select
NM_032622.3	RefSeq	NP_116011.2	10	Standard
ENST00000306888.6	Ensembl	ENSP00000302879.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation
Notch signaling pathway

Biological Process

ubiquitin-dependent protein catabolic process
protein ubiquitination
protein homooligomerization

Molecular Function

ubiquitin-protein transferase activity
protein binding
PDZ domain binding
metal ion binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263925
Coding exons: 10
Length: 242105
Individuals with no LoFs: 125636
Homozygous LoFs: 0
Heterozygous LoFs: 112
Defined: 125748
p: 0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0553	432	429	1.01	0.0000241	4761
Missense (PolyPhen)		143	161.7	0.88433		1893
Synonymous	0.623	159	169	0.939	0.00000998	1460
Loss of Function	2.86	15	32.6	0.460	0.00000198	348

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00059	0.00055	rare
Latino/Admixed American	0.0011	0.0011	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00039	0.00038	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00038	0.00038	rare
South Asian	0.00023	0.00023	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NUMB. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of isoform p66 and isoform p72 of NUMB, but not that of isoform p71 or isoform p65. {ECO:0000250|UniProtKB:O70263}.;

Recessive Scores

pRec: 0.158

Intolerance Scores

LoFtool: 0.827
RVIS EVS: -1.19
RVIS percentile EVS: 5.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.840

Gene Damage Prediction

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