SLURP1
secreted LY6/PLAUR domain containing 1, the group of LY6/PLAUR domain containing
Basic information
Region (hg38): 8:142740949-142742406
Links
Phenotypes
GenCC
Source:
- hereditary palmoplantar keratoderma, Gamborg-Nielsen type (Supportive), mode of inheritance: AR
- mal de Meleda (Supportive), mode of inheritance: AR
- mal de Meleda (Strong), mode of inheritance: AR
- palmoplantar keratosis (Limited), mode of inheritance: AD
- mal de Meleda (Strong), mode of inheritance: AR
- mal de Meleda (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Mal de Meleda | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Dermatologic | 4281438; 9887370; 11285253; 14756676; 20854438; 21690549; 23290002 |
| Heterozygotes may display milder manifestations |
ClinVar
This is a list of variants' phenotypes submitted to
- Acroerythrokeratoderma (24 variants)
- not_provided (13 variants)
- not_specified (9 variants)
- SLURP1-related_disorder (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLURP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020427.3. 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 | 4 | |||||
| missense | 14 | 23 | ||||
| nonsense | 2 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 10 | 6 | 15 | 2 | 1 |
Highest pathogenic variant AF is 0.0000663421
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SLURP1 | protein_coding | protein_coding | ENST00000246515 | 3 | 1468 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.259 | 0.648 | 124778 | 0 | 9 | 124787 | 0.0000361 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.591 | 52 | 65.5 | 0.794 | 0.00000415 | 667 |
| Missense in Polyphen | 13 | 19.449 | 0.66842 | 208 | ||
| Synonymous | -0.378 | 30 | 27.5 | 1.09 | 0.00000185 | 202 |
| Loss of Function | 1.24 | 1 | 3.51 | 0.285 | 1.52e-7 | 39 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000620 | 0.0000620 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000533 | 0.0000532 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000354 | 0.0000327 |
| Other | 0.000164 | 0.000164 |
dbNSFP
Source:
- Function
- FUNCTION: Has an antitumor activity (PubMed:8742060). Was found to be a marker of late differentiation of the skin. Implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin (PubMed:14721776, PubMed:17008884). In vitro down-regulates keratinocyte proliferation; the function may involve the proposed role as modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro inhibits alpha-7-dependent nAChR currents in an allosteric manner (PubMed:14506129, PubMed:26905431). In T cells may be involved in regulation of intracellular Ca(2+) signaling (PubMed:17286989). Seems to have a immunomodulatory function in the cornea (By similarity). The function may implicate a possible role as a scavenger receptor for PLAU thereby blocking PLAU- dependent functions of PLAUR such as in cell migration and proliferation (PubMed:25168896). {ECO:0000250|UniProtKB:Q9Z0K7, ECO:0000269|PubMed:14506129, ECO:0000269|PubMed:17286989, ECO:0000269|PubMed:26905431, ECO:0000269|PubMed:8742060, ECO:0000305|PubMed:14721776, ECO:0000305|PubMed:17008884}.;
- Disease
- DISEASE: Mal de Meleda (MDM) [MIM:248300]: A rare autosomal recessive skin disorder, characterized by diffuse transgressive palmoplantar keratoderma with keratotic lesions extending onto the dorsa of the hands and the feet (transgrediens). Patients may have hyperhidrosis. Other features include perioral erythema, lichenoid plaques on the knees and the elbows, and nail abnormalities. {ECO:0000269|PubMed:11285253, ECO:0000269|PubMed:12483299, ECO:0000269|PubMed:12950349, ECO:0000269|PubMed:14756676, ECO:0000269|PubMed:17008884, ECO:0000269|PubMed:19120323, ECO:0000269|PubMed:21690549, ECO:0000269|PubMed:24604124, ECO:0000269|PubMed:25919322}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.541
Intolerance Scores
- loftool
- 0.293
- rvis_EVS
- 0.17
- rvis_percentile_EVS
- 65.33
Haploinsufficiency Scores
- pHI
- 0.0793
- hipred
- N
- hipred_score
- 0.146
- ghis
- 0.480
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.415
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Low | Medium |
Mouse Genome Informatics
- Gene name
- Slurp1
- Phenotype
- limbs/digits/tail phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);
Gene ontology
- Biological process
- cell activation;cell adhesion;locomotory behavior;negative regulation of cell population proliferation;negative regulation of keratinocyte proliferation;negative regulation of cell migration;urokinase plasminogen activator signaling pathway;neuromuscular process controlling posture;positive regulation of signaling receptor activity
- Cellular component
- extracellular region;extracellular space;extracellular exosome
- Molecular function
- cytokine activity;protein binding;acetylcholine receptor activator activity