FKTN

Summary

FKTN (fukutin, HGNC:3622) is a protein-coding gene on chromosome 9q31.2, encoding Ribitol-5-phosphate transferase FKTN (O75072). Catalyzes the transfer of a ribitol-phosphate from CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglyc….

The protein encoded by this gene is a putative transmembrane protein that is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of alpha-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development. Defects in this gene are a cause of Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X). Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 2218 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy caused by variation in FKTN (Definitive, ClinGen) — +8 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,177 total — 65 pathogenic, 89 likely-pathogenic
• Phenotypes (HPO): 174
• MANE Select transcript: NM_001079802

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3622
Approved symbol	FKTN
Name	fukutin
Location	9q31.2
Locus type	gene with protein product
Status	Approved
Aliases	LGMD2M
Ensembl gene	ENSG00000106692
Ensembl biotype	protein_coding
OMIM	607440
Entrez	2218

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 21 protein_coding, 16 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000223528, ENST00000357998, ENST00000374705, ENST00000448551, ENST00000457847, ENST00000479846, ENST00000490134, ENST00000602526, ENST00000602661, ENST00000642177, ENST00000642537, ENST00000642644, ENST00000642952, ENST00000644273, ENST00000645933, ENST00000674563, ENST00000674633, ENST00000674767, ENST00000675232, ENST00000675443, ENST00000675668, ENST00000675695, ENST00000675736, ENST00000676011, ENST00000676192, ENST00000676310, ENST00000676371, ENST00000906332, ENST00000906333, ENST00000906334, ENST00000906335, ENST00000906336, ENST00000906337, ENST00000922137, ENST00000922138, ENST00000922139, ENST00000922140, ENST00000922141, ENST00000922142, ENST00000967515

RefSeq mRNA: 10 — MANE Select: NM_001079802 NM_001079802, NM_001198963, NM_001351496, NM_001351497, NM_001351498, NM_001351499, NM_001351500, NM_001351501, NM_001351502, NM_006731

CCDS: CCDS6766

Canonical transcript exons

ENST00000357998 — 11 exons

Exon	Start	End
ENSE00001208473	105635051	105641118
ENSE00001756840	105573655	105573746
ENSE00003460668	105604215	105604492
ENSE00003507736	105617959	105618092
ENSE00003522212	105619934	105620061
ENSE00003549229	105596598	105596657
ENSE00003552714	105574945	105575137
ENSE00003553591	105607819	105607951
ENSE00003579860	105601145	105601348
ENSE00003619834	105615278	105615407
ENSE00003903964	105558131	105558165

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 88.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0832 / max 229.6578, expressed in 1641 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97845	7.0832	1641

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	88.11	gold quality
adrenal tissue	UBERON:0018303	86.49	gold quality
germinal epithelium of ovary	UBERON:0001304	85.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.34	gold quality
ventricular zone	UBERON:0003053	83.07	gold quality
skin of hip	UBERON:0001554	82.23	gold quality
CA1 field of hippocampus	UBERON:0003881	81.99	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.81	gold quality
stromal cell of endometrium	CL:0002255	81.54	gold quality
body of pancreas	UBERON:0001150	81.21	gold quality
corpus callosum	UBERON:0002336	80.89	gold quality
rectum	UBERON:0001052	80.28	gold quality
pancreas	UBERON:0001264	80.04	gold quality
ganglionic eminence	UBERON:0004023	80.02	gold quality
sural nerve	UBERON:0015488	79.70	gold quality
islet of Langerhans	UBERON:0000006	79.17	gold quality
colonic epithelium	UBERON:0000397	79.14	gold quality
right uterine tube	UBERON:0001302	78.92	gold quality
cortical plate	UBERON:0005343	78.87	gold quality
left ovary	UBERON:0002119	78.76	gold quality
right ovary	UBERON:0002118	78.75	gold quality
upper leg skin	UBERON:0004262	78.49	gold quality
endometrium	UBERON:0001295	78.34	gold quality
tibial nerve	UBERON:0001323	78.23	gold quality
tendon	UBERON:0000043	78.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.72	gold quality
mucosa of stomach	UBERON:0001199	77.57	gold quality
stomach	UBERON:0000945	77.47	gold quality
ovary	UBERON:0000992	77.34	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

236 targeting FKTN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 23)

• In Fukuyama congenital muscular dystrophy (FCMD) cases, expression of fukutin looked decreased. (PMID:12172906)
• Fukutin is associated with Walker-Warburg syndrome. (PMID:14627679)
• Data suggest that fukutin and fukutin-related protein (FKRP) may be involved at different steps in O-mannosylglycan synthesis of alpha-dystroglycan, and FKRP is most likely involved in the initial step in this synthesis. (PMID:15213246)
• Fukutin seems to bind to both the hypoglycosylated and fully glycosylated form of alpha-dystroglycan, and seems bind to the core area rather than the sugar chain of alpha-dystroglycan (PMID:17005282)
• Walker-Warburg syndrome carries a homozygous-single nucleotide insertion that produces a frameshift, or 2 mutations, a point mutation that produces an amino acid substitution, & deletion in 3’UTR that affects the polyadenylation signal of fukutin gene. (PMID:18177472)
• FCMD mutations are a more common cause of Walker-Warburg syndrome outside of the Middle East. (PMID:18752264)
• The homozygous nonsense mutations within the coding region identified in Turkish patients are predicted to cause a total loss of fukutin activity and are likely to produce a more severe phenotype which closely resembles WWS. (PMID:18834683)
• The compound heterozygous FKTN mutation was a rare cause of dilated cardiomyopathy. Hyper-CKemia might be indicative of FKTN mutation in dilated cardiomyopathy. (PMID:19015585)
• Outside Japan, fukutinopathies are associated with a large spectrum of phenotypes from isolated hyperCKaemia to severe CMD, showing a clear overlap with that of FKRP. (PMID:19179078)
• an identical homozygous c.1167insA mutation in the FKTN gene on a common haplotype in four families and identified 2/299 (0.7%) carriers for the c.1167insA mutation among normal American Ashkenazi Jewish adults (PMID:19266496)
• Our results provide further evidence for ethnic and allelic heterogeneity and the presence of milder phenotypes in FKTN-dystroglycanopathy despite a substantial degree of alpha-dystroglycan hypoglycosylation in skeletal muscle. (PMID:19342235)
• We found fukutin gene mutations in a 4.5-year-old Italian patient, with reduced alpha-dystroglycan expression, dystrophic features on muscle biopsy, hypotonia since birth, mild myopathy, but no brain involvement. (PMID:19396839)
• FKTN mutations are the most common genetic cause of congenital muscular dystrophies with defective alpha-dystroglycan glycosylation in Korea (PMID:20620061)
• four new non-Japanese patients with FKTN mutations and congenital muscular dystrophy (PMID:20961758)
• Mutation in the fukutin gene is associated with Fukuyama congenital muscular dystrophy and microcephaly. (PMID:24530477)
• Fukutin role in in tumor progression in gastric cancer (PMID:26223471)
• Fukutin and fukutin-related protein are sequentially acting Rbo5P transferases that use cytidine diphosphate ribitol. (PMID:26923585)
• ISPD and FKTN are essential for the incorporation of ribitol into alpha-dystroglycan. (PMID:27194101)
• the mutated fukutin protein was smaller than the normal protein, reflecting the truncation of fukutin due to a premature stop codon. Immunostaining analysis showed a decrease in the signal for the glycosylated form of alpha-dystroglycan. These findings indicated that this mutation is the second most prevalent loss-of-function mutation in Japanese Fukuyama congenital muscular dystrophy patients. (PMID:28680109)
• The results suggest that fukutin and FKRP not only participate in the synthesis of O-mannosyl glycans added to alpha-dystroglycan in the endoplasmic reticulum and Golgi complex, but that they could also play a role, that remains to be established, in the nucleus of retinal neurons. (PMID:29416295)
• Fukutin, FKRP, and TMEM5 form a complex while maintaining each of their enzyme activities. Data showed that endogenous fukutin and FKRP enzyme activities coexist with TMEM5 enzyme activity, and suggest the possibility that formation of this enzyme complex may contribute to specific and prompt biosynthesis of glycans that are required for dystroglycan function. (PMID:29477842)
• Fukutin Protein Participates in Cell Proliferation by Enhancing Cyclin D1 Expression through Binding to the Transcription Factor Activator Protein-1: An In Vitro Study. (PMID:34830034)
• Compound variants of FKTN, POMGNT1, and LAMB1 gene identified by prenatal whole-exome sequencing in three fetuses with congenital hydrocephalus. (PMID:35843586)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	fktn	ENSDARG00000059437
mus_musculus	Fktn	ENSMUSG00000028414
rattus_norvegicus	Fktn	ENSRNOG00000028129
caenorhabditis_elegans		WBGENE00011554
caenorhabditis_elegans		WBGENE00020307
caenorhabditis_elegans		WBGENE00020924
caenorhabditis_elegans		WBGENE00020927
caenorhabditis_elegans		WBGENE00021249

Protein

Protein identifiers

Ribitol-5-phosphate transferase FKTN — O75072 (reviewed: O75072)

Alternative names: Fukutin, Fukuyama-type congenital muscular dystrophy protein, Ribitol-5-phosphate transferase

All UniProt accessions (16): O75072, A0A2R8Y4L5, A0A2R8Y6X6, A0A2R8Y768, A0A2R8Y7E3, A0A2R8YDW9, A0A6Q8PEY6, A0A6Q8PF14, A0A6Q8PG65, A0A6Q8PG93, A0A6Q8PGS8, A0A6Q8PGV4, A0A6Q8PHN1, H7C3W5, I7HPB4, R4GMU0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a ribitol-phosphate from CDP-ribitol to the distal N-acetylgalactosamine 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). This constitutes the first step in the formation of the ribitol 5-phosphate tandem repeat which links the phosphorylated O-mannosyl trisaccharide to the ligand binding moiety composed of repeats of 3-xylosyl-alpha-1,3-glucuronic acid-beta-1. Required for normal location of POMGNT1 in Golgi membranes, and for normal POMGNT1 activity. May interact with and reinforce a large complex encompassing the outside and inside of muscle membranes. Could be involved in brain development.

Subunit / interactions. Forms a complex composed of FKTN/fukutin, FKRP and RXYLT1/TMEM5. Interacts (via transmembrane domain) with POMGNT1; the interaction is direct and is required for normal POMGNT1 location in Golgi membranes.

Subcellular location. Golgi apparatus membrane. Cytoplasm. Nucleus.

Tissue specificity. Expressed in the retina (at protein level). Widely expressed with highest expression in brain, heart, pancreas and skeletal muscle. Expressed at similar levels in control fetal and adult brain. Expressed in migrating neurons, including Cajar-Retzius cells and adult cortical neurons, as well as hippocampal pyramidal cells and cerebellar Purkinje cells. No expression observed in the glia limitans, the subpial astrocytes (which contribute to basement membrane formation) or other glial cells.

Disease relevance. Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A4 (MDDGA4) [MIM:253800] An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound intellectual disability, 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. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy-dystroglycanopathy congenital without impaired intellectual development 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 intellectual disability. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the LicD transferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75072-1	1	yes
O75072-2	2

RefSeq proteins (10): NP_001073270, NP_001185892, NP_001338425, NP_001338426, NP_001338427, NP_001338428, NP_001338429, NP_001338430, NP_001338431, NP_006722 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007074	LicD/FKTN/FKRP_NTP_transf	Domain
IPR009644	FKTN/MNN-like	Family
IPR045587	FKTN_N	Domain

Pfam: PF04991, PF19737

Catalyzed reactions (Rhea), 1 shown:

