FKTN

Chr 9AR

fukutin

Also known as: CMD1X, FCMD, LGMD2M, LGMDR13, MDDGA4, MDDGB4, MDDGC4

NCBI Gene: 2218 ENSG00000106692 UniProt: O75072 OMIM: 607440

The encoded protein is a Golgi-localized glycosyltransferase that glycosylates alpha-dystroglycan, which is essential for proper muscle and brain function. Autosomal recessive mutations cause a spectrum of dystroglycanopathies ranging from severe congenital muscular dystrophy with brain and eye anomalies (including Fukuyama-type congenital muscular dystrophy and Walker-Warburg syndrome) to milder limb-girdle muscular dystrophy and dilated cardiomyopathy. The pathogenic mechanism involves defective glycosylation of alpha-dystroglycan, leading to impaired muscle membrane stability and abnormal neuronal migration during brain development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Nov 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.844 OMIM phenotypes

Clinical Summary— FKTN

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Gene-Disease Validity (ClinGen)

myopathy caused by variation in FKTN · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

188 unique Pathogenic / Likely Pathogenic· 467 VUS of 1174 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — FKTN

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.18

OE 0.54 (0.35–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.05Z-score

OE missense 1.01 (0.91–1.12)

239 obs / 237.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.54 (0.35–0.84)

0≤0.351.4

Missense OE?1.01 (0.91–1.12)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 14 / 26.0Missense obs/exp: 239 / 237.0Syn Z: 1.24

ClinVar Variant Classifications

1174 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic65

Likely Pathogenic123

VUS467

Likely Benign385

Benign28

Conflicting93

Pathogenic

123

Likely Pathogenic

467

VUS

385

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	46	1	18	0	65
Likely Pathogenic	108	10	4	1	123
VUS	14	361	85	7	467
Likely Benign	2	13	192	178	385
Benign	0	0	27	1	28
Conflicting	—				93
Total	170	385	326	187	1,161

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

38 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap FKTN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →