Emery-Dreifuss muscular dystrophy: genes and variants

Genes linked to Emery-Dreifuss muscular dystrophy

• LMNA: Prelamin-A/C

  The gene product produces lamins A and C, structural proteins that form the nuclear lamina beneath the inner nuclear membrane. Lamins help maintain nuclear shape and organize chromatin, and LMNA variants are associated with muscular dystrophy, cardiomyopathy, lipodystrophy, and premature-aging syndromes.

  12 disease-causing and 71 uncertain variants in LMNA are linked to Emery-Dreifuss muscular dystrophy.

• TMEM43: Transmembrane protein 43

  A multi-pass membrane protein that helps organize protein complexes at the inner nuclear membrane and retain emerin. It also participates in innate-immune signaling and contributes to electrical coupling in the inner ear, with variants linked to cardiomyopathy and auditory neuropathy.

  0 disease-causing and 31 uncertain variants in TMEM43 are linked to Emery-Dreifuss muscular dystrophy.

• FHL1: Four and a half LIM domains protein 1

  It organizes protein complexes in striated muscle and participates in mechanosensing, sarcomere structure, and transcriptional responses. X-linked pathogenic variants cause a spectrum including reducing-body myopathy, Emery-Dreifuss muscular dystrophy, scapuloperoneal myopathy, and cardiomyopathy.

  0 disease-causing and 0 uncertain variants in FHL1 are linked to Emery-Dreifuss muscular dystrophy.

Weakly linked (only a few uncertain records): ESR1.

Where Emery-Dreifuss muscular dystrophy variants cluster

• LMNA LTD (positions 428–545): 4 of 12 disease-causing changes, 1.9× more than its size predicts.
• LMNA Coil 2 (positions 243–383): 4 of 12 disease-causing changes, 1.6× more than its size predicts.

Known disease-causing variants in Emery-Dreifuss muscular dystrophy

Which prediction tools work for Emery-Dreifuss muscular dystrophy

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 81 out of 100

Same protein, different disease

• Charcot-Marie-Tooth disease is also caused by LMNA variants; they fall mostly in different places as the Emery-Dreifuss muscular dystrophy variants (130 disease-causing).
• Dilated cardiomyopathy is also caused by LMNA variants; they fall mostly in different places as the Emery-Dreifuss muscular dystrophy variants (21 disease-causing).
• Familial partial lipodystrophy, Dunnigan type is also caused by LMNA variants; they fall partly in the same places as the Emery-Dreifuss muscular dystrophy variants (13 disease-causing).
• Congenital muscular dystrophy due to LMNA mutation is also caused by LMNA variants; they fall partly in the same places as the Emery-Dreifuss muscular dystrophy variants (11 disease-causing).
• Hutchinson-Gilford syndrome is also caused by LMNA variants; they fall partly in the same places as the Emery-Dreifuss muscular dystrophy variants (9 disease-causing).

Diseases related to Emery-Dreifuss muscular dystrophy

• Arrhythmogenic right ventricular dysplasia, also linked to LMNA and TMEM43
• Charcot-Marie-Tooth disease, also linked to LMNA
• Dilated cardiomyopathy, also linked to LMNA
• Bethlem myopathy, also linked to LMNA
• Primary dilated cardiomyopathy, also linked to LMNA
• X-linked myopathy with postural muscle atrophy, also linked to FHL1
• Auditory neuropathy, also linked to TMEM43
• Familial partial lipodystrophy, Dunnigan type, also linked to LMNA
• Congenital muscular dystrophy due to LMNA mutation, also linked to LMNA
• Muscular dystrophy, also linked to LMNA
• Primary familial dilated cardiomyopathy, also linked to LMNA
• Hutchinson-Gilford syndrome, also linked to LMNA

Frequently asked questions

Which genes are linked to Emery-Dreifuss muscular dystrophy?

In CATVariant, Emery-Dreifuss muscular dystrophy is linked to 3 analyzed proteins: LMNA (Prelamin-A/C), TMEM43 (Transmembrane protein 43) and FHL1 (Four and a half LIM domains protein 1).

How many genetic variants are linked to Emery-Dreifuss muscular dystrophy?

175 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 103 are of uncertain significance or have conflicting reports.

Which uncertain variants in Emery-Dreifuss muscular dystrophy look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Emery-Dreifuss muscular dystrophy?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.81, based on 10 disease-causing and 27 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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