GeneBe

PDZD7

protein-coding

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

Gene summary

This gene encodes a ciliary protein homologous to proteins which are mutated in Usher syndrome patients, and mutations and translocations involving this gene have been associated with two types of Usher syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

Previous symbols:
  • PDZK7
  • DFNB57

MANE transcript

NM_001195263.2

Inheritance

AR, Digenic

ClinVar variants

P:128U:536B:297

Top phenotype

Deafness, autosomal recessive 57; Usher syndrome, type IIC

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr10:101,007,679-101,032,295

External References & Databases

Ensembl (ENSG00000186862)NCBI Gene (79955)OMIM (612971)HGNC:26257GenCCUniProt (Q9H5P4)AlphaFoldClinVar (PDZD7)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~24.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: PanelApp Australia

hearing loss, autosomal recessive 57STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033201

Submitter: Labcorp Genetics (formerly Invitae)

Usher syndrome type 2CLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0011558

Submitter: Labcorp Genetics (formerly Invitae)

hearing loss, autosomal recessiveDEFINITIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0019588

Submitter: ClinGen

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 57; Usher syndrome, type IICAR/Digenic

Manifestation: Audiologic/Otolaryngologic; Ophthalmologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Comments: For Usher syndrome, type IIc, digenic inheritance (with GRP98) has been described

Refs: 19028668; 20440071; 26416264; 26849169; 29048736Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDZD7 variants in ClinVar

18 Conditions Cataloged
not providedTotal: 1038
not specifiedTotal: 143
PDZD7-related disorderTotal: 109
Inborn genetic diseasesTotal: 88
Hearing loss, autosomal recessive 57Total: 55
Usher syndrome type 2CTotal: 21
Usher syndrome type 2ATotal: 19
Hearing impairmentTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001195263.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
263
clinvar
4
clinvar
 270
missense
2
clinvar
7
clinvar
517
clinvar
29
clinvar
1
clinvar
 556
nonsense
15
clinvar
13
clinvar
2
clinvar
 30
start loss
1
clinvar
 1
frameshift
40
clinvar
36
clinvar
12
clinvar
 88
splice donor/acceptor (+/-2bp)
2
clinvar
13
clinvar
1
clinvar
 16
Total59695362925961

Highest pathogenic variant AF is 0.00044869975

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001195263.2RefSeqNP_001182192.116MANE Select
ENST00000619208.6EnsemblENSP00000480489.116MANE Select
NM_001351044.2RefSeqNP_001337973.19Standard
NM_001437429.1RefSeqNP_001424358.116Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
pdzd7aDanio rerio

Structure: eye photoreceptor cell

Quality: apoptotic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

Molecular Function

  • protein binding
  • protein homodimerization activity
  • protein heterodimerization activity

Cellular Component

  • photoreceptor inner segment
  • stereocilia ankle link
  • stereocilia ankle link complex
  • extracellular space
  • nucleus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000370215
Coding exons
9
Length
23451
Individuals with no LoFs
125708
Homozygous LoFs
0
Heterozygous LoFs
40
Defined
125748
p
0.000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.3723493301.060.00002163277
Missense (PolyPhen)114119.370.955011166
Synonymous0.3241341390.9650.000009021109
Loss of Function1.071722.50.7560.00000136227

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000720.000062rare
Latino/Admixed American0.0000890.000087rare
Ashkenazi Jewish00.0absent
East Asian0.000230.00022rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000140.00014rare
South Asian0.000460.00046rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.567

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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