• 3-O-[beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + CDP-L-ribitol = 3-O-[Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + CMP + H(+) (RHEA:36551)

UniProt features (25 total): sequence variant 15, topological domain 2, mutagenesis site 2, chain 1, transmembrane region 1, sequence conflict 1, region of interest 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75072-F1	92.48	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 92

Mutagenesis-validated functional residues (2):

Position	Phenotype
133	decrease in ribitol-5-phosphate transferase activity.
317	decrease in ribitol-5-phosphate transferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9939291	Matriglycan biosynthesis on DAG1

MSigDB gene sets: 452 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, YAGI_AML_WITH_INV_16_TRANSLOCATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_CEREBELLAR_CORTEX_DEVELOPMENT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1

GO Biological Process (14): protein O-linked glycosylation (GO:0006493), nervous system development (GO:0007399), muscle organ development (GO:0007517), negative regulation of cell population proliferation (GO:0008285), cerebellar cortex development (GO:0021695), cerebral cortex development (GO:0021987), protein O-linked glycosylation via mannose (GO:0035269), negative regulation of JNK cascade (GO:0046329), basement membrane organization (GO:0071711), skeletal muscle fiber differentiation (GO:0098528), obsolete protein glycosylation (GO:0006486), brain development (GO:0007420), glycoprotein metabolic process (GO:0009100), obsolete regulation of protein glycosylation (GO:0060049)

GO Molecular Function (3): phosphotransferase activity, for other substituted phosphate groups (GO:0016780), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (8): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cis-Golgi network (GO:0005801), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DAG1 glycosylations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	4
animal organ development	2
anatomical structure development	2
Golgi apparatus	2
cytoplasm	2
endomembrane system	2
cellular anatomical structure	2
glycoprotein biosynthetic process	1
system development	1
muscle structure development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cerebellum development	1
pallium development	1
protein O-linked glycosylation	1
JNK cascade	1
negative regulation of MAPK cascade	1
regulation of JNK cascade	1
extracellular matrix organization	1
myotube differentiation	1
skeletal muscle cell differentiation	1
central nervous system development	1
head development	1
protein metabolic process	1
carbohydrate derivative metabolic process	1
transferase activity, transferring phosphorus-containing groups	1
binding	1
catalytic activity	1
bounding membrane of organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKTN	POMGNT1	Q8WZA1	990
FKTN	FKRP	Q9H9S5	988
FKTN	POMT2	Q9UKY4	986
FKTN	POMT1	Q9Y6A1	986
FKTN	DAG1	Q14118	977
FKTN	LARGE1	O95461	927
FKTN	RXYLT1	Q9Y2B1	862
FKTN	POMGNT2	Q8NAT1	860
FKTN	B3GALNT2	Q8NCR0	846
FKTN	POMK	Q9H5K3	846
FKTN	AGRN	O00468	830
FKTN	TCAP	O15273	816
FKTN	GMPPB	Q9Y5P6	795
FKTN	LAMA2	P24043	794
FKTN	CRPPA	A4D126	792

IntAct

23 interactions, top by confidence:

A	B	Type	Score
FKTN	RXYLT1	psi-mi:“MI:0915”(physical association)	0.710
RXYLT1	FKTN	psi-mi:“MI:0915”(physical association)	0.710
RXYLT1	FKTN	psi-mi:“MI:0914”(association)	0.710
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
POMGNT1	FKTN	psi-mi:“MI:0915”(physical association)	0.460
FKTN	POMGNT1	psi-mi:“MI:0915”(physical association)	0.460
FKTN	POMGNT1	psi-mi:“MI:0403”(colocalization)	0.460
POMGNT1	FKTN	psi-mi:“MI:0403”(colocalization)	0.460
FKRP	FKTN	psi-mi:“MI:0914”(association)	0.430
FKTN	FKRP	psi-mi:“MI:0914”(association)	0.430
FKRP	FKTN	psi-mi:“MI:0403”(colocalization)	0.430
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
RXYLT1	RTL8C	psi-mi:“MI:0914”(association)	0.350
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC39A14	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Proximity Label-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-MS), FKTN (Affinity Capture-RNA)

