LYNX1
protein-codingLy6/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
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.6 kbGenCC 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
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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 11 | 11 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 12 | 0 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_803430.1 | 3 | MANE Select | |
| Ensembl | ENSP00000498325.1 | 3 | MANE Select | |
| RefSeq | NP_001343299.1 | 3 | Standard | |
| RefSeq | NP_803252.1 | 3 | Standard |
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:
- 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-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.973 | 57 | 81.8 | 0.697 | 0.00000467 | 831 |
| Missense (PolyPhen) | 13 | 22.468 | 0.57859 | 228 | ||
| Synonymous | 0.0529 | 35 | 35.4 | 0.989 | 0.00000245 | 253 |
| Loss of Function | 1.03 | 3 | 5.64 | 0.532 | 3.32e-7 | 57 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000069 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00019 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |