Autosomal recessive nonsyndromic hearing loss 24

Summary

Autosomal recessive nonsyndromic hearing loss 24 (MONDO:0012602) is a disease caused by RDX (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RDX (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 102

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 24
Mondo ID	MONDO:0012602
MeSH	C567027
OMIM	611022
DOID	DOID:0110482
UMLS	C1970239
MedGen	370208
GARD	0022626
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 24 · autosomal recessive nonsyndromic deafness 24 · autosomal recessive nonsyndromic deafness caused by mutation in RDX · autosomal recessive nonsyndromic deafness type 24 · autosomal recessive nonsyndromic hearing loss 24 · deafness, autosomal recessive 24 · deafness, autosomal recessive type 24 · DFNB24 · RDX autosomal recessive nonsyndromic deafness

Data availability: 102 ClinVar variants · 3 GenCC gene-disease records.

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 › autosomal recessive nonsyndromic hearing loss 24

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 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 57, 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

102 retrieved; paginated sample, class counts are floors:

75 uncertain significance, 8 pathogenic, 7 likely pathogenic, 6 conflicting classifications of pathogenicity, 3 likely benign, 2 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13184	NM_002906.4(RDX):c.1732G>A (p.Asp578Asn)	RDX	Pathogenic	no assertion criteria provided
13185	NM_002906.4(RDX):c.1405dup (p.Ala469fs)	RDX	Pathogenic	no assertion criteria provided
13186	NM_002906.4(RDX):c.463C>T (p.Gln155Ter)	RDX	Pathogenic	no assertion criteria provided
1698704	NM_002906.4(RDX):c.1346del (p.Ala449fs)	RDX	Pathogenic	criteria provided, single submitter
179207	NM_002906.4(RDX):c.1308del (p.Lys438fs)	RDX	Pathogenic	criteria provided, multiple submitters, no conflicts
2585105	NM_002906.4(RDX):c.1076_1079del (p.Ile359fs)	RDX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
638047	NM_002906.4(RDX):c.551+2T>C	RDX	Pathogenic	criteria provided, single submitter
982441	NM_002906.4(RDX):c.1108C>T (p.Arg370Ter)	RDX	Pathogenic	criteria provided, single submitter
983525	NM_002906.4(RDX):c.129G>A (p.Trp43Ter)	RDX	Pathogenic	criteria provided, single submitter
13187	NM_002906.4(RDX):c.698+1G>A	RDX	Likely pathogenic	criteria provided, single submitter
1325000	NM_002906.4(RDX):c.1141C>T (p.Arg381Ter)	RDX	Likely pathogenic	criteria provided, single submitter
1333282	NM_002906.4(RDX):c.1135C>T (p.Arg379Ter)	RDX	Likely pathogenic	criteria provided, single submitter
1334117	NM_002906.4(RDX):c.513_514del (p.Arg171fs)	RDX	Likely pathogenic	criteria provided, single submitter
3061950	NM_002906.4(RDX):c.295C>T (p.Gln99Ter)	RDX	Likely pathogenic	criteria provided, single submitter
4845838	NM_002906.4(RDX):c.1412dup (p.Pro472fs)	RDX	Likely pathogenic	criteria provided, single submitter
983524	NM_002906.4(RDX):c.-64-1215_12+348del	RDX	Likely pathogenic	criteria provided, single submitter
165054	NM_002906.4(RDX):c.354G>T (p.Pro118=)	RDX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
302342	NM_002906.4(RDX):c.1530C>T (p.Ser510=)	RDX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44636	NM_002906.4(RDX):c.1059A>G (p.Gln353=)	RDX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44638	NM_002906.4(RDX):c.1487C>T (p.Ala496Val)	RDX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
501592	NM_002906.4(RDX):c.1345-7T>C	RDX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
877232	NM_002906.4(RDX):c.6G>A (p.Pro2=)	RDX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2428636	NM_002906.4(RDX):c.1501T>C (p.Ser501Pro)	RDX	Uncertain significance	criteria provided, multiple submitters, no conflicts
302300	NM_002906.4(RDX):c.*2423C>T	RDX	Uncertain significance	criteria provided, single submitter
302301	NM_002906.4(RDX):c.*2057T>C	RDX	Uncertain significance	criteria provided, single submitter
302302	NM_002906.4(RDX):c.*2006A>G	RDX	Uncertain significance	criteria provided, multiple submitters, no conflicts
302303	NM_002906.4(RDX):c.*1961G>A	RDX	Uncertain significance	criteria provided, single submitter
302304	NM_002906.4(RDX):c.*1955A>G	RDX	Uncertain significance	criteria provided, single submitter
302305	NM_002906.4(RDX):c.*1579A>G	RDX	Uncertain significance	criteria provided, single submitter
302306	NM_002906.4(RDX):c.*1368A>C	RDX	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
RDX	Definitive	Autosomal recessive	nonsyndromic genetic hearing loss	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RDX	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
RDX	HGNC:9944	ENSG00000137710	P35241	Radixin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RDX	Radixin	Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RDX	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, Moesin_tail_sf

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
adrenal tissue	1
right adrenal gland cortex	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RDX	295	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RDX	3,167

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RDX	P35241	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Recycling pathway of L1	1	223.9×	0.006	RDX
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.006	RDX
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.006	RDX

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
regulation of adherens junction organization	1	16852.0×	0.001	RDX
regulation of postsynaptic neurotransmitter receptor diffusion trapping	1	5617.3×	0.001	RDX
regulation of Rap protein signal transduction	1	4213.0×	0.001	RDX
establishment of protein localization to plasma membrane	1	3370.4×	0.001	RDX
regulation of organelle assembly	1	3370.4×	0.001	RDX
microvillus assembly	1	1872.4×	0.001	RDX
positive regulation of early endosome to late endosome transport	1	1872.4×	0.001	RDX
positive regulation of protein localization to early endosome	1	1685.2×	0.001	RDX
cellular response to thyroid hormone stimulus	1	1532.0×	0.001	RDX
obsolete protein kinase A signaling	1	1404.3×	0.001	RDX
apical protein localization	1	991.3×	0.002	RDX
barbed-end actin filament capping	1	802.5×	0.002	RDX
establishment of endothelial barrier	1	766.0×	0.002	RDX
cellular response to platelet-derived growth factor stimulus	1	648.1×	0.002	RDX
positive regulation of G1/S transition of mitotic cell cycle	1	401.2×	0.003	RDX
positive regulation of protein catabolic process	1	203.0×	0.006	RDX
regulation of cell shape	1	123.0×	0.009	RDX
protein localization to plasma membrane	1	108.7×	0.010	RDX
positive regulation of gene expression	1	38.7×	0.026	RDX

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RDX	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RDX	1	Binding:1

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	RDX

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)
RDX	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.