PDZD7

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

Basic information

Region (hg38): 10:101007678-101032295

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 (893 variants)
• not specified (53 variants)
• Hearing loss, autosomal recessive 57 (31 variants)
• Inborn genetic diseases (27 variants)
• Usher syndrome type 2C (9 variants)
• Hearing impairment (7 variants)
• Usher syndrome type 2A;Hearing loss, autosomal recessive 57;Usher syndrome type 2C (4 variants)
• PDZD7-related condition (4 variants)
• Usher syndrome type 2C;Usher syndrome type 2A;Hearing loss, autosomal recessive 57 (3 variants)
• Usher syndrome (2 variants)
• Usher syndrome type 2A (2 variants)
• Usher syndrome, type IIC, GPR98/PDZD7 digenic;Hearing loss, autosomal recessive 57 (1 variants)
• Hearing loss, autosomal recessive (1 variants)
• PDZD7-Related Disorders (1 variants)
• Ear malformation (1 variants)
• Hearing loss, autosomal recessive 57;Usher syndrome type 2C;Usher syndrome type 2A (1 variants)
• Usher syndrome, type IIC, GPR98/PDZD7 digenic (1 variants)
• Rare genetic deafness (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	185	6	194
missense	2	2	436	8	7	455
nonsense	9	5	2			16
start loss			1			1
frameshift	27	8	10			45
inframe indel			25	5	1	31
splice donor/acceptor (+/-2bp)	1	6	1			8
splice region			11	17	1	29
non coding			4	74	40	118
Total	39	21	482	272	54

Highest pathogenic variant AF is 0.000694

Variants in PDZD7

This is a list of pathogenic ClinVar variants found in the PDZD7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-101008423-C-T			Likely benign (Feb 23, 2021)
10-101008471-G-A			Uncertain significance (Oct 04, 2022)
10-101008472-G-A			Uncertain significance (Apr 18, 2022)
10-101008477-C-T		not specified	Benign (Jan 31, 2024)
10-101008478-G-A			Uncertain significance (Aug 19, 2022)
10-101008486-G-T			Uncertain significance (Aug 20, 2022)
10-101008490-C-T			Uncertain significance (Nov 13, 2023)
10-101008491-G-A		not specified	Benign/Likely benign (Oct 03, 2023)
10-101008496-T-C			Uncertain significance (Jan 14, 2022)
10-101008496-TAGAATC-T			Uncertain significance (Apr 20, 2021)
10-101008506-AGTCT-A			Uncertain significance (May 25, 2021)
10-101008507-G-A			Uncertain significance (Apr 26, 2022)
10-101008523-AG-A			Uncertain significance (Feb 12, 2020)
10-101008524-G-A			Likely benign (Jul 03, 2023)
10-101008526-G-A			Uncertain significance (Sep 27, 2022)
10-101008539-A-C			Likely benign (Oct 17, 2022)
10-101008542-TG-T			Uncertain significance (Nov 28, 2022)
10-101008545-C-T			Likely benign (Jul 16, 2023)
10-101008546-TGGAGGAGCCTGGCATCAGTG-T			Uncertain significance (Nov 27, 2023)
10-101008548-G-A			Likely benign (Aug 16, 2022)
10-101008554-C-G			Uncertain significance (Jul 12, 2022)
10-101008554-C-CCTGGCATCAGAGGGAGGAGT			Uncertain significance (Jul 25, 2022)
10-101008570-G-A			Uncertain significance (Aug 06, 2022)
10-101008571-G-C			Uncertain significance (Aug 14, 2021)
10-101008575-CTG-C			Uncertain significance (Jun 13, 2022)

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