PPP1R13L

Chr 19AR

protein phosphatase 1 regulatory subunit 13 like

Also known as: ARCME, CMAEA, IASPP, NKIP1, RAI, RAI4

NCBI Gene: 10848 ENSG00000104881 UniProt: Q8WUF5 OMIM: 607463

The protein regulates apoptosis and transcription through interactions with NF-kappa-B and p53, and negatively regulates inflammatory responses. Biallelic mutations cause autosomal recessive arrhythmogenic cardiomyopathy with variable ectodermal abnormalities, affecting both cardiac and skin/hair/nail development. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.489).

OMIM ResearchSummary from OMIM, UniProt

IASPP is one of the most evolutionarily conserved inhibitors of p53 (TP53; MIM 191170), whereas ASPP1 (MIM 606455) and ASPP2 (MIM 602143) are activators of p53.[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.491 OMIM phenotype

Clinical Summary— PPP1R13L

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Gene-Disease Validity (ClinGen)

arrhythmogenic cardiomyopathy with variable ectodermal abnormalities · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

13 unique Pathogenic / Likely Pathogenic· 142 VUS of 217 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.032

Z-score 3.78

OE 0.28 (0.17–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.54Z-score

OE missense 0.80 (0.74–0.87)

392 obs / 487.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.17–0.49)

0≤0.351.4

Missense OE?0.80 (0.74–0.87)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 9 / 32.1Missense obs/exp: 392 / 487.4Syn Z: 0.99

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePPP1R13L-related dilated cardiomyopathyLOFAR

This gene — mechanism propensity

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

0.6452th %ile

GOF

0.6443th %ile

LOF

0.4528th %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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

217 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic9

VUS142

Likely Benign33

Benign11

Conflicting6

Pathogenic

Likely Pathogenic

142

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	0	0	0	4
Likely Pathogenic	8	1	0	0	9
VUS	2	137	3	0	142
Likely Benign	0	5	5	23	33
Benign	0	0	8	3	11
Conflicting	—				6
Total	14	143	16	26	205

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap PPP1R13L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →