GeneBe

USH2A

protein-coding

usherin, the group of USH2 complex |Fibronectin type III domain containing

Gene summary

This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Previous symbols:
  • USH2

MANE transcript

NM_206933.4

Inheritance

AR, AD

ClinVar variants

P:2269U:2929B:2690

Top phenotype

Usher syndrome, type 2A

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr1:215,622,891-216,423,448

External References & Databases

Ensembl (ENSG00000042781)NCBI Gene (7399)OMIM (608400)HGNC:12601GenCCUniProt (O75445)AlphaFoldClinVar (USH2A)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~800.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Usher syndrome type 2ADEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010169

Submitter: Natera

Usher syndrome type 2ADEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010169

Submitter: G2P

Usher syndrome type 2ASTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010169

Submitter: PanelApp Australia

Usher syndrome type 2ASTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010169

Submitter: Labcorp Genetics (formerly Invitae)

retinitis pigmentosa 39STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013436

Submitter: PanelApp Australia

retinitis pigmentosaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Orphanet

Usher syndrome type 2DEFINITIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0016484

Submitter: ClinGen

Usher syndrome type 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016484

Submitter: Orphanet

retinitis pigmentosa 39STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013436

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Usher syndrome, type 2AAR

Manifestation: Audiologic/Otolaryngologic; Ophthalmologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial)

Refs: 1580321; 9624053; 10775529; 10729113; 12427073; 15015129; 16301217; 16098008; 15671307; 17085681; 17296898; 18273898; 19881469; 20440071; 20301515Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to USH2A variants in ClinVar

54 Conditions Cataloged
not providedTotal: 7531
Usher syndrome type 2ATotal: 2671
Retinitis pigmentosa 39Total: 1786
Retinal dystrophyTotal: 819
not specifiedTotal: 698
Inborn genetic diseasesTotal: 622
Retinitis pigmentosaTotal: 313
Usher syndromeTotal: 277

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_206933.4. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
8
clinvar
76
clinvar
2381
clinvar
26
clinvar
 2494
missense
90
clinvar
404
clinvar
2835
clinvar
257
clinvar
25
clinvar
 3611
nonsense
346
clinvar
258
clinvar
5
clinvar
 609
start loss
1
clinvar
 1
frameshift
447
clinvar
402
clinvar
7
clinvar
 856
splice donor/acceptor (+/-2bp)
95
clinvar
215
clinvar
6
clinvar
1
clinvar
 317
Total981128829292639517888

Highest pathogenic variant AF is 0.0014603126

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_206933.4RefSeqNP_996816.371MANE Select
ENST00000307340.8EnsemblENSP00000305941.371MANE Select
NM_007123.6RefSeqNP_009054.620Standard
ENST00000366942.3EnsemblENSP00000355909.320Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
ush2aDanio rerio

Structure: eye photoreceptor cell

Quality: apoptotic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • visual perception
  • sensory perception of sound
  • hair cell differentiation
  • establishment of protein localization
  • photoreceptor cell maintenance

Molecular Function

  • protein binding
  • collagen binding
  • myosin binding
  • protein homodimerization activity

Cellular Component

  • photoreceptor inner segment
  • stereocilia ankle link
  • stereocilia ankle link complex
  • basement membrane
  • cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000307340
Coding exons
71
Length
800503
Individuals with no LoFs
124962
Homozygous LoFs
1
Heterozygous LoFs
785
Defined
125748
p
0.00313
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-2.4730762.71e+31.130.00014733915
Missense (PolyPhen)902832.761.083110397
Synonymous-4.0011741.01e+31.160.000058410217
Loss of Function3.461782350.7560.00001202941

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00300.0029notable
Latino/Admixed American0.00370.0036notable
Ashkenazi Jewish0.00120.0012notable
East Asian0.00310.0030notable
Finnish0.00150.0015notable
European (Non-Finnish)0.00320.0032notable
South Asian0.00400.0039notable
Other0.00470.0047notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in hearing and vision.;
Disease
DISEASE: Usher syndrome 2A (USH2A) [MIM:276901]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. {ECO:0000269|PubMed:10729113, ECO:0000269|PubMed:10738000, ECO:0000269|PubMed:10909849, ECO:0000269|PubMed:11311042, ECO:0000269|PubMed:12112664, ECO:0000269|PubMed:12525556, ECO:0000269|PubMed:14970843, ECO:0000269|PubMed:15015129, ECO:0000269|PubMed:15025721, ECO:0000269|PubMed:15241801, ECO:0000269|PubMed:15325563, ECO:0000269|PubMed:17085681, ECO:0000269|PubMed:17405132, ECO:0000269|PubMed:18273898, ECO:0000269|PubMed:18452394, ECO:0000269|PubMed:19683999, ECO:0000269|PubMed:19737284, ECO:0000269|PubMed:20309401, ECO:0000269|PubMed:20440071, ECO:0000269|PubMed:20507924, ECO:0000269|PubMed:21593743, ECO:0000269|PubMed:21686329, ECO:0000269|PubMed:22004887, ECO:0000269|PubMed:23737954, ECO:0000269|PubMed:26377068, ECO:0000269|PubMed:9624053}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 39 (RP39) [MIM:613809]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:10775529, ECO:0000269|PubMed:12112664, ECO:0000269|PubMed:12427073, ECO:0000269|PubMed:15325563, ECO:0000269|PubMed:16098008, ECO:0000269|PubMed:17296898, ECO:0000269|PubMed:20507924, ECO:0000269|PubMed:21686329, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:24227914}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in USH2A has been found in a patient with a form of non-syndromic sensorineural hearing loss. {ECO:0000269|PubMed:25388789}.;

Intolerance Scores

LoFtool
0.924
RVIS EVS
4.18
RVIS percentile EVS
99.71

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.0777

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh
Feedback | API | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.