Hearing loss, autosomal recessive 57

Summary

Hearing loss, autosomal recessive 57 (MONDO:0033201) is a disease caused by PDZD7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PDZD7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 53

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal recessive 57
Mondo ID	MONDO:0033201
OMIM	618003
DOID	DOID:0111635
UMLS	C4693893
MedGen	1631180
GARD	0025788
Is cancer (heuristic)	no

Also known as: deafness, autosomal recessive 57 · DFNB57 · hearing loss, autosomal recessive 57

Data availability: 53 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › hearing loss, autosomal recessive › hearing loss, autosomal recessive 57

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

53 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 8 benign, 8 pathogenic, 8 likely pathogenic, 7 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1324872	NM_001195263.2(PDZD7):c.1543C>T (p.Gln515Ter)	PDZD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455175	NM_001195263.2(PDZD7):c.918dup (p.Leu307fs)	PDZD7	Pathogenic	criteria provided, multiple submitters, no conflicts
1806296	NM_001195263.2(PDZD7):c.668del (p.Gly223fs)	PDZD7	Pathogenic	criteria provided, single submitter
30983	NM_001195263.2(PDZD7):c.166dup (p.Arg56fs)	PDZD7	Pathogenic	criteria provided, multiple submitters, no conflicts
3343896	NM_001195263.2(PDZD7):c.1933+1G>A	PDZD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601632	NM_001195263.2(PDZD7):c.2136del (p.Ile714fs)	PDZD7	Pathogenic	criteria provided, single submitter
545399	NM_001195263.2(PDZD7):c.307G>C (p.Gly103Arg)	PDZD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545402	NM_001195263.2(PDZD7):c.1576C>T (p.Gln526Ter)	PDZD7	Pathogenic	no assertion criteria provided
545404	NM_001195263.2(PDZD7):c.1648C>T (p.Gln550Ter)	PDZD7	Pathogenic	criteria provided, multiple submitters, no conflicts
545407	NM_001195263.2(PDZD7):c.1207del (p.His403fs)	PDZD7	Pathogenic	no assertion criteria provided
915843	NM_001195263.2(PDZD7):c.2089del (p.Ala697fs)	PDZD7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
992657	NM_001195263.2(PDZD7):c.251T>C (p.Ile84Thr)	PDZD7	Pathogenic	criteria provided, single submitter
1499226	NM_001195263.2(PDZD7):c.928+1G>A	PDZD7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136926	NM_001195263.2(PDZD7):c.1750-2A>G	PDZD7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601633	NM_001195263.2(PDZD7):c.2368_2377del (p.Lys790fs)	PDZD7	Likely pathogenic	criteria provided, single submitter
3765544	NM_001195263.2(PDZD7):c.1788_1801del (p.Leu597fs)	PDZD7	Likely pathogenic	criteria provided, single submitter
3777239	NM_001195263.2(PDZD7):c.1183_1184dup (p.Ala396fs)	PDZD7	Likely pathogenic	criteria provided, single submitter
4849468	NM_001195263.2(PDZD7):c.1798del (p.Ile600fs)	PDZD7	Likely pathogenic	criteria provided, single submitter
545400	NM_001195263.2(PDZD7):c.854T>G (p.Met285Arg)	PDZD7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
545401	NM_001195263.2(PDZD7):c.1500C>A (p.Tyr500Ter)	PDZD7	Likely pathogenic	criteria provided, single submitter
1396533	NM_001195263.2(PDZD7):c.2796_2798del (p.Arg933del)	PDZD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44121	NM_001195263.2(PDZD7):c.2107del (p.Ser703fs)	PDZD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44131	NM_001195263.2(PDZD7):c.2672AGA[1] (p.Lys892del)	PDZD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
545403	NM_001195263.2(PDZD7):c.682G>A (p.Gly228Arg)	PDZD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
666906	NM_001195263.2(PDZD7):c.490C>T (p.Arg164Trp)	PDZD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
666909	NM_001195263.2(PDZD7):c.2319TAGCCGCAGCCG[1] (p.773RS[4])	PDZD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
955403	NM_001195263.2(PDZD7):c.2850del (p.Ser953fs)	PDZD7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1010618	NM_001195263.2(PDZD7):c.2515C>T (p.Pro839Ser)	PDZD7	Uncertain significance	criteria provided, single submitter
1039923	NM_001195263.2(PDZD7):c.598G>A (p.Asp200Asn)	PDZD7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1341337	NM_001195263.2(PDZD7):c.2353A>C (p.Ser785Arg)	PDZD7	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PDZD7	Definitive	Unknown	hearing loss, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDZD7	Orphanet:231178	Usher syndrome type 2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PDZD7	HGNC:26257	ENSG00000186862	Q9H5P4	PDZ domain-containing protein 7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDZD7	PDZ domain-containing protein 7	In cochlear developing hair cells, essential in organizing the USH2 complex at stereocilia ankle links.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PDZD7	Scaffold/PPI	no		PDZ, PDZ_sf, PDZD7_HN-like

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDZD7	178	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDZD7	1,317

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDZD7	Q9H5P4	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
inner ear receptor cell differentiation	1	3370.4×	0.002	PDZD7
auditory receptor cell development	1	1872.4×	0.002	PDZD7
detection of mechanical stimulus involved in sensory perception of sound	1	936.2×	0.002	PDZD7
auditory receptor cell stereocilium organization	1	842.6×	0.002	PDZD7
establishment of protein localization	1	432.1×	0.003	PDZD7
establishment of localization in cell	1	160.5×	0.007	PDZD7
sensory perception of sound	1	100.9×	0.010	PDZD7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDZD7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PDZD7

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PDZD7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.