FKTN

Chr 9AR

fukutin

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

NCBI Gene: 2218ENSG00000106692UniProt: O75072

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]

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1XMIM #611615
AR
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4MIM #253800
AR
Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 4MIM #613152
AR
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4MIM #611588
AR
587
ClinVar variants
108
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— FKTN
🧬
Gene-Disease Validity (ClinGen)
myopathy caused by variation in FKTN · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
108 Pathogenic / Likely Pathogenic· 260 VUS of 587 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.84LOEUF
pLI 0.000
Z-score 2.18
OE 0.54 (0.35–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.05Z-score
OE missense 1.01 (0.91–1.12)
239 obs / 237.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.35–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.91–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 14 / 26.0Missense obs/exp: 239 / 237.0Syn Z: 1.24

ClinVar Variant Classifications

587 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic65
VUS260
Likely Benign179
Benign11
Conflicting29
43
Pathogenic
65
Likely Pathogenic
260
VUS
179
Likely Benign
11
Benign
29
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
30
0
43
Likely Pathogenic
41
5
18
1
65
VUS
9
200
46
5
260
Likely Benign
1
6
85
87
179
Benign
0
0
11
0
11
Conflicting
—29
Total6421119093587

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

View in ClinVar →

Protein Context — Lollipop Plot

FKTN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

FKTN-related muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies, type A

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

FKTN-related muscular dystrophy-dystroglycanopathy limb-girdle

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
FUKUTIN; FKTN
MIM #607440 · *

Cardiomyopathy, dilated, 1X

MIM #611615

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4

MIM #253800

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 4

MIM #613152

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4

MIM #611588

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — FKTN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic variations and clinical spectrum of dystroglycanopathy in a large cohort of Chinese patients.
Song D et al.·Clin Genet
2021Cohort
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Pleiotropic effects of MORC2 derive from its epigenetic signature.
Peymani F et al.·Brain
2026
[Analysis of clinical features and FKTN gene variant in a child with congenital muscular dystrophy].
Zhang Y et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2022
Fukuyama congenital muscular dystrophy: Clinical features and therapeutic advances.
Ishigaki K et al.·Brain Dev
2025Review
Genetic and Clinical Spectrum of Limb-Girdle Muscular Dystrophies in Western Sicily.
Rini N et al.·Genes (Basel)
2025
Compound Heterozygous FKTN Variants in a Patient with Dilated Cardiomyopathy Led to an Aberrant α-Dystroglycan Pattern.
Gaertner A et al.·Int J Mol Sci
2022Case report
Molecular autopsy in maternal-fetal medicine.
Shamseldin HE et al.·Genet Med
2018
Compound variants of FKTN, POMGNT1, and LAMB1 gene identified by prenatal whole-exome sequencing in three fetuses with congenital hydrocephalus.
Li M et al.·J Obstet Gynaecol Res
2022Case report
The spectrum of hereditary neuromuscular disorders in the Pakistani population.
Akbar F et al.·Am J Med Genet A
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Limb Girdle Muscular DystrophyLimb-Girdle Muscular Dystrophy Type 2LGMD2I

A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)

RECRUITING
NCT05230459Phase PHASE1, PHASE2AskBio IncStarted 2023-05-15
AB-1003 dose level 1AB-1003 dose level 2Placebo
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools