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GeneBe

USH2A

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

Basic information

Region (hg38): 1:215622890-216423448

Previous symbols: [ "USH2" ]

Links

ENSG00000042781 ∙ NCBI:7399 ∙ OMIM:608400 ∙ HGNC:12601 ∙ Uniprot:O75445 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Usher syndrome type 2A (Strong), mode of inheritance: AR
  • retinitis pigmentosa (Supportive), mode of inheritance: AD
  • Usher syndrome type 2 (Supportive), mode of inheritance: AR
  • Usher syndrome type 2A (Definitive), mode of inheritance: AR
  • retinitis pigmentosa 39 (Strong), mode of inheritance: AR
  • Usher syndrome type 2A (Strong), mode of inheritance: AR
  • Usher syndrome type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Usher syndrome, type 2AARAudiologic/OtolaryngologicEarly 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)Audiologic/Otolaryngologic; Ophthalmologic1580321; 9624053; 10775529; 10729113; 12427073; 15015129; 16301217; 16098008; 15671307; 17085681; 17296898; 18273898; 19881469; 20440071; 20301515

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USH2A gene.

  • not provided (6395 variants)
  • Usher syndrome type 2A (1735 variants)
  • Retinitis pigmentosa 39 (1413 variants)
  • not specified (629 variants)
  • Retinal dystrophy (369 variants)
  • Retinitis pigmentosa 39;Usher syndrome type 2A (305 variants)
  • Retinitis pigmentosa (301 variants)
  • Usher syndrome type 2A;Retinitis pigmentosa 39 (272 variants)
  • Usher syndrome (184 variants)
  • Inborn genetic diseases (178 variants)
  • Rare genetic deafness (85 variants)
  • Usher syndrome type 2 (56 variants)
  • USH2A-related condition (25 variants)
  • Hearing impairment (18 variants)
  • USH2A-Related Disorders (15 variants)
  • Leber congenital amaurosis (8 variants)
  • Retinitis pigmentosa-deafness syndrome (7 variants)
  • Retinitis Pigmentosa, Recessive (7 variants)
  • Cone-rod dystrophy (7 variants)
  • Ear malformation (6 variants)
  • - (4 variants)
  • See cases (3 variants)
  • Rare genetic deafness;Usher syndrome (3 variants)
  • Usher syndrome;Rare genetic deafness (3 variants)
  • Autosomal recessive retinitis pigmentosa (3 variants)
  • Nonsyndromic genetic hearing loss (3 variants)
  • Congenital sensorineural hearing impairment (2 variants)
  • Childhood onset hearing loss (2 variants)
  • Rod-cone dystrophy (2 variants)
  • 8 conditions (2 variants)
  • Progressive cone dystrophy (without rod involvement) (2 variants)
  • Congenital stationary night blindness (2 variants)
  • 13 conditions (2 variants)
  • Cone-rod dystrophy 3 (2 variants)
  • Usher syndrome type 1 (2 variants)
  • Retinal degeneration;Retinal dystrophy (1 variants)
  • Hearing loss, autosomal recessive (1 variants)
  • Bardet-Biedl syndrome (1 variants)
  • Sensorineural hearing loss disorder (1 variants)
  • Retinal dystrophy;Retinal degeneration (1 variants)
  • Usher syndrome type 3A (1 variants)
  • Pigmentary retinopathy (1 variants)
  • Surfactant metabolism dysfunction, pulmonary, 2 (1 variants)
  • Deafness (1 variants)
  • Pigmentary retinopathy;Retinal pigment epithelial atrophy;Blindness;Abnormal macular morphology;Rod-cone dystrophy (1 variants)
  • Macular dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USH2A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
15
clinvar
1865
clinvar
34
clinvar
 1915
missense
70
clinvar
138
clinvar
2004
clinvar
98
clinvar
36
clinvar
 2346
nonsense
290
clinvar
174
clinvar
1
clinvar
 465
start loss
1
clinvar
 1
frameshift
345
clinvar
247
clinvar
6
clinvar
 598
inframe indel
5
clinvar
6
clinvar
45
clinvar
 56
splice donor/acceptor (+/-2bp)
64
clinvar
157
clinvar
2
clinvar
 223
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
4
6
85
201
15
 311
non coding
?
    UTR, intron and other, non coding variants
1
clinvar
6
clinvar
61
clinvar
543
clinvar
223
clinvar
 834
Total 776 728 2135 2506 293

Highest pathogenic variant AF is 0.00131

Variants in USH2A

This is a list of pathogenic ClinVar variants found in the USH2A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-215625538-C-A Benign (Jan 25, 2019)1297792
1-215625732-T-G Benign (Mar 03, 2015)1227419
1-215625777-T-C not specified • Retinitis pigmentosa 39 • Usher syndrome type 2A Benign/Likely benign (Apr 11, 2023)166410
1-215625784-C-A Likely benign (Mar 27, 2022)2070888
1-215625784-C-G Likely benign (Oct 19, 2023)1090538
1-215625786-G-A Likely benign (Apr 16, 2022)1911438
1-215625787-G-A Likely benign (Dec 25, 2021)1103234
1-215625789-G-T Uncertain significance (Jan 19, 2020)1051232
1-215625790-G-A Likely benign (Jun 14, 2022)1136107
1-215625791-G-T Uncertain significance (Sep 27, 2022)1361979
1-215625793-G-A Likely benign (Mar 14, 2022)1081267
1-215625802-T-C Likely benign (Jun 24, 2023)2727099
1-215625806-G-C Uncertain significance (Aug 22, 2022)1350571
1-215625807-T-C Inborn genetic diseases Uncertain significance (Feb 07, 2023)2482240
1-215625808-G-A Usher syndrome type 2A Likely benign (Oct 25, 2023)1011559
1-215625809-C-A not specified Uncertain significance (Sep 28, 2016)440394
1-215625809-C-T not specified • Usher syndrome type 2A;Retinitis pigmentosa 39 Conflicting classifications of pathogenicity (Apr 01, 2023)179824
1-215625810-G-A Usher syndrome type 2A • Retinitis pigmentosa 39 Uncertain significance (Nov 04, 2023)1217401
1-215625810-GTTCC-G Uncertain significance (Jun 19, 2022)2419696
1-215625812-TC-T Retinitis pigmentosa 39;Usher syndrome type 2A • Usher syndrome type 2A • Retinitis pigmentosa 39 Uncertain significance (Nov 04, 2023)553718
1-215625813-C-A Retinitis pigmentosa 39;Usher syndrome type 2A Uncertain significance (Sep 11, 2017)553657
1-215625815-T-A Usher syndrome type 2A • Retinitis pigmentosa 39 Uncertain significance (Nov 04, 2023)1358771
1-215625816-T-C Retinitis pigmentosa 39 Uncertain significance (-)2584892
1-215625823-T-C Likely benign (Aug 01, 2019)1103123
1-215625826-G-A Likely benign (Jul 24, 2023)1127371

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
USH2Aprotein_codingprotein_codingENST00000307340 71800503
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.57e-940.000051212496217851257480.00313
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-2.4730762.71e+31.130.00014733915
Missense in Polyphen902832.761.083110397
Synonymous-4.0011741.01e+31.160.000058410217
Loss of Function3.461782350.7560.00001202941

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.006720.00660
Ashkenazi Jewish0.001190.00119
East Asian0.003100.00299
Finnish0.001480.00148
European (Non-Finnish)0.003240.00323
Middle Eastern0.003100.00299
South Asian0.003990.00393
Other0.004740.00473

dbNSFP

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

Haploinsufficiency Scores

pHI
0.158
hipred
Y
hipred_score
0.543
ghis

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.0777

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Ush2a
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype;

Zebrafish Information Network

Gene name
ush2a
Affected structure
eye photoreceptor cell
Phenotype tag
abnormal
Phenotype quality
apoptotic

Gene ontology

Biological process
visual perception;sensory perception of sound;hair cell differentiation;establishment of protein localization;photoreceptor cell maintenance;maintenance of animal organ identity;response to stimulus;sensory perception of light stimulus;inner ear receptor cell differentiation
Cellular component
photoreceptor inner segment;stereocilia ankle link;stereocilia ankle link complex;basement membrane;cytoplasm;integral component of membrane;apical plasma membrane;photoreceptor connecting cilium;stereocilium bundle;ciliary basal body;neuronal cell body;terminal bouton;stereocilium membrane;periciliary membrane compartment;USH2 complex
Molecular function
protein binding;collagen binding;myosin binding;protein homodimerization activity