UniProt functional annotation for Q9H5P4



	UniProt functional annotation for Q9H5P4

UniProt code: Q9H5P4.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: In cochlear developing hair cells, essential in organizing the USH2 complex at stereocilia ankle links. Blocks inhibition of adenylate cyclase activity mediated by ADGRV1. {ECO:0000250|UniProtKB:E9Q9W7}.

Subunit: Homodimerizes (via PDZ2 domain). Component of USH2 complex, composed of ADGRV1, PDZD7, USH2A and WHRN. Interacts (via PDZ domains) with WHRN; the interaction is direct (By similarity). Interacts with USH1G (PubMed:19028668). Interacts with ADGRV1 (via the cytoplasmic region) (PubMed:20440071). Interacts with USH2A (via the cytoplasmic region) (PubMed:20440071). Interacts with MYO7A (via MyTH4-FERM domains) (By similarity). {ECO:0000250|UniProtKB:E9Q9W7, ECO:0000269|PubMed:19028668, ECO:0000269|PubMed:20440071}.

Subcellular location: Cell projection, cilium {ECO:0000269|PubMed:20440071}. Nucleus {ECO:0000269|PubMed:20440071}. Cell projection, stereocilium {ECO:0000250|UniProtKB:E9Q9W7}. Note=Localizes at the ankle region of the stereocilia. {ECO:0000250|UniProtKB:E9Q9W7}.

Tissue specificity: Weakly expressed in the inner ear. Expressed in the retinal pigment epithelium. {ECO:0000269|PubMed:19028668, ECO:0000269|PubMed:20440071}.

Disease: Deafness, autosomal recessive, 57 (DFNB57) [MIM:618003]: A form of non-syndromic, sensorineural deafness characterized by symmetric, bilateral hearing loss with onset in early childhood. Vestibular function is preserved. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB57 severity ranges from moderate to severe. {ECO:0000269|PubMed:19028668, ECO:0000269|PubMed:26416264, ECO:0000269|PubMed:26849169, ECO:0000269|PubMed:29048736}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=A chromosomal aberration disrupting PDZD7 has been found in patients with non-syndromic sensorineural deafness. Translocation t(10;11),t(10;11). {ECO:0000269|PubMed:19028668}.

Disease: Usher syndrome 2C (USH2C) [MIM:605472]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. {ECO:0000269|PubMed:20440071}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. A PDZD7 mutation has been found in combination with a mutation in ADGRV1 in a patient affected by Usher syndrome, suggesting PDZD7 mutations contribute to digenic Usher syndrome. {ECO:0000269|PubMed:20440071}.

Disease: Usher syndrome 2A (USH2A) [MIM:276901]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. {ECO:0000269|PubMed:20440071}. Note=The gene represented in this entry acts as a disease modifier.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		In cochlear developing hair cells, essential in organizing the USH2 complex at stereocilia ankle links. Blocks inhibition of adenylate cyclase activity mediated by ADGRV1. {ECO:0000250\|UniProtKB:E9Q9W7}.


Subunit:		Homodimerizes (via PDZ2 domain). Component of USH2 complex, composed of ADGRV1, PDZD7, USH2A and WHRN. Interacts (via PDZ domains) with WHRN; the interaction is direct (By similarity). Interacts with USH1G (PubMed:19028668). Interacts with ADGRV1 (via the cytoplasmic region) (PubMed:20440071). Interacts with USH2A (via the cytoplasmic region) (PubMed:20440071). Interacts with MYO7A (via MyTH4-FERM domains) (By similarity). {ECO:0000250\|UniProtKB:E9Q9W7, ECO:0000269\|PubMed:19028668, ECO:0000269\|PubMed:20440071}.
Subcellular location:		Cell projection, cilium {ECO:0000269\|PubMed:20440071}. Nucleus {ECO:0000269\|PubMed:20440071}. Cell projection, stereocilium {ECO:0000250\|UniProtKB:E9Q9W7}. Note=Localizes at the ankle region of the stereocilia. {ECO:0000250\|UniProtKB:E9Q9W7}.
Tissue specificity:		Weakly expressed in the inner ear. Expressed in the retinal pigment epithelium. {ECO:0000269\|PubMed:19028668, ECO:0000269\|PubMed:20440071}.
Disease:		Deafness, autosomal recessive, 57 (DFNB57) [MIM:618003]: A form of non-syndromic, sensorineural deafness characterized by symmetric, bilateral hearing loss with onset in early childhood. Vestibular function is preserved. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB57 severity ranges from moderate to severe. {ECO:0000269\|PubMed:19028668, ECO:0000269\|PubMed:26416264, ECO:0000269\|PubMed:26849169, ECO:0000269\|PubMed:29048736}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=A chromosomal aberration disrupting PDZD7 has been found in patients with non-syndromic sensorineural deafness. Translocation t(10;11),t(10;11). {ECO:0000269\|PubMed:19028668}.
Disease:		Usher syndrome 2C (USH2C) [MIM:605472]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. {ECO:0000269\|PubMed:20440071}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. A PDZD7 mutation has been found in combination with a mutation in ADGRV1 in a patient affected by Usher syndrome, suggesting PDZD7 mutations contribute to digenic Usher syndrome. {ECO:0000269\|PubMed:20440071}.
Disease:		Usher syndrome 2A (USH2A) [MIM:276901]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. {ECO:0000269\|PubMed:20440071}. Note=The gene represented in this entry acts as a disease modifier.