FKRP
fukutin related protein
Basic information
Region (hg38): 19:46746046-46776988
Links
Phenotypes
GenCC
Source:
- muscular dystrophy-dystroglycanopathy type B5 (Definitive), mode of inheritance: AR
- muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 (Definitive), mode of inheritance: AR
- muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 (Strong), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2I (Strong), mode of inheritance: AR
- muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 (Moderate), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2I (Definitive), mode of inheritance: AR
- muscular dystrophy-dystroglycanopathy, type A (Supportive), mode of inheritance: AR
- muscle-eye-brain disease (Supportive), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2I (Supportive), mode of inheritance: AR
- congenital muscular dystrophy with cerebellar involvement (Supportive), mode of inheritance: AR
- congenital muscular dystrophy with intellectual disability (Supportive), mode of inheritance: AR
- congenital muscular dystrophy without intellectual disability (Supportive), mode of inheritance: AR
- muscular dystrophy-dystroglycanopathy type B5 (Strong), mode of inheritance: AR
- autosomal recessive limb-girdle muscular dystrophy type 2I (Strong), mode of inheritance: AR
- myopathy caused by variation in FKRP (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, 5; Muscular dystrophy-dystroglycanopathy (congenital with or without impaired intellectual development), type B, 5; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 | AR | Cardiovascular | Individuals have been described with cardiovascular complications (eg, left-ventricular dysfunction), and recognition may allow surveillance (eg, with echocardiogram) and early medical management aimed at optimizing cardiac function; Cardiac transplantation has been described | Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic | 9577386; 10838249; 11592034; 11320179; 11741828; 12707425; 14647208; 15121789; 14523375; 15580560; 16634037; 16476814; 17336067; 18060779; 18639457; 18671187; 19705481; 19917824; 20301582; 20627570 |
ClinVar
This is a list of variants' phenotypes submitted to
- Walker-Warburg_congenital_muscular_dystrophy (887 variants)
- Cardiovascular_phenotype (391 variants)
- Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2I (301 variants)
- not_provided (247 variants)
- Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A5 (171 variants)
- Muscular_dystrophy-dystroglycanopathy_type_B5 (114 variants)
- not_specified (101 variants)
- Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A1 (68 variants)
- Autosomal_recessive_limb-girdle_muscular_dystrophy (20 variants)
- FKRP-related_disorder (20 variants)
- Myopathy_caused_by_variation_in_FKRP (5 variants)
- Muscular_dystrophy-dystroglycanopathy_(congenital_without_impaired_intellectual_development),_type_B,_5 (4 variants)
- Abnormality_of_the_musculature (3 variants)
- Cardiomyopathy (2 variants)
- Primary_dilated_cardiomyopathy (2 variants)
- Muscular_dystrophy-dystroglycanopathy (2 variants)
- Hypertrophic_cardiomyopathy (2 variants)
- Limb-girdle_muscular_dystrophy (2 variants)
- Headache (1 variants)
- Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A,_4 (1 variants)
- Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_a,_10 (1 variants)
- Difficulty_standing (1 variants)
- Paresthesia (1 variants)
- Intellectual_disability (1 variants)
- Nizon-Isidor_syndrome (1 variants)
- Difficulty_climbing_stairs (1 variants)
- FKRP-related_muscular_dystrophy-dystroglycanopathy (1 variants)
- Muscle_weakness (1 variants)
- Hereditary_skeletal_muscle_disorder (1 variants)
- Scapular_winging (1 variants)
- Difficulty_walking (1 variants)
- Neuronopathy,_distal_hereditary_motor,_type_2B (1 variants)
- Muscular_dystrophy (1 variants)
- Gait_imbalance (1 variants)
- Myopathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FKRP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024301.5. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 423 | 433 | ||||
| missense | 11 | 77 | 454 | 13 | 558 | |
| nonsense | 19 | 32 | 53 | |||
| start loss | 3 | 1 | 4 | |||
| frameshift | 49 | 43 | 97 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 83 | 154 | 465 | 436 | 7 |
Highest pathogenic variant AF is 0.001972366
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FKRP | protein_coding | protein_coding | ENST00000318584 | 1 | 30943 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00000984 | 0.571 | 125057 | 0 | 17 | 125074 | 0.0000680 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.85 | 230 | 324 | 0.711 | 0.0000263 | 3002 |
| Missense in Polyphen | 85 | 124.52 | 0.68262 | 1243 | ||
| Synonymous | 2.05 | 126 | 159 | 0.793 | 0.0000136 | 1137 |
| Loss of Function | 0.780 | 9 | 11.9 | 0.756 | 5.88e-7 | 118 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000110 | 0.000109 |
| Finnish | 0.000288 | 0.000234 |
| European (Non-Finnish) | 0.0000761 | 0.0000708 |
| Middle Eastern | 0.000110 | 0.000109 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000353 | 0.000328 |
dbNSFP
Source:
- Function
- FUNCTION: Transferase involved in 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. {ECO:0000269|PubMed:25279699}.;
- Disease
- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A5 (MDDGA5) [MIM:613153]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:15121789}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy-dystroglycanopathy congenital with or without mental retardation B5 (MDDGB5) [MIM:606612]: A congenital muscular dystrophy characterized by a severe phenotype with inability to walk, muscle hypertrophy, marked elevation of serum creatine kinase, secondary deficiency of laminin alpha2, and a marked reduction in alpha-dystroglycan expression. Only a subset of affected individuals have brain involvements. {ECO:0000269|PubMed:11592034, ECO:0000269|PubMed:12654965, ECO:0000269|PubMed:12666124, ECO:0000269|PubMed:14652796, ECO:0000269|PubMed:17336067}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C5 (MDDGC5) [MIM:607155]: An autosomal recessive degenerative myopathy with age of onset ranging from childhood to adult life, and variable severity. Clinical features include proximal muscle weakness, waddling gait, calf hypertrophy, cardiomyopathy and respiratory insufficiency. A reduction of alpha-dystroglycan and laminin alpha-2 expression can be observed on skeletal muscle biopsy from MDDGC5 patients. {ECO:0000269|PubMed:11741828, ECO:0000269|PubMed:12666124, ECO:0000269|PubMed:14523375, ECO:0000269|PubMed:14647208, ECO:0000269|PubMed:23800702}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Mannose type O-glycan biosynthesis - Homo sapiens (human)
(Consensus)
Recessive Scores
- pRec
- 0.287
Haploinsufficiency Scores
- pHI
- 0.164
- hipred
- N
- hipred_score
- 0.417
- ghis
- 0.431
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.189
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fkrp
- Phenotype
- growth/size/body region phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system 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); normal 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); vision/eye phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- fkrp
- Affected structure
- muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- irregular spatial pattern
Gene ontology
- Biological process
- protein processing;protein O-linked mannosylation
- Cellular component
- Golgi membrane;extracellular space;nucleus;rough endoplasmic reticulum;Golgi apparatus;cytosol;integral component of membrane;sarcolemma
- Molecular function
- dystroglycan binding;transferase activity