FKTN

fukutin

Basic information

Region (hg38): 9:105558122-105653820

Previous symbols: [ "FCMD" ]

Links

ENSG00000106692 ∙ NCBI:2218 ∙ OMIM:607440 ∙ HGNC:3622 ∙ Uniprot:O75072 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2M (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (Strong), mode of inheritance: AR
• dilated cardiomyopathy 1X (Limited), mode of inheritance: AR
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (Supportive), 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 2M (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, 4 (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (Strong), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2M (Strong), mode of inheritance: AR
• myopathy caused by variation in FKTN (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1X; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4	AR	Cardiovascular; Musculoskeletal	Surveillance for cardiovascular complications may allow early diagnosis and treatment, which may ameliorate morbidity and mortality; Cardiomyopathy, dilated, 1X has been reported as being treated with transplant; Individuals with Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 has been reported as benefiting from treatment with steroids	Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	7258547; 8124873; 9690476; 10545611; 10817652; 12601708; 17036286; 17044012; 17878207; 18177472; 19015585; 19342235; 19299310; 19179078; 19842201; 20627570; 20961758

ClinVar

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

• Walker-Warburg congenital muscular dystrophy (36 variants)
• Dilated cardiomyopathy 1X (10 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (9 variants)
• not provided (8 variants)
• Cardiovascular phenotype (5 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2M (3 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4;Dilated cardiomyopathy 1X;Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;Autosomal recessive limb-girdle muscular dystrophy type 2M (2 variants)
• Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4 (1 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4;Autosomal recessive limb-girdle muscular dystrophy type 2M;Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4 (1 variants)
• Dilated cardiomyopathy 1X;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4;Autosomal recessive limb-girdle muscular dystrophy type 2M;Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (1 variants)
• FKTN-related disorder (1 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FKTN 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			1	166	1	168
missense	2	4	299	3		308
nonsense	20	22				42
start loss						0
frameshift	18	40	6			64
inframe indel			6			6
splice donor/acceptor (+/-2bp)	1	24	2	1		28
splice region			19	27		46
non coding		1	65	147	21	234
Total	41	91	379	317	22

Highest pathogenic variant AF is 0.000165

Variants in FKTN

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

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

Position	Type	Phenotype	Significance	ClinVar
9-105558147-C-T			Likely benign (Apr 09, 2018)
9-105558154-CT-C		not specified	Benign (May 08, 2015)
9-105558166-G-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	Uncertain significance (Aug 30, 2017)
9-105558166-G-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 • Dilated cardiomyopathy 1X • Dilated cardiomyopathy 1X;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4;Autosomal recessive limb-girdle muscular dystrophy type 2M;Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1	Uncertain significance (Jul 22, 2021)
9-105558205-T-A			Likely benign (Dec 03, 2020)
9-105573413-T-C			Likely benign (Dec 03, 2020)
9-105573427-C-T			Likely benign (Dec 03, 2020)
9-105573550-T-C			Benign (Dec 03, 2020)
9-105573553-G-A			Likely benign (Dec 03, 2020)
9-105573553-G-T			Likely benign (May 25, 2021)
9-105573554-G-C			Likely benign (May 25, 2021)
9-105573627-CA-C			Likely benign (Oct 30, 2019)
9-105573627-C-CA			Benign (May 24, 2021)
9-105573677-G-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 • Dilated cardiomyopathy 1X	Benign/Likely benign (Jun 23, 2018)
9-105573699-A-G		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 • Dilated cardiomyopathy 1X	Uncertain significance (Jan 12, 2018)
9-105573721-G-A		Dilated cardiomyopathy 1X • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	Uncertain significance (Jan 13, 2018)
9-105573727-A-T		not specified	Benign (Apr 07, 2014)
9-105573739-T-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 • Dilated cardiomyopathy 1X • not specified • FKTN-related disorder	Conflicting classifications of pathogenicity (Jan 13, 2018)
9-105573742-CA-C		not specified • Dilated Cardiomyopathy, Recessive • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	Conflicting classifications of pathogenicity (Feb 19, 2018)
9-105573754-A-G		Dilated cardiomyopathy 1X	Uncertain significance (Mar 24, 2023)
9-105573789-T-C			Benign (Jun 23, 2018)
9-105573866-G-A			Likely benign (May 26, 2021)
9-105573867-T-C			Benign (Jun 23, 2018)
9-105573989-A-G			Likely benign (Jun 25, 2020)
9-105574601-C-T			Likely benign (Aug 07, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FKTN	protein_coding	protein_coding	ENST00000223528	9	82989

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.66e-7	0.982	125569	0	179	125748	0.000712

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0466	239	237	1.01	0.0000123	3051
Missense in Polyphen		60	62.521	0.95968		808
Synonymous	1.24	72	86.7	0.830	0.00000461	836
Loss of Function	2.18	14	26.0	0.538	0.00000141	299

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00158	0.00158
Ashkenazi Jewish	0.00785	0.00787
East Asian	0.000381	0.000381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000381	0.000381
South Asian	0.000425	0.000425
Other	0.000656	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Glycosyltransferase 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). Required for normal location of POMGNT1 in Golgi membranes, and for normal POMGNT1 activity (PubMed:17034757). May interact with and reinforce a large complex encompassing the outside and inside of muscle membranes. Could be involved in brain development. {ECO:0000269|PubMed:17034757, ECO:0000269|PubMed:25279699}.
• Disease: DISEASE: Muscular dystrophy-dystroglycanopathy congenital without mental retardation B4 (MDDGB4) [MIM:613152]: An autosomal recessive disorder characterized by congenital muscular dystrophy and evidence of dystroglycanopathy. Features included increased serum creatine kinase, generalized weakness, mild white matter changes on brain MRI, and absence of mental retardation. {ECO:0000269|PubMed:14627679, ECO:0000269|PubMed:18177472, ECO:0000269|PubMed:19179078, ECO:0000269|PubMed:19299310}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C4 (MDDGC4) [MIM:611588]: An autosomal recessive degenerative myopathy characterized by progressive weakness of the pelvic and shoulder girdle muscles, and elevated serum creatine kinase. MDDGC4 has no brain involvement and a remarkable clinical response to corticosteroids. {ECO:0000269|PubMed:17044012, ECO:0000269|PubMed:19342235}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1X (CMD1X) [MIM:611615]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:17036286}. 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: 0.389

Intolerance Scores

• loftool: 0.322
• rvis_EVS: 0.58
• rvis_percentile_EVS: 82.25

Haploinsufficiency Scores

• pHI: 0.0950
• hipred: N
• hipred_score: 0.348
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.479

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fktn
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; 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); 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); homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; growth/size/body region phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: fktn
• Affected structure: ocular blood vessel
• Phenotype tag: abnormal
• Phenotype quality: deformed

Gene ontology

• Biological process: protein O-linked glycosylation;nervous system development;muscle organ development;negative regulation of cell population proliferation;protein O-linked mannosylation;negative regulation of JNK cascade;regulation of protein glycosylation
• Cellular component: extracellular space;nucleus;endoplasmic reticulum;Golgi apparatus;cis-Golgi network;integral component of Golgi membrane
• Molecular function: protein binding;transferase activity