Mutilating keratoderma: genes and variants
Mutilating keratoderma is linked to 1 analyzed protein (GJB2). 15 DNA variants are known to cause it; 11 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Mutilating keratoderma
GJB2: Gap junction beta-2 protein
Its connexin 26 channels support potassium and metabolite recycling within the cochlea and communication across epithelial gap junctions. Biallelic pathogenic variants are among the most common causes of congenital nonsyndromic hearing loss, while dominant variants can cause syndromic deafness with skin disease.
15 disease-causing and 11 uncertain variants in GJB2 are linked to Mutilating keratoderma.
Where Mutilating keratoderma variants cluster
- GJB2 Transmembrane (positions 74–94): 4 of 15 disease-causing changes, 2.9× more than its size predicts.
- GJB2 Transmembrane (positions 136–156): 3 of 15 disease-causing changes, 2.1× more than its size predicts.
Known disease-causing variants in Mutilating keratoderma
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| GJB2 R143W | 143 | Transmembrane | Disease-causing (★★★★) |
| GJB2 R143Q | 143 | Transmembrane | Disease-causing (★★) |
| GJB2 R32S | 32 | Transmembrane | Disease-causing (★★) |
| GJB2 V84L | 84 | Transmembrane | Disease-causing (★★) |
| GJB2 T86R | 86 | Transmembrane | Disease-causing (★★) |
| GJB2 M93I | 93 | Transmembrane | Disease-causing (★★) |
| GJB2 C169Y | 169 | Extracellular | Disease-causing (★★) |
| GJB2 G12V | 12 | Intramembrane | Disease-causing (★★) |
| GJB2 G45E | 45 | Extracellular | Disease-causing (★★) |
| GJB2 W77R | 77 | Transmembrane | Disease-causing (★★) |
| GJB2 V95M | 95 | Cytoplasmic | Disease-causing (★★) |
| GJB2 W172R | 172 | Extracellular | Disease-causing (★★) |
| GJB2 K15T | 15 | Cytoplasmic | Disease-causing (★★) |
| GJB2 S139N | 139 | Transmembrane | Disease-causing (★★) |
| GJB2 D66H | 66 | Extracellular | Disease-causing |
Which prediction tools work for Mutilating keratoderma
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)
- REVEL: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 93 out of 100
- CADD: 87 out of 100
- phyloP: 77 out of 100
Same protein, different disease
- Autosomal recessive nonsyndromic hearing loss 4 is also caused by GJB2 variants; they fall partly in the same places as the Mutilating keratoderma variants (38 disease-causing).
- Nonsyndromic genetic hearing loss is also caused by GJB2 variants; they fall partly in the same places as the Mutilating keratoderma variants (28 disease-causing).
- Rare genetic deafness is also caused by GJB2 variants; they fall partly in the same places as the Mutilating keratoderma variants (25 disease-causing).
- Ichthyosis, hystrix-like, with hearing loss is also caused by GJB2 variants; they fall mostly in different places as the Mutilating keratoderma variants (13 disease-causing).
- Autosomal dominant keratitis-ichthyosis-hearing loss syndrome is also caused by GJB2 variants; they fall partly in the same places as the Mutilating keratoderma variants (13 disease-causing).
Diseases related to Mutilating keratoderma
- Autosomal recessive nonsyndromic hearing loss 4, also linked to GJB2
- Noonan syndrome, also linked to GJB2
- Rare genetic deafness, also linked to GJB2
- Autosomal dominant nonsyndromic hearing loss, also linked to GJB2
- Nonsyndromic genetic hearing loss, also linked to GJB2
- Hearing loss, also linked to GJB2
- Monogenic hearing loss, also linked to GJB2
- Autosomal dominant keratitis-ichthyosis-hearing loss syndrome, also linked to GJB2
- Ichthyosis, hystrix-like, with hearing loss, also linked to GJB2
- Palmoplantar keratoderma-deafness syndrome, also linked to GJB2
- Knuckle pads, deafness AND leukonychia syndrome, also linked to GJB2
- Deafness, also linked to GJB2
Frequently asked questions
Which genes are linked to Mutilating keratoderma?
In CATVariant, Mutilating keratoderma is linked to 1 analyzed protein: GJB2 (Gap junction beta-2 protein).
How many genetic variants are linked to Mutilating keratoderma?
28 variants: 15 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 11 are of uncertain significance or have conflicting reports.
Which uncertain variants in Mutilating keratoderma 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 Mutilating keratoderma?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.93, based on 15 disease-causing and 9 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center