ESM2 similar proteins: A2XFP3, A2ZI32, A4VCL2, B4JW99, B4LCX4, B8AIZ4, F4J2C8, O22775, O75063, O75072, P14599, P45895, P54360, P86275, Q0KHV6, Q10MQ0, Q2QXP0, Q2TBE6, Q5K027, Q5MJS3, Q5RH51, Q5SP46, Q5XIL2, Q5ZEQ8, Q5ZIK0, Q6DCQ8, Q6GX83, Q6H765, Q6PE18, Q701R1, Q701R2, Q86BJ3, Q8CBQ5, Q8CID3, Q8IXL6, Q8R507, Q8RXE1, Q8T5G8, Q8VCS3, Q93ZX7

Diamond homologs: O75072, Q10044, Q60HG0, Q68W49, Q8R507, P14184, Q1RGU4, Q4UND5, Q8CG64, Q9H9S5, Q9ZCN4, Q9ZCN5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FKTN	“form complex”	“Fukutin-FKRP-TMEM5 multienzyme complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

1177 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	65
Likely pathogenic	89
Uncertain significance	470
Likely benign	368
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012340	NM_001079802.2(FKTN):c.165+1427A>G	Pathogenic
1063728	NM_001079802.2(FKTN):c.1198_1207del (p.Cys400fs)	Pathogenic
1070267	NC_000009.11:g.(?108337304)(108397555_?)del	Pathogenic
1070650	NM_001079802.2(FKTN):c.914G>A (p.Trp305Ter)	Pathogenic
1072787	NM_001079802.2(FKTN):c.585dup (p.Asp196Ter)	Pathogenic
1073035	NM_001079802.2(FKTN):c.93T>A (p.Tyr31Ter)	Pathogenic
1076223	NC_000009.11:g.(?108320401)(108337428_?)del	Pathogenic
1252030	NM_001079802.2(FKTN):c.78C>G (p.Tyr26Ter)	Pathogenic
1350606	NM_001079802.2(FKTN):c.420_432dup (p.Pro145Ter)	Pathogenic
1363376	NM_001079802.2(FKTN):c.180dup (p.Phe61fs)	Pathogenic
1451446	NM_001079802.2(FKTN):c.942T>G (p.Tyr314Ter)	Pathogenic
1456977	NM_001079802.2(FKTN):c.395del (p.Asn132fs)	Pathogenic
1459095	NC_000009.11:g.(?108337314)(108468054_?)del	Pathogenic
1760944	NM_001079802.2(FKTN):c.786C>A (p.Tyr262Ter)	Pathogenic
193830	NM_001079802.1(FKTN):c.*4375_*4376ins3062	Pathogenic
1979862	NM_001079802.2(FKTN):c.626_627dup (p.Tyr210fs)	Pathogenic
2018600	NM_001079802.2(FKTN):c.630T>A (p.Tyr210Ter)	Pathogenic
2127577	NM_001079802.2(FKTN):c.473dup (p.Leu160fs)	Pathogenic
2186733	NC_000009.12:g.105604215del	Pathogenic
235328	NM_001079802.2(FKTN):c.369+1G>T	Pathogenic
2423628	NC_000009.11:g.(?108335926)(108403409_?)del	Pathogenic
2423629	NC_000009.11:g.(?108358859)(108484922_?)del	Pathogenic
2423630	NC_000009.11:g.(?108377549)(108382383_?)del	Pathogenic
2709569	NM_001079802.2(FKTN):c.107dup (p.Asn36fs)	Pathogenic
2720195	NM_001079802.2(FKTN):c.745G>T (p.Glu249Ter)	Pathogenic
2761205	NM_001079802.2(FKTN):c.844C>T (p.Gln282Ter)	Pathogenic
2779477	NM_001079802.2(FKTN):c.803_804del (p.Val268fs)	Pathogenic
2787966	NM_001079802.2(FKTN):c.979_985dup (p.Ser329fs)	Pathogenic
2812185	NM_001079802.2(FKTN):c.479del (p.Leu160fs)	Pathogenic
2851153	NM_001079802.2(FKTN):c.165G>A (p.Trp55Ter)	Pathogenic

SpliceAI

2582 predictions. Top by Δscore:

Variant	Effect	Δscore
9:105570654:G:GT	donor_gain	1.0000
9:105570654:G:T	donor_gain	1.0000
9:105575134:AAAGG:A	donor_loss	1.0000
9:105575138:G:C	donor_loss	1.0000
9:105575139:T:A	donor_loss	1.0000
9:105596592:TCCTA:T	acceptor_loss	1.0000
9:105596593:CCTAG:C	acceptor_loss	1.0000
9:105596596:A:AC	acceptor_loss	1.0000
9:105596596:A:AG	acceptor_gain	1.0000
9:105596596:AGAAT:A	acceptor_gain	1.0000
9:105596597:G:GG	acceptor_gain	1.0000
9:105596597:GA:G	acceptor_gain	1.0000
9:105596597:GAAT:G	acceptor_gain	1.0000
9:105596597:GAATG:G	acceptor_gain	1.0000
9:105596654:G:GG	donor_gain	1.0000
9:105601143:A:AG	acceptor_gain	1.0000
9:105601144:G:GG	acceptor_gain	1.0000
9:105601144:GC:G	acceptor_gain	1.0000
9:105601144:GCGT:G	acceptor_gain	1.0000
9:105601346:GAG:G	donor_gain	1.0000
9:105601349:G:C	donor_loss	1.0000
9:105601350:T:A	donor_loss	1.0000
9:105604207:G:A	acceptor_gain	1.0000
9:105604489:ACAGG:A	donor_loss	1.0000
9:105604491:AGGT:A	donor_loss	1.0000
9:105604493:G:C	donor_loss	1.0000
9:105604493:G:GG	donor_gain	1.0000
9:105604494:T:A	donor_loss	1.0000
9:105607814:TTCA:T	acceptor_loss	1.0000
9:105607815:TCA:T	acceptor_loss	1.0000

AlphaMissense

2854 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:105615389:A:C	S298R	0.998
9:105615391:C:A	S298R	0.998
9:105615391:C:G	S298R	0.998
9:105618088:G:A	G347E	0.998
9:105619951:A:C	E354D	0.998
9:105619951:A:T	E354D	0.998
9:105619991:T:C	F368L	0.998
9:105619993:T:A	F368L	0.998
9:105619993:T:G	F368L	0.998
9:105615392:A:C	S299R	0.997
9:105615394:T:A	S299R	0.997
9:105615394:T:G	S299R	0.997
9:105617961:T:A	W305R	0.997
9:105617961:T:C	W305R	0.997
9:105619943:A:C	S352R	0.997
9:105619945:C:A	S352R	0.997
9:105619945:C:G	S352R	0.997
9:105619953:T:C	L355P	0.997
9:105617968:G:C	R307P	0.996
9:105618087:G:T	G347W	0.996
9:105618088:G:T	G347V	0.996
9:105635052:T:C	Y392H	0.996
9:105615383:T:A	W296R	0.995
9:105615383:T:C	W296R	0.995
9:105619983:T:C	L365P	0.995
9:105620021:T:A	W378R	0.995
9:105620021:T:C	W378R	0.995
9:105575081:A:C	S17R	0.994
9:105575083:T:A	S17R	0.994
9:105575083:T:G	S17R	0.994

dbSNP variants (sampled 300 via entrez): RS1000002250 (9:105590647 G>A), RS1000035790 (9:105569856 A>G), RS1000137334 (9:105558512 C>G), RS1000175240 (9:105573675 A>G), RS1000195862 (9:105610263 C>G), RS1000234334 (9:105636641 C>T), RS1000243947 (9:105629108 C>T), RS1000244431 (9:105636303 A>G), RS1000285197 (9:105615181 G>C,T), RS1000334530 (9:105603479 A>C), RS1000413313 (9:105561808 A>G), RS1000418386 (9:105636402 C>A,G,T), RS1000431764 (9:105617039 G>C), RS1000480043 (9:105573929 G>A), RS1000568700 (9:105638333 G>A)

