FKRP

fukutin related protein

Basic information

Region (hg38): 19:46746046-46776988

Links

ENSG00000181027 ∙ NCBI:79147 ∙ OMIM:606596 ∙ HGNC:17997 ∙ Uniprot:Q9H9S5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the FKRP gene.

• Walker-Warburg_congenital_muscular_dystrophy (901 variants)
• Cardiovascular_phenotype (404 variants)
• Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2I (301 variants)
• not_provided (256 variants)
• Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A5 (172 variants)
• Muscular_dystrophy-dystroglycanopathy_type_B5 (116 variants)
• not_specified (107 variants)
• Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_A1 (68 variants)
• Autosomal_recessive_limb-girdle_muscular_dystrophy (22 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)
• Acute_rhabdomyolysis (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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	1	4	427	5	438
missense	13	82	458	12	3	568
nonsense	20	32	2			54
start loss	3	1				4
frameshift	50	45	5			100
splice donor/acceptor (+/-2bp)						0
Total	87	161	469	439	8

Highest pathogenic variant AF is 0.001972366

GnomAD

Source: gnomAD

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
		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: dbNSFP

• 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

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

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