SLURP1

secreted LY6/PLAUR domain containing 1, the group of LY6/PLAUR domain containing

Basic information

Region (hg38): 8:142740948-142742406

Links

ENSG00000126233 ∙ NCBI:57152 ∙ OMIM:606119 ∙ HGNC:18746 ∙ Uniprot:P55000 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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
• mal de Meleda (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the SLURP1 gene.

• Acroerythrokeratoderma (20 variants)
• not provided (7 variants)
• Inborn genetic diseases (5 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	1	1	3
missense	2	1	9			12
nonsense	1	1				2
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			4	1		5
Total	4	3	14	2	1

Highest pathogenic variant AF is 0.0000788

Variants in SLURP1

This is a list of pathogenic ClinVar variants found in the SLURP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-142740997-C-T		Acroerythrokeratoderma	Uncertain significance (Jan 12, 2018)
8-142741000-C-T		Acroerythrokeratoderma	Likely benign (Jan 12, 2018)
8-142741129-C-T		Acroerythrokeratoderma	Uncertain significance (Jan 13, 2018)
8-142741133-C-T		Acroerythrokeratoderma	Uncertain significance (Jan 13, 2018)
8-142741145-A-G		Acroerythrokeratoderma	Conflicting classifications of pathogenicity (Sep 19, 2023)
8-142741156-T-C		not specified	Uncertain significance (Apr 25, 2023)
8-142741159-C-T		Acroerythrokeratoderma	Pathogenic (Mar 01, 2004)
8-142741169-G-A		Acroerythrokeratoderma	Pathogenic (Feb 14, 2023)
8-142741194-G-A		Acroerythrokeratoderma	Benign (Jan 23, 2024)
8-142741199-C-G		Acroerythrokeratoderma	Pathogenic (Jan 01, 2003)
8-142741199-C-T		Acroerythrokeratoderma	Pathogenic (Sep 01, 2022)
8-142741209-GGGGTCG-CT			Likely pathogenic (Mar 06, 2023)
8-142741212-G-T		Acroerythrokeratoderma	Pathogenic (-)
8-142741226-A-G		Acroerythrokeratoderma	Pathogenic (Mar 01, 2004)
8-142741244-G-A		Acroerythrokeratoderma	Pathogenic (-)
8-142741253-C-T		Acroerythrokeratoderma	Uncertain significance (Jan 12, 2018)
8-142741257-G-A			Likely benign (Jul 11, 2022)
8-142741279-G-A		Acroerythrokeratoderma	Uncertain significance (Jan 12, 2018)
8-142741284-G-A		SLURP1-related disorder	Likely benign (Sep 17, 2019)
8-142741802-C-T		Acroerythrokeratoderma	Pathogenic (Apr 01, 2001)
8-142741803-C-T			Likely pathogenic (Feb 01, 2017)
8-142741814-G-A		Acroerythrokeratoderma	Uncertain significance (Apr 28, 2017)
8-142741823-G-A		Acroerythrokeratoderma • not specified	Uncertain significance (Mar 01, 2024)
8-142741840-G-A		Acroerythrokeratoderma	Uncertain significance (Jan 13, 2018)
8-142741840-G-C		not specified	Uncertain significance (Jun 06, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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