Disease associations

OMIM: gene MIM:607440 | disease phenotypes: MIM:236670, MIM:611615, MIM:253800, MIM:611588, MIM:613152, MIM:115200

GenCC curated gene-disease

Disease	Classification	Inheritance
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	Definitive	Autosomal recessive
autosomal recessive limb-girdle muscular dystrophy type 2M	Definitive	Autosomal recessive
muscular dystrophy-dystroglycanopathy	Strong	Autosomal recessive
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
congenital muscular dystrophy without intellectual disability	Supportive	Autosomal recessive
muscle-eye-brain disease	Supportive	Autosomal recessive
muscular dystrophy-dystroglycanopathy, type A	Supportive	Autosomal recessive
dilated cardiomyopathy 1X	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
myopathy caused by variation in FKTN	Definitive	AR

Mondo (16): muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171), dilated cardiomyopathy 1X (MONDO:0012704), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (MONDO:0009678), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (MONDO:0009364), autosomal recessive limb-girdle muscular dystrophy type 2M (MONDO:0012699), muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4 (MONDO:0013156), dilated cardiomyopathy (MONDO:0005021), myopathy caused by variation in FKTN (MONDO:0700067), cardiomyopathy (MONDO:0004994), hypertrophic cardiomyopathy (MONDO:0005045), familial dilated cardiomyopathy (MONDO:0016333), ventricular tachycardia (MONDO:0005477), muscular dystrophy-dystroglycanopathy (MONDO:0018276), (MONDO:0015470), (MONDO:0018279)

Orphanet (10): Walker-Warburg syndrome (Orphanet:899), Familial isolated dilated cardiomyopathy (Orphanet:154), Congenital muscular dystrophy, Fukuyama type (Orphanet:272), Muscle-eye-brain disease (Orphanet:588), Fukutin-related limb-girdle muscular dystrophy R13 (Orphanet:206554), Dilated cardiomyopathy (Orphanet:217604), Rare cardiomyopathy (Orphanet:167848), Rare hypertrophic cardiomyopathy (Orphanet:217569), Familial dilated cardiomyopathy (Orphanet:217607), Congenital muscular dystrophy due to dystroglycanopathy (Orphanet:370953)

HPO phenotypes

174 total (30 of 174 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000050	Hypoplastic male external genitalia
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000204	Cleft upper lip
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000298	Mask-like facies
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000413	Atresia of the external auditory canal
HP:0000482	Microcornea
HP:0000485	Megalocornea
HP:0000486	Strabismus
HP:0000496	Abnormality of eye movement
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000540	Hypermetropia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000404_1	Menarche (age at onset)	2.000000e-09
GCST001524_14	Visceral adipose tissue/subcutaneous adipose tissue ratio	4.000000e-06
GCST011494_49	Daytime nap	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0007828	daytime rest measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D058494	Walker-Warburg Syndrome	C10.500.507.450.499.249.500; C11.270.881; C16.131.666.507.450.499.249.500; C16.320.577.750
C566907	Cardiomyopathy, Dilated, 1x (supp.)
C566912	Muscular Dystrophy, Limb-Girdle, Type 2M (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	2
Particulate Matter	decreases expression, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
Vehicle Emissions	affects expression, increases abundance	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Folic Acid	decreases expression	1
Formaldehyde	decreases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_CV43	GM16192	Finite cell line	Male
CVCL_SN67	HAP1 FKTN (-) 1	Cancer cell line	Male
CVCL_SN68	HAP1 FKTN (-) 2	Cancer cell line	Male
CVCL_SN69	HAP1 FKTN (-) 3	Cancer cell line	Male
CVCL_SN70	HAP1 FKTN (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

297 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy