RDX

protein-coding

radixin, the group of FERM domain containing

Gene summary

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]

Previous symbols:

DFNB24

MANE transcript

NM_002906.4

Inheritance

ClinVar variants

P:23U:111B:48

Top phenotype

Deafness, autosomal recessive 24

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr11:109,864,295-110,296,712

External References & Databases

Ensembl (ENSG00000137710)

Transcript & Mutation Effects

hg38 • Region Span ~432.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive nonsyndromic hearing loss 24STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012602

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive nonsyndromic hearing loss 24STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012602

Submitter: PanelApp Australia

autosomal recessive nonsyndromic hearing loss 24STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012602

Submitter: Ambry Genetics

nonsyndromic genetic hearing lossDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: ClinGen

The RDX gene has been associated with autosomal recessive nonsndromic hearing loss using the ClinGen Clinical Validity Framework as of 7/14/2017. This association was made using case-level data only. At least 7 missense, frameshift, nonsense, and splice-site variants have been reported in humans. RDX was first associated with this disease in humans as early as 2007 (Khan et al.). Association is seen in at least 6 probands in 4 publications (17226784, 19215054, 22567349, 26226137), as well as one unpublished case at the Laboratory for Molecular Medicine. Variants in this gene segregated with disease in 11 additional family members. This gene-disease association is supported by a null mouse model and relevant expression and protein interaction studies. In summary, RDX is definitively associated with autosomal recessive nonsyndromic hearing loss. This classification was approved by the ClinGen Hearing Loss Working Group on 1/2/2018.

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 24AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

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

Refs: 17226784; 19215054

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RDX variants in ClinVar

8 Conditions Cataloged

not providedTotal: 135

Inborn genetic diseasesTotal: 57

Autosomal recessive nonsyndromic hearing loss 24Total: 46

not specifiedTotal: 29

RDX-related disorderTotal: 9

Hearing impairmentTotal: 2

Nonsyndromic genetic hearing lossTotal: 1

Rare genetic deafnessTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002906.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	40 clinvar		46
missense	1 clinvar		104 clinvar	7 clinvar	1 clinvar	113
nonsense	3 clinvar	5 clinvar	1 clinvar			9
start loss						0
frameshift	8 clinvar	3 clinvar				11
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar				3
Total	13	10	111	47	1	182

Highest pathogenic variant AF is 0.00000868565

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002906.4	RefSeq	NP_002897.1	13	MANE Select
ENST00000645495.2	Ensembl	ENSP00000496503.2	13	MANE Select
NM_001260492.2	RefSeq	NP_001247421.1	14	Standard
NM_001260493.2	RefSeq	NP_001247422.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Proteoglycans in cancer - Homo sapiens (human)
MicroRNAs in cancer - Homo sapiens (human)
Regulation of Actin Cytoskeleton

Biological Process

regulation of cell shape
regulation of cell size
positive regulation of gene expression
protein kinase A signaling
microvillus assembly

Molecular Function

RNA binding
actin binding
protein binding
protein domain specific binding
protein homodimerization activity

Cellular Component

ruffle
extracellular space
plasma membrane
microvillus
cell-cell adherens junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000405097
Coding exons: 14
Length: 121843
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125748
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.908	275	321	0.857	0.0000173	4011
Missense (PolyPhen)		86	111.95	0.76821		1467
Synonymous	-0.387	111	106	1.05	0.00000557	1035
Loss of Function	4.82	8	41.5	0.193	0.00000246	467

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00022	0.00021	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane.;
Disease: DISEASE: Deafness, autosomal recessive, 24 (DFNB24) [MIM:611022]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:17226784}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.268

Intolerance Scores

LoFtool: 0.203
RVIS EVS: -0.56
RVIS percentile EVS: 19.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.903

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium