LYNX1

protein-coding

Ly6/neurotoxin 1, the group of LY6/PLAUR domain containing

Gene summary

This gene encodes a GPI-anchored, cell membrane bound member of the Ly6/uPAR (LU) superfamily of proteins containing the unique three-finger LU domain. This protein interacts with nicotinic acetylcholine receptors (nAChRs), and is thought to function as a modulator of nAChR activity to prevent excessive excitation. Alternatively spliced transcript variants have been found for this gene. Read-through transcription between this gene and the neighboring downstream gene (SLURP2) generates naturally-occurring transcripts (LYNX1-SLURP2) that encode a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Sep 2017]

MANE transcript

NM_177477.4

Inheritance

—

ClinVar variants

U:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr8:142,771,197-142,777,810

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~6.6 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 LYNX1 variants in ClinVar

1 Conditions Cataloged
not specifiedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_177477.4. 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.

EffectPLPVUSLBBSum
synonymous
0
missense
11
clinvar
11
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
Total00120012
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_177477.4RefSeqNP_803430.13MANE Select
ENST00000652477.1EnsemblENSP00000498325.13MANE Select
NM_001356370.1RefSeqNP_001343299.13Standard
NM_177457.5RefSeqNP_803252.13Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • synaptic transmission, cholinergic
  • regulation of neurotransmitter receptor activity
  • negative regulation of signaling receptor activity

Molecular Function

  • ion channel inhibitor activity
  • acetylcholine receptor regulator activity
  • acetylcholine receptor inhibitor activity
  • acetylcholine receptor binding

Cellular Component

  • endoplasmic reticulum
  • plasma membrane
  • membrane
  • dendrite
  • anchored component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000335822
Coding exons
4
Length
13889
Individuals with no LoFs
125435
Homozygous LoFs
0
Heterozygous LoFs
9
Defined
125444
p
0.0000359
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.9735781.80.6970.00000467831
Missense (PolyPhen)1322.4680.57859228
Synonymous0.05293535.40.9890.00000245253
Loss of Function1.0335.640.5323.32e-757

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.000100.000099rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000690.000062rare
South Asian00.0absent
Other0.000190.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Acts in different tissues through interaction to nicotinic acetylcholine receptors (nAChRs) (PubMed:21252236). The proposed role as modulator of nAChR activity seems to be dependent on the nAChR subtype and stoichiometry, and to involve an effect on nAChR trafficking and its cell surface expression, and on single channel properties of the nAChR inserted in the plasma membrane. Modulates functional properties of nicotinic acetylcholine receptors (nAChRs) to prevent excessive excitation, and hence neurodegeneration. Enhances desensitization by increasing both the rate and extent of desensitization of alpha- 4:beta-2-containing nAChRs and slowing recovery from desensitization. Promotes large amplitude ACh-evoked currents through alpha-4:beta-2 nAChRs. Is involved in regulation of the nAChR pentameric assembly in the endoplasmic reticulum. Shifts stoichiometry from high sensitivity alpha-4(2):beta-2(3) to low sensitivity alpha-4(3):beta-2(2) nAChR (By similarity). In vitro modulates alpha-3:beta-4-containing nAChRs. Reduces cell surface expression of (alpha-3:beta-4)(2):beta-4 and (alpha-3:beta- 4)(2):alpha-5 nAChRs suggesting an interaction with nAChR alpha- 3(-):(+)beta-4 subunit interfaces and an allosteric mode. Corresponding single channel effects characterized by decreased unitary conductance, altered burst proportions and enhanced desensitization/inactivation seem to depend on nAChR alpha:alpha subunit interfaces and are greater in (alpha-3:beta-2)(2):alpha-3 when compared to (alpha-3:beta-2)(2):alpha-5 nAChRs (PubMed:28100642). Prevents plasticity in the primary visual cortex late in life (By similarity). {ECO:0000250|UniProtKB:P0DP60, ECO:0000269|PubMed:21252236, ECO:0000269|PubMed:28100642}.;

Recessive Scores

pRec
0.127

Intolerance Scores

LoFtool
0.667
RVIS EVS
-0.27
RVIS percentile EVS
34.6

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.421

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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