Deafness: genes and variants

Genes linked to Deafness

• MYO7A: Unconventional myosin-VIIa

  Its actin-based motor supports stereocilia organization in inner-ear hair cells and transport processes in retinal cells. Biallelic pathogenic variants cause Usher syndrome type 1B, while other alleles can cause nonsyndromic hearing loss.

  2 disease-causing and 0 uncertain variants in MYO7A are linked to Deafness.

• SLC26A4: Pendrin

  SLC26A4, known as pendrin, is an anion exchanger that transports chloride, iodide, and bicarbonate without directly using sodium. It supports ion balance in the inner ear and thyroid, and SLC26A4 variants cause Pendred syndrome and inherited deafness.

  2 disease-causing and 0 uncertain variants in SLC26A4 are linked to Deafness.

• TECTA: Alpha-tectorin

  Its extracellular matrix organizes the tectorial membrane that mechanically couples sound-induced motion to cochlear hair cells. Dominant or recessive pathogenic variants cause nonsyndromic hearing loss, with characteristic frequency patterns depending on the affected region.

  1 disease-causing and 0 uncertain variants in TECTA are linked to Deafness.

• 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.

  1 disease-causing and 0 uncertain variants in GJB2 are linked to Deafness.

• OTOF: Otoferlin

  It couples calcium entry to synaptic-vesicle fusion at inner hair-cell ribbon synapses, enabling rapid transmission of acoustic signals to the auditory nerve. Biallelic loss-of-function variants cause DFNB9 auditory neuropathy or nonsyndromic sensorineural hearing loss.

  0 disease-causing and 0 uncertain variants in OTOF are linked to Deafness.

• USH1C: Harmonin

  It organizes protein complexes in inner-ear hair-cell stereocilia and photoreceptor structures. Biallelic pathogenic variants cause Usher syndrome type 1C with congenital severe hearing loss and progressive retinitis pigmentosa, or in some alleles isolated deafness.

  0 disease-causing and 0 uncertain variants in USH1C are linked to Deafness.

• CLDN14: Claudin-14

  0 disease-causing and 0 uncertain variants in CLDN14 are linked to Deafness.

• PCDH15: Protocadherin-15

  It forms part of the tip-link complex that converts mechanical deflection of inner-ear hair bundles into electrical signals and also supports photoreceptor structure. Biallelic pathogenic variants cause Usher syndrome type 1F or nonsyndromic hearing loss.

  0 disease-causing and 0 uncertain variants in PCDH15 are linked to Deafness.

• MCM2: DNA replication licensing factor MCM2

  It is part of the MCM2-7 helicase that unwinds DNA at replication forks and licenses origins before S phase. Excess or dysregulated expression is common in proliferative cancers and is widely used as a marker of active DNA replication.

  0 disease-causing and 0 uncertain variants in MCM2 are linked to Deafness.

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

Known disease-causing variants in Deafness

Same protein, different disease

• Usher syndrome is also caused by MYO7A variants; they fall mostly in different places as the Deafness variants (80 disease-causing).
• Autosomal recessive nonsyndromic hearing loss 4 is also caused by MYO7A variants; they fall mostly in different places as the Deafness variants (26 disease-causing).
• Rare genetic deafness is also caused by MYO7A variants; they fall mostly in different places as the Deafness variants (23 disease-causing).
• Autosomal dominant nonsyndromic hearing loss is also caused by MYO7A variants; they fall mostly in different places as the Deafness variants (13 disease-causing).
• Nonsyndromic genetic hearing loss is also caused by MYO7A variants; they fall mostly in different places as the Deafness variants (4 disease-causing).
• Pendred syndrome is also caused by SLC26A4 variants; they fall mostly in different places as the Deafness variants (106 disease-causing).
• Autosomal recessive nonsyndromic hearing loss 4 is also caused by SLC26A4 variants; they fall mostly in different places as the Deafness variants (106 disease-causing).
• Rare genetic deafness is also caused by SLC26A4 variants; they fall mostly in different places as the Deafness variants (14 disease-causing).
• Monogenic hearing loss is also caused by SLC26A4 variants; they fall mostly in different places as the Deafness variants (6 disease-causing).
• Autosomal dominant nonsyndromic hearing loss is also caused by TECTA variants; they fall mostly in different places as the Deafness variants (15 disease-causing).
• Rare genetic deafness is also caused by TECTA variants; they fall mostly in different places as the Deafness variants (3 disease-causing).
• Autosomal recessive nonsyndromic hearing loss 4 is also caused by GJB2 variants; they fall mostly in different places as the Deafness variants (38 disease-causing).
• Nonsyndromic genetic hearing loss is also caused by GJB2 variants; they fall mostly in different places as the Deafness variants (28 disease-causing).
• Rare genetic deafness is also caused by GJB2 variants; they fall mostly in different places as the Deafness variants (25 disease-causing).
• Mutilating keratoderma is also caused by GJB2 variants; they fall mostly in different places as the Deafness variants (15 disease-causing).
• Ichthyosis, hystrix-like, with hearing loss is also caused by GJB2 variants; they fall mostly in different places as the Deafness variants (13 disease-causing).

Diseases related to Deafness

• Autosomal recessive nonsyndromic hearing loss 4, also linked to CLDN14, GJB2, MYO7A, OTOF and 4 more
• Hearing loss, also linked to CLDN14, GJB2, MYO7A, OTOF and 4 more
• Rare genetic deafness, also linked to GJB2, MYO7A, OTOF, PCDH15 and 2 more
• Autosomal dominant nonsyndromic hearing loss, also linked to GJB2, MCM2, MYO7A and TECTA
• Nonsyndromic genetic hearing loss, also linked to GJB2, MYO7A, OTOF and TECTA
• Monogenic hearing loss, also linked to GJB2, MYO7A, SLC26A4 and TECTA
• Usher syndrome, also linked to MYO7A, PCDH15 and USH1C
• Auditory neuropathy, also linked to MYO7A and OTOF
• Retinitis pigmentosa, also linked to MYO7A
• RASopathy, also linked to SLC26A4
• Noonan syndrome, also linked to GJB2
• Pendred syndrome, also linked to SLC26A4

Frequently asked questions

Which genes are linked to Deafness?

In CATVariant, Deafness is linked to 9 analyzed proteins: MYO7A (Unconventional myosin-VIIa), SLC26A4 (Pendrin), TECTA (Alpha-tectorin), GJB2 (Gap junction beta-2 protein), OTOF (Otoferlin), USH1C (Harmonin) and 3 more.

How many genetic variants are linked to Deafness?

116 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 0 are of uncertain significance or have conflicting reports.

Which uncertain variants in Deafness look disease-causing?

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

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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