PDZD7

PDZ domain containing 7, the group of PDZ domain containing|USH2 complex

Basic information

Region (hg38): 10:101007679-101032295

Previous symbols: [ "PDZK7", "DFNB57" ]

Links

ENSG00000186862

∙ NCBI:79955 ∙ OMIM:612971 ∙ HGNC:26257 ∙ Uniprot:Q9H5P4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hearing loss, autosomal recessive 57 (Strong), mode of inheritance: AR
hearing loss, autosomal recessive 57 (Strong), mode of inheritance: AR
Usher syndrome type 2C (Limited), mode of inheritance: Unknown
hearing loss, autosomal recessive (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 57; Usher syndrome, type IIC	AR/Digenic	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	19028668; 20440071; 26416264; 26849169; 29048736
For Usher syndrome, type IIc, digenic inheritance (with GRP98) has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDZD7 gene.

not_provided (968 variants)
Inborn_genetic_diseases (81 variants)
not_specified (44 variants)
Hearing_loss,_autosomal_recessive_57 (42 variants)
PDZD7-related_disorder (26 variants)
Usher_syndrome_type_2C (14 variants)
Usher_syndrome_type_2A (12 variants)
Hearing_impairment (9 variants)
Retinal_dystrophy (8 variants)
Usher_syndrome,_type_IIC,_GPR98/PDZD7_digenic (3 variants)
Hearing_loss,_autosomal_recessive (3 variants)
Usher_syndrome (2 variants)
Rare_genetic_deafness (1 variants)
Deafness (1 variants)
Nonsyndromic_genetic_hearing_loss (1 variants)
Ear_malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDZD7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001195263.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		3 clinvar	241 clinvar	4 clinvar	249
missense	2 clinvar	4 clinvar	485 clinvar	21 clinvar	3 clinvar	515
nonsense	16 clinvar	5 clinvar	1 clinvar			22
start loss			1			1
frameshift	46 clinvar	16 clinvar	9 clinvar			71
splice donor/acceptor (+/-2bp)	2 clinvar	10 clinvar	1 clinvar			13
Total	67	35	500	262	7

Highest pathogenic variant AF is 0.000880671

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDZD7	protein_coding	protein_coding	ENST00000370215	9	23451

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.64e-10	0.453	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.372	349	330	1.06	0.0000216	3277
Missense in Polyphen		114	119.37	0.95501		1166
Synonymous	0.324	134	139	0.965	0.00000902	1109
Loss of Function	1.07	17	22.5	0.756	0.00000136	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000161	0.000150
Ashkenazi Jewish	0.00	0.00
East Asian	0.000226	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000143	0.000141
Middle Eastern	0.000226	0.000217
South Asian	0.000460	0.000457
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Disease: 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 mutations affecting distinct genetic loci, including the gene represented in this entry. A PDZD7 mutation has been found in combination with a mutation in GPR98 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.;

Recessive Scores

pRec: 0.110

Intolerance Scores

loftool: 0.616
rvis_EVS: -0.36
rvis_percentile_EVS: 29.31

Haploinsufficiency Scores

pHI: 0.240
hipred: Y
hipred_score: 0.640
ghis: 0.599

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.567

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Pdzd7
Phenotype: cellular phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: pdzd7a
Affected structure: eye photoreceptor cell
Phenotype tag: abnormal
Phenotype quality: apoptotic

Gene ontology

Biological process: sensory perception of sound;establishment of protein localization;detection of mechanical stimulus involved in sensory perception of sound;auditory receptor cell stereocilium organization;auditory receptor cell development
Cellular component: photoreceptor inner segment;stereocilia ankle link;stereocilia ankle link complex;extracellular space;nucleus;plasma membrane;cilium;photoreceptor connecting cilium;stereocilium;stereocilium tip;USH2 complex
Molecular function: protein binding;protein homodimerization activity;protein heterodimerization activity