GeneBe

CRPPA

CDP-L-ribitol pyrophosphorylase A

Basic information

Region (hg38): 7:16087525-16502504

Previous symbols: [ "ISPD" ]

Links

ENSG00000214960 ∙ NCBI:729920 ∙ OMIM:614631 ∙ HGNC:37276 ∙ Uniprot:A4D126 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Muscular dystrophy-dystroglycanopathy (congenital, with brain and eye anomalies), type A, 7; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal; Neurologic; Ophthalmologic7604843; 9492098; 22522421; 22522420; 23390185

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRPPA gene.

  • Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A,_7 (391 variants)
  • Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2U (380 variants)
  • not_provided (205 variants)
  • not_specified (94 variants)
  • Congenital_Muscular_Dystrophy,_alpha-dystroglycan_related (32 variants)
  • CRPPA-related_disorder (10 variants)
  • ISPD-related_disorder (2 variants)
  • Muscular_dystrophy-dystroglycanopathy (2 variants)
  • Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_a,_8 (1 variants)
  • Congenital_muscular_dystrophy_due_to_integrin_alpha-7_deficiency (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. These statistics are base on transcript: NM_001101426.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
5
clinvar
102
clinvar
2
clinvar
 110
missense
6
clinvar
5
clinvar
231
clinvar
15
clinvar
1
clinvar
 258
nonsense
10
clinvar
1
clinvar
 11
start loss
1
2
1
 4
frameshift
15
clinvar
5
clinvar
1
clinvar
 21
splice donor/acceptor (+/-2bp)
5
clinvar
6
clinvar
2
clinvar
 13
Total 37 20 240 117 3

Highest pathogenic variant AF is 0.00011413078

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CRPPAprotein_codingprotein_codingENST00000407010 10330131
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.0002520.9841246090281246370.000112
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.4131671830.9140.000008752898
Missense in Polyphen4953.7010.91246739
Synonymous-1.788465.61.280.00000332867
Loss of Function2.14919.10.4719.64e-7278

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003510.000348
Ashkenazi Jewish0.000.00
East Asian0.0001800.000167
Finnish0.00009390.0000928
European (Non-Finnish)0.0001450.000133
Middle Eastern0.0001800.000167
South Asian0.00003380.0000327
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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