CRPPA

Chr 7AR

CDP-L-ribitol pyrophosphorylase A

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

NCBI Gene: 729920ENSG00000214960UniProt: A4D126

This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

Primary Disease Associations & Inheritance

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7MIM #614643
AR
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7MIM #616052
AR
832
ClinVar variants
80
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CRPPA
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
80 Pathogenic / Likely Pathogenic· 208 VUS of 832 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.82LOEUF
pLI 0.000
Z-score 2.14
OE 0.47 (0.28–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.41Z-score
OE missense 0.91 (0.81–1.04)
167 obs / 182.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.28–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.81–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.28
0≤1.21.6
LoF obs/exp: 9 / 19.1Missense obs/exp: 167 / 182.7Syn Z: -1.78

ClinVar Variant Classifications

832 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic15
VUS208
Likely Benign117
Benign16
Conflicting7
65
Pathogenic
15
Likely Pathogenic
208
VUS
117
Likely Benign
16
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
4
47
0
65
Likely Pathogenic
7
2
5
1
15
VUS
1
123
82
2
208
Likely Benign
0
2
57
58
117
Benign
0
3
12
1
16
Conflicting
—7
Total2213420362428

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.

Gene2Phenotype Curations

CRPPA-related Walker-Warburg syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

MIM #614643

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7

MIM #616052

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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
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
The role of ratio markers based on prealbumin in the diagnosis of periprosthetic joint infection.
Cao Q et al.·Front Cell Infect Microbiol
2025
Brain pathology of lissencephaly type 2 with an ISPD pathogenic variant.
Keith J et al.·Neuropathol Appl Neurobiol
2023
Predictive values of body mass index, prognostic nutritional index and C-reactive protein to prealbumin ratio for prognosis of patients receiving radical gastrectomy.
Yang Y et al.·Nutr Hosp
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools