CRPPA
CDP-L-ribitol pyrophosphorylase A
Basic information
Region (hg38): 7:16087524-16502504
Previous symbols: [ "ISPD" ]
Links
Phenotypes
GenCC
Source:
- muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (Definitive), mode of inheritance: AR
- muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (Strong), mode of inheritance: AR
- muscular dystrophy-dystroglycanopathy, type A (Supportive), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2U (Supportive), mode of inheritance: AR
- congenital muscular dystrophy without intellectual disability (Supportive), mode of inheritance: AR
- muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (Strong), mode of inheritance: AR
- myopathy caused by variation in CRPPA (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Muscular dystrophy-dystroglycanopathy (congenital, with brain and eye anomalies), type A, 7; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 | AR | General | 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 | Musculoskeletal; Neurologic; Ophthalmologic | 7604843; 9492098; 22522421; 22522420; 23390185 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (222 variants)
- Congenital Muscular Dystrophy, alpha-dystroglycan related (213 variants)
- Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;Autosomal recessive limb-girdle muscular dystrophy type 2U (182 variants)
- Autosomal recessive limb-girdle muscular dystrophy type 2U;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (150 variants)
- not specified (36 variants)
- Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (13 variants)
- Inborn genetic diseases (10 variants)
- Autosomal recessive limb-girdle muscular dystrophy type 2U (9 variants)
- ISPD-Related Disorder (2 variants)
- Muscular dystrophy-dystroglycanopathy (2 variants)
- Congenital muscular dystrophy due to integrin alpha-7 deficiency (1 variants)
- CRPPA-related disorder (1 variants)
- Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRPPA gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 60 | 67 | ||||
| missense | 199 | 207 | ||||
| nonsense | 8 | |||||
| start loss | 3 | |||||
| frameshift | 11 | 16 | ||||
| inframe indel | 4 | |||||
| splice donor/acceptor (+/-2bp) | 9 | |||||
| splice region ? | 2 | 10 | 9 | 21 | ||
| non coding ? | 133 | 73 | 59 | 265 | ||
| Total | 22 | 11 | 346 | 138 | 62 |
Highest pathogenic variant AF is 0.0000329
Variants in CRPPA
This is a list of pathogenic ClinVar variants found in the CRPPA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-16087536-A-G | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 12, 2018) | ||
| 7-16087579-T-C | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16087603-T-C | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 12, 2018) | ||
| 7-16087626-G-A | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 12, 2018) | ||
| 7-16087672-G-A | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16087672-G-T | Congenital Muscular Dystrophy, alpha-dystroglycan related | Benign (Jan 13, 2018) | ||
| 7-16087685-C-T | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16087695-C-T | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 12, 2018) | ||
| 7-16087889-G-C | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16087903-T-C | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16088116-GA-G | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jun 14, 2016) | ||
| 7-16088134-T-C | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16088145-C-A | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 12, 2018) | ||
| 7-16088170-A-G | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16088204-C-T | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16088220-G-A | Congenital Muscular Dystrophy, alpha-dystroglycan related | Benign (Jan 12, 2018) | ||
| 7-16088238-C-G | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16088300-T-A | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 12, 2018) | ||
| 7-16088321-G-A | Congenital Muscular Dystrophy, alpha-dystroglycan related | Likely benign (Jan 12, 2018) | ||
| 7-16088333-G-A | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 12, 2018) | ||
| 7-16088408-C-T | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 12, 2018) | ||
| 7-16088411-T-C | Congenital Muscular Dystrophy, alpha-dystroglycan related | Likely benign (Jan 13, 2018) | ||
| 7-16088412-C-T | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jan 13, 2018) | ||
| 7-16088412-CTTTTTTTT-C | Congenital Muscular Dystrophy, alpha-dystroglycan related | Benign (Jun 14, 2016) | ||
| 7-16088412-C-CTT | Congenital Muscular Dystrophy, alpha-dystroglycan related | Uncertain significance (Jun 14, 2016) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CRPPA | protein_coding | protein_coding | ENST00000407010 | 10 | 330131 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000252 | 0.984 | 124609 | 0 | 28 | 124637 | 0.000112 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.413 | 167 | 183 | 0.914 | 0.00000875 | 2898 |
| Missense in Polyphen | 49 | 53.701 | 0.91246 | 739 | ||
| Synonymous | -1.78 | 84 | 65.6 | 1.28 | 0.00000332 | 867 |
| Loss of Function | 2.14 | 9 | 19.1 | 0.471 | 9.64e-7 | 278 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000351 | 0.000348 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000180 | 0.000167 |
| Finnish | 0.0000939 | 0.0000928 |
| European (Non-Finnish) | 0.000145 | 0.000133 |
| Middle Eastern | 0.000180 | 0.000167 |
| South Asian | 0.0000338 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Cytidylyltransferase required for protein O-linked mannosylation (PubMed:26687144, PubMed:27130732, PubMed:27601598, PubMed:22522420, PubMed:22522421). Catalyzes the formation of CDP- ribitol nucleotide sugar from D-ribitol 5-phosphate (PubMed:26687144, PubMed:27130732). CDP-ribitol is a substrate of FKTN during the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine- beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:26687144, PubMed:27130732). Shows activity toward other pentose phosphate sugars and mediates formation of CDP-ribulose or CDP-ribose using CTP and ribulose-5-phosphate or ribose-5- phosphate, respectively (PubMed:26687144). Not Involved in dolichol production (PubMed:26687144). {ECO:0000269|PubMed:22522420, ECO:0000269|PubMed:22522421, ECO:0000269|PubMed:26687144, ECO:0000269|PubMed:27130732, ECO:0000269|PubMed:27601598}.;
- Disease
- DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C7 (MDDGC7) [MIM:616052]: A form of muscular dystrophy resulting from defective glycosylation of alpha-dystroglycan, and characterized by a limb-girdle phenotype with muscular weakness apparent after ambulation is achieved. MDDGC7 individuals do not show epilepsy, mental retardation, structural eye/brain abnormalities, or white matter changes. {ECO:0000269|PubMed:23288328, ECO:0000269|PubMed:23390185, ECO:0000269|PubMed:27234031}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Mannose type O-glycan biosynthesis - Homo sapiens (human);Pentose and glucuronate interconversions - Homo sapiens (human)
(Consensus)
Haploinsufficiency Scores
- pHI
- hipred
- N
- hipred_score
- 0.198
- ghis
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ispd
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- ispd
- Affected structure
- muscle
- Phenotype tag
- abnormal
- Phenotype quality
- collapsed
Gene ontology
- Biological process
- axon guidance;isoprenoid biosynthetic process;protein O-linked mannosylation
- Cellular component
- cytosol
- Molecular function
- protein homodimerization activity;D-ribitol-5-phosphate cytidylyltransferase activity;cytidylyltransferase activity