RDX

Chr 11AR

radixin

Also known as: DFNB24

NCBI Gene: 5962 ENSG00000137710 UniProt: P35241 OMIM: 179410

Radixin is a cytoskeletal protein that binds the barbed end of actin filaments to the plasma membrane, linking the actin cytoskeleton to the cell membrane. Mutations cause autosomal recessive deafness (DFNB24). The gene is highly constrained against loss-of-function variants, suggesting that complete loss of radixin function is likely pathogenic.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. It is highly similar in sequence to both ezrin and moesin. The radixin gene has been localized by fluorescence in situ hybridization to 11q23. A truncated version representing a pseudogene (RDXP2) was assigned to Xp21.3. Another pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by Southern and PCR analyses. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 24MIM #611022

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nonsyndromic genetic hearing loss · AR · ClinGen 2018

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

159

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.35

LOEUF· LoF intol.

—

Mechanism

📖

GeneReview available — RDX

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.852

Z-score 4.82

OE 0.19 (0.11–0.35)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.91Z-score

OE missense 0.86 (0.78–0.95)

275 obs / 320.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.11–0.35)

0≤0.351.4

Missense OE?0.86 (0.78–0.95)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 8 / 41.5Missense obs/exp: 275 / 320.8Syn Z: -0.39

Background carrier burden — how many people carry a rare variant somewhere in RDX?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

679 rare PASS variants

Rare truncating (LoF)

1 in 1,800

99 rare PASS variants

Rare synonymous (reference)

1 in 150

235 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RDX. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 1,600
South Asian	~43k	1 in 62	1 in 4,300
Remaining (unassigned)	~30k	1 in 110	1 in 2,400
European (Finnish)	~27k	1 in 760	1 in 3,700
Admixed American	~22k	1 in 74	1 in 3,200
African / African American	~21k	1 in 72	1 in 1,400
East Asian	~20k	1 in 140	1 in 1,900
Ashkenazi Jewish	~13k	1 in 310	1 in 1,300
Middle Eastern	~2,884	1 in 85	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 13 coding exons well covered in gnomAD exomes; exons 2, 8 marginal. Genomes: all 13.? see exons ↓