PDZD7

Chr 10ARDigenic dominant

PDZ domain containing 7

Also known as: DFNB57, PDZK7

NCBI Gene: 79955 ENSG00000186862 UniProt: Q9H5P4 OMIM: 612971

This gene encodes a ciliary protein essential for organizing the USH2 complex at stereocilia ankle links in cochlear hair cells and blocks inhibition of adenylate cyclase activity mediated by ADGRV1. Mutations cause autosomal recessive deafness and Usher syndrome type IIC (involving both hearing loss and vision loss), with some cases showing digenic inheritance patterns involving GPR98. The gene shows low constraint against loss-of-function variants and primarily affects sensory organs.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAR/Digenic dominantLOEUF 1.133 OMIM phenotypes

Clinical Summary— PDZD7

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Gene-Disease Validity (ClinGen)

hearing loss, autosomal recessive · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

105 unique Pathogenic / Likely Pathogenic· 547 VUS of 1130 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PDZD7

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 1.07

OE 0.76 (0.52–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.37Z-score

OE missense 1.06 (0.97–1.16)

349 obs / 330.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.76 (0.52–1.13)

0≤0.351.4

Missense OE?1.06 (0.97–1.16)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 17 / 22.5Missense obs/exp: 349 / 330.0Syn Z: 0.32

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPDZD7-related Usher syndrome, GPR98/PDZD7 digenicLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6357th %ile

GOF

0.6737th %ile

LOF

0.50top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

1130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic71

Likely Pathogenic34

VUS547

Likely Benign383

Benign56

Conflicting28

Pathogenic

Likely Pathogenic

547

VUS

383

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	68	2	1	0	71
Likely Pathogenic	32	2	0	0	34
VUS	12	522	9	4	547
Likely Benign	0	25	119	239	383
Benign	0	8	42	6	56
Conflicting	—				28
Total	112	559	171	249	1,119

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap PDZD7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →