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
• 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
• autosomal recessive limb-girdle muscular dystrophy type 2I (Definitive), 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 (60 variants)
• not provided (16 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 (14 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2I (10 variants)
• Cardiovascular phenotype (3 variants)
• Muscular dystrophy-dystroglycanopathy type B5;Autosomal recessive limb-girdle muscular dystrophy type 2I;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (2 variants)
• Muscular dystrophy-dystroglycanopathy type B5 (2 variants)
• Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 5 (1 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5;Muscular dystrophy-dystroglycanopathy type B5;Autosomal recessive limb-girdle muscular dystrophy type 2I (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy (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.

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			2	368	2	372
missense	9	34	386	2		431
nonsense	16	29	1			46
start loss	3					3
frameshift	42	32	4			78
inframe indel	1	2	9			12
splice donor/acceptor (+/-2bp)						0
splice region			1		1	2
non coding	1		11	19	4	35
Total	72	97	413	389	6

Highest pathogenic variant AF is 0.0000527

Variants in FKRP

This is a list of pathogenic ClinVar variants found in the FKRP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-46746070-TGGCGGC-T		not specified	Likely benign (Jul 21, 2017)
19-46746071-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2I	Pathogenic (Jan 11, 2017)
19-46746070-T-TGGCGGCGGC		not specified	Likely benign (Apr 24, 2017)
19-46746073-C-T		FKRP-related disorder	Likely benign (Oct 18, 2021)
19-46746094-A-G		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5	Uncertain significance (Nov 22, 2019)
19-46746095-G-A			Uncertain significance (Oct 27, 2023)
19-46746094-A-AGGCCG			Benign (Jun 07, 2018)
19-46746099-G-A		FKRP-related disorder	Likely benign (Apr 30, 2018)
19-46746104-G-A		not specified	Likely benign (Nov 02, 2016)
19-46746159-G-A		not specified	Uncertain significance (May 11, 2022)
19-46746180-G-A		not specified	Uncertain significance (May 25, 2022)
19-46746181-C-T		not specified	Uncertain significance (Apr 26, 2024)
19-46746249-T-G		not specified	Uncertain significance (Oct 19, 2021)
19-46746274-T-G		not specified	Uncertain significance (Oct 26, 2021)
19-46746318-G-T		not specified	Uncertain significance (Dec 22, 2023)
19-46746328-A-G		not specified	Uncertain significance (Feb 21, 2024)
19-46746375-G-T		not specified	Uncertain significance (Oct 03, 2022)
19-46746379-G-A		not specified	Uncertain significance (Jul 20, 2021)
19-46746401-G-T			Likely benign (Feb 26, 2018)
19-46746421-C-A			Uncertain significance (Nov 30, 2022)
19-46747902-G-A			Likely benign (Dec 01, 2021)
19-46748033-A-G			Likely benign (Apr 16, 2018)
19-46748073-G-T			Likely benign (Mar 14, 2018)
19-46748082-C-T		not specified	Likely benign (May 24, 2017)
19-46748084-A-G		not specified	Likely benign (Nov 30, 2016)

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
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: 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

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