Monogenic hearing loss

Gene: CD164

Green List (high evidence)

Comment on list classification: There are now more than 3 unrelated families of various ancestries with the same heterozygous CD164 variant (p.Arg192Ter), which segregates in a dominant fashion with bilateral progressive hearing loss. There is also some supportive evidence from HEK cells and mouse expression studies. Hence, this gene can be promoted to Green for Monogenic hearing loss.

Created: 9 Jun 2026, 3:41 p.m. | Last Modified: 2 Oct 2026, 3:01 p.m.

Panel Version: 6.43

PMID: 35254497 Oziębło et al., 2022
Family 1 - large Polish pedigree with AD progressive hearing loss; CD164: c.574C>T, p.Arg192Ter segregated in affected individuals
Family 2 - Korean family, 25 yo proband with bilateral progressive hearing loss onset around 22 years old; also het for CD164 p.Arg192Ter
Same variant as reported in PMID 26197441 Nyegaard et al (2015) in a Danish family with hearing loss - recurrent hot spot mutation?
CD164: c.574C>T, p.Arg192Ter - only 2 hets reported in gnomAD v4.1.1, MAF = 0.000001696
Age of onset of hearing loss for all 3 families ranged from newborn stage to adulthood.

PMID: 36454368 Moresco et al., 2023
Family 7 - AD nonsyndromic hearing loss, affected individuals harboured het CD164: c.574C>T, p.Arg192Ter variant - segregated with disease. Seq method: Trio WES.

Functional evidence: PMID: 26197441 - Nyegaard et al (2015):
Functional studies in HEK cells demonstrated that the truncated p.Arg192Ter protein was almost completely retained on the plasma cell membrane in contrast to the WT protein, which targeted primarily to the endo-lysosomal compartments, implicating failed endocytosis as a possible disease mechanism.
In addition, CD164 was found to be expressed in the mouse ear, in the inner and outer hair cells of the organ of Corti, as well as in other locations in the cochlear duct.

The assocation between CD164 and autosomal dominant nonsyndromic hearing loss has been classified as Moderate by ClinGen Hearing Loss GCEP in 2024.

Created: 9 Jun 2026, 3:36 p.m. | Last Modified: 2 Oct 2026, 3 p.m.

Panel Version: 6.43

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Deafness, autosomal dominant 66, OMIM:616969

Publications

• 26197441
• 35254497
• 36454368

Red List (low evidence)

Included in our current panel, no class 4 or 5 variants identified. One nonsense variant in literature Nyegaard et al (2015) PMID 26197441

Created: 17 Feb 2019, 4:35 p.m.

Publications

• 26197441

Added at suggestion of Emma Ashton, GOSH
Sources: Expert list

Created: 17 Feb 2019, 4:31 p.m.

Mode of inheritance
Unknown