SLURP1

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the Ly6/uPAR family but lacks a GPI-anchoring signal sequence. It is thought that this secreted protein contains antitumor activity. Mutations in this gene have been associated with Mal de Meleda, a rare autosomal recessive skin disorder. This gene maps to the same chromosomal region as several members of the Ly6/uPAR family of glycoprotein receptors. [provided by RefSeq, Jul 2008]

MANE transcript

NM_020427.3

Inheritance

AD, AR

ClinVar variants

P:16U:15B:6

Top phenotype

Mal de Meleda

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr8:142,740,949-142,742,406

External References & Databases

Ensembl (ENSG00000126233)

Transcript & Mutation Effects

hg38 • Region Span ~1.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

palmoplantar keratosisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0006590

Submitter: Ambry Genetics

mal de MeledaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009552

Submitter: Ambry Genetics

mal de MeledaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009552

Submitter: PanelApp Australia

mal de MeledaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009552

Submitter: Orphanet

mal de MeledaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009552

Submitter: Genomics England PanelApp

mal de MeledaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009552

Submitter: Labcorp Genetics (formerly Invitae)

mal de MeledaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0009552

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Mal de MeledaAD/AR

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Comments: Heterozygotes may display milder manifestations

Refs: 4281438; 9887370; 11285253; 14756676; 20854438; 21690549; 23290002

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLURP1 variants in ClinVar

4 Conditions Cataloged

AcroerythrokeratodermaTotal: 23

not providedTotal: 19

not specifiedTotal: 11

SLURP1-related disorderTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020427.3. 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	4 clinvar	1 clinvar	6
missense	5 clinvar	3 clinvar	14 clinvar	1 clinvar		23
nonsense	1 clinvar	1 clinvar				2
start loss		1 clinvar				1
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
Total	9	7	15	5	1	37

Highest pathogenic variant AF is 0.00006634211

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020427.3	RefSeq	NP_065160.1	3	MANE Select
ENST00000246515.2	Ensembl	ENSP00000246515.1	3	MANE Select
ENST00001102773.1	Ensembl	ENSP00000772578.1	3	Standard
ENST00001134969.1	Ensembl	ENSP00000802407.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell activation
cell adhesion
locomotory behavior
negative regulation of cell population proliferation
negative regulation of keratinocyte proliferation

Molecular Function

cytokine activity
protein binding
acetylcholine receptor activator activity

Cellular Component

extracellular region
extracellular space
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000246515
Coding exons: 3
Length: 1468
Individuals with no LoFs: 124778
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 124787
p: 0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.591	52	65.5	0.794	0.00000415	667
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000035	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.415

Gene Damage Prediction

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