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CLRN2
clarin 2
CLRN2 is located on the short (p) arm of chromosome 4, at band 4p15.32. Arm ratio per GRCh38 - banding schematic.
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Overview
CLRN2 is located on chromosome 4 and produces a member of the clarin protein family. Clarins are believed to be involved in the organisation of specialised membrane structures within sensory cells of the inner ear. The gene is expressed during development and in adult auditory tissue, suggesting ongoing roles in hearing function.
Pathogenic changes in CLRN2 typically follow an autosomal recessive inheritance pattern, meaning two altered copies are generally required for a condition to manifest. Individuals with one pathogenic variant are carriers and usually do not experience hearing loss themselves. Research into CLRN2 remains relatively early-stage compared to more extensively studied hearing-loss genes.
What the gene does
Clarin 2 is thought to contribute to the structural integrity of hair cells in the cochlea, the spiral-shaped organ of the inner ear that converts sound vibrations into electrical signals. Hair cells contain specialised projections called stereocilia, which are arranged in bundles and deflect in response to sound waves.
Evidence suggests that clarin proteins may help organise the protein complexes at the base of stereocilia, supporting proper mechanotransduction-the process by which mechanical stimuli are converted into nerve impulses. Clarin 2 may also participate in cellular trafficking pathways that deliver essential proteins to the correct locations within hair cells. While the precise molecular mechanisms remain under investigation, disruption of clarin 2 function appears to compromise the ability of hair cells to detect and transmit auditory information effectively.
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Chromosome location
CLRN2 is situated on the short arm of chromosome 4 at band p15.32. This chromosomal region contains multiple genes, and the precise genomic context may influence regulatory elements that control when and where CLRN2 is expressed. The gene comprises several exons encoding a relatively compact protein of 232 amino acids.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. Clarin 2 is predicted to contain multiple transmembrane segments, consistent with a role as an integral membrane protein embedded within cellular structures. Computational models suggest the protein may adopt a configuration that allows it to interact with other membrane-associated proteins, though experimental validation of these structural features is ongoing.
Key variants
Pathogenic variants in CLRN2 have been identified in families with autosomal recessive hearing loss. These variants include missense changes that alter single amino acids, as well as nonsense and frameshift variants predicted to truncate the protein or trigger nonsense-mediated decay. The rarity of CLRN2-related hearing loss means that variant databases contain relatively few entries compared to more common hearing-loss genes, and functional characterisation of individual variants is limited.
Sample of pathogenic variants
1 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.494C>A | p.Thr165Lys | Pathogenic | - | Hearing loss, autosomal recessive 117 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in CLRN2 are associated with non-syndromic hearing loss, meaning affected individuals typically experience hearing impairment without additional clinical features affecting other organ systems. The severity and age of onset can vary, with some individuals presenting with congenital hearing loss while others may develop symptoms later in childhood. Because CLRN2-related hearing loss is rare, comprehensive genotype-phenotype correlations are still emerging as additional cases are reported in the medical literature.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic CLRN2 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
Frequently asked questions
What does it mean to be a carrier of a CLRN2 variant?
A carrier has one pathogenic variant and one typical copy of the gene. Carriers generally do not experience hearing loss themselves but can pass the variant to their children. If both parents are carriers, each child has a 25% chance of inheriting two pathogenic variants and potentially developing hearing impairment.
How is CLRN2-related hearing loss diagnosed?
Diagnosis typically involves audiological testing to assess hearing function, followed by genetic testing to identify pathogenic variants in CLRN2. Because this gene is less commonly implicated than others, clinicians may use comprehensive hearing-loss gene panels to screen multiple candidates simultaneously.
Can CLRN2 variants cause progressive hearing loss?
Some evidence suggests that hearing loss associated with CLRN2 variants may be stable, while other reports describe progressive decline. The natural history varies among affected individuals, and long-term audiological monitoring is often recommended to track any changes in hearing over time.