Monogenic hearing loss

Gene: CLRN2

Green List (high evidence)

Comment on list classification: There are now 2 unrelated families reported with biallelic CLRN2 variants and non-syndromic hearing loss. Mouse model supports this association, as mice homozygous for a deletion in Clrn2 exhibit a severe-to-profound hearing loss. Hence, this gene can now be promoted to Green at the next update.

Created: 10 Jun 2026, 8:05 a.m. | Last Modified: 10 Jun 2026, 8:05 a.m.

Panel Version: 6.22

PMID: 39446282 Ahmad et al., 2025
Consanguineous family, 2 sibs with non-syndromic profound hearing loss, homozygous for CLRN2: c.414C>A, p.Cys138*. Seq method: WES + Sanger. Variant has 1 allele reported in gnomAD (no homozygotes). Parents both heterozygous for the variant and unaffected.

PMID: 33496845 Vona et al 2021
Iranian family, where homozygous CLRN2: c.494C > A, p.Thr165Lys variant (expected to result in p.(Gly146Lysfs*26)) change) segregated with non-syndromic hearing loss.
Clrn2 mouse mutant, in which exon 2 has been deleted (Clrn2del629). Clrn2del629/del629 mice exhibit a severe-to-profound hearing loss affecting all frequencies tested.

The association between CLRN2 and AR nonsyndromic genetic hearing loss was classified as Moderate in ClinGen (Hearing Loss GCEP, Sept 2025).

Created: 10 Jun 2026, 7:59 a.m. | Last Modified: 10 Jun 2026, 8:08 a.m.

Panel Version: 6.22

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 117, OMIM:619174; hearing loss, autosomal recessive 117, MONDO:0030905

Publications

• 39446282

I don't know

Comment on list classification: Promoting this gene from grey to amber as there is one extended family reported with variants in this gene, plus some supporting functional data.

Created: 9 Jun 2021, 4:22 p.m. | Last Modified: 9 Jun 2021, 4:22 p.m.

Panel Version: 2.168

Provisionally associated with ?Deafness, autosomal recessive 117 #619174 (AR) in OMIM.

As Zornitza Stark reports PMID: 33496845 (Vona et al 2021) describes an extended Iranian consanguineous family with a homozygous missense variant in CLRN2 that segregates with non-syndromic hearing loss in the family. Identified by homozygosity mapping and then exome sequencing. in vitro RNA splicing assays demonstrate an effect on splicing and functional studies support a role in hearing.

Created: 9 Jun 2021, 4:21 p.m. | Last Modified: 9 Jun 2021, 4:21 p.m.

Panel Version: 2.166

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 117, OMIM:619174; deafness, autosomal recessive 117, MONDO:0030905

Publications

• 33496845

I don't know

Missense variant segregates with non-syndromic hearing loss in 3 members of a consanguineous family, two from one nuclear family and one from another. The variant was also shown to result in some transcripts being abnormally spliced, resulting in a premature stop codon.

Functional studies in zebrafish and mice show the gene plays an essential role in normal organization and maintenance of the auditory hair bundles, and for hearing function.

Rated Amber due to supporting functional studies in mice.
Sources: Literature

Created: 1 Feb 2021, 10:52 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Non-syndromic hearing loss

Publications

• 33496845