CRPPA

Chr 7AR

CDP-L-ribitol pyrophosphorylase A

Also known as: ISPD, LGMDR20, MDDGA7, MDDGC7, Nip, hISPD

NCBI Gene: 729920ENSG00000214960UniProt: A4D126OMIM: 614631

This gene encodes a cytidylyltransferase that catalyzes the formation of CDP-ribitol, which is essential for protein O-linked mannosylation and proper functioning of alpha-dystroglycan in binding extracellular matrix proteins. Mutations cause muscular dystrophy-dystroglycanopathy with either severe congenital presentation including brain and eye anomalies (Walker-Warburg syndrome) or milder limb-girdle muscular dystrophy. The condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.822 OMIM phenotypes
Clinical Summary— CRPPA
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Gene-Disease Validity (ClinGen)
myopathy caused by variation in CRPPA · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 107 VUS of 200 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
0.82LOEUF
pLI 0.000
Z-score 2.14
OE 0.47 (0.28–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.41Z-score
OE missense 0.91 (0.81–1.04)
167 obs / 182.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.28–0.82)
0≤0.351.4
Missense OE0.91 (0.81–1.04)
0≤0.61.4
Synonymous OE1.28
0≤1.21.6
LoF obs/exp: 9 / 19.1Missense obs/exp: 167 / 182.7Syn Z: -1.78

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic5
VUS107
Likely Benign61
Conflicting2
21
Pathogenic
5
Likely Pathogenic
107
VUS
61
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
12
0
21
Likely Pathogenic
2
0
3
0
5
VUS
1
94
11
1
107
Likely Benign
0
0
29
32
61
Benign
0
0
0
0
0
Conflicting
—2
Total12945533196

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

View in ClinVar →

Protein Context — Lollipop Plot

CRPPA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Cytidine Diphosphate-Ribitol Analysis for Diagnostics and Treatment Monitoring of Cytidine Diphosphate-l-Ribitol Pyrophosphorylase A Muscular Dystrophy.
van Tol W et al.·Clin Chem
2019Case report
Whole-genome sequencing unravels novel genetic determinants and regulatory pathways associated with triamcinolone acetonide-induced ocular hypertension.
Badrinarayanan L et al.·Mol Genet Genomics
2023
Analysis of genotype-phenotype correlation in Walker-Warburg syndrome with a novel CRPPA mutation in different clinical manifestations.
Bayram N et al.·Eur J Ophthalmol
2022Case report
Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period.
Sframeli M et al.·Neuromuscul Disord
2017Cohort
Neuroimaging manifestations and genetic heterogeneity of Walker-Warburg syndrome in Saudi patients.
Alharbi S et al.·Brain Dev
2021Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients