SLURP1

Chr 8AR

secreted LY6/PLAUR domain containing 1

Also known as: ANUP, ARS, ArsB, LY6-MT, LY6LS, MDM

NCBI Gene: 57152 ENSG00000126233 UniProt: P55000 OMIM: 606119

This protein maintains the physiological and structural integrity of keratinocyte layers in the skin and modulates nicotinic acetylcholine receptor activity to regulate keratinocyte proliferation and differentiation. Mutations cause Meleda disease, a rare autosomal recessive skin disorder characterized by palmoplantar keratoderma. The gene shows relatively low constraint against loss-of-function variants (pLI 0.26, LOEUF 1.31), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.311 OMIM phenotype

Clinical Summary— SLURP1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

18 unique Pathogenic / Likely Pathogenic· 21 VUS of 51 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.259

Z-score 1.24

OE 0.28 (0.10–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.59Z-score

OE missense 0.79 (0.64–1.00)

52 obs / 65.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.10–1.31)

0≤0.351.4

Missense OE?0.79 (0.64–1.00)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 1 / 3.5Missense obs/exp: 52 / 65.5Syn Z: -0.38

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLURP1-related palmoplantar keratoderma transgrediens (Mal de Meleda)LOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6356th %ile

GOF

0.6444th %ile

LOF

0.2386th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13

Likely Pathogenic5

VUS21

Likely Benign6

Benign3

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	6	3	0	13
Likely Pathogenic	3	2	0	0	5
VUS	0	15	5	1	21
Likely Benign	0	0	3	3	6
Benign	0	0	2	1	3
Conflicting	—				2
Total	7	23	13	5	50

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

58 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap SLURP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →