GeneBe

USH2A

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

Basic information

Region (hg38): 1:215622891-216423448

Previous symbols: [ "USH2" ]

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 5.

Transcript IDProtein IDCoding exonsMANE SelectMANE Plus Clinical
NM_206933.4NP_996816.371yes-
ENST00000307340.8ENSP00000305941.371yes-
NM_007123.6NP_009054.620--
ENST00000366942.3ENSP00000355909.320--

Phenotypes

GenCC

Source: genCC

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

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
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ClinVar

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

  • not_provided (7525 variants)
  • Usher_syndrome_type_2A (2655 variants)
  • Retinitis_pigmentosa_39 (1778 variants)
  • Retinal_dystrophy (827 variants)
  • not_specified (684 variants)
  • Inborn_genetic_diseases (606 variants)
  • Retinitis_pigmentosa (313 variants)
  • Usher_syndrome (272 variants)
  • USH2A-related_disorder (194 variants)
  • Rare_genetic_deafness (93 variants)
  • Usher_syndrome_type_2 (71 variants)
  • Hearing_impairment (23 variants)
  • Retinal_disorder (23 variants)
  • Monogenic_hearing_loss (20 variants)
  • Cone-rod_dystrophy (9 variants)
  • See_cases (8 variants)
  • Leber_congenital_amaurosis (8 variants)
  • Autosomal_recessive_USH2A-related_disorders (6 variants)
  • Ear_malformation (6 variants)
  • Autosomal_recessive_retinitis_pigmentosa (6 variants)
  • Congenital_sensorineural_hearing_impairment (4 variants)
  • Autosomal_dominant_nonsyndromic_hearing_loss_36 (4 variants)
  • Nonsyndromic_genetic_hearing_loss (3 variants)
  • Visual_impairment (3 variants)
  • Hypoplasia_of_the_brainstem (2 variants)
  • Motor_delay (2 variants)
  • Delayed_speech_and_language_development (2 variants)
  • Progressive_cone_dystrophy_(without_rod_involvement) (2 variants)
  • Usher_syndrome_type_1 (2 variants)
  • Congenital_stationary_night_blindness (2 variants)
  • Childhood_onset_hearing_loss (2 variants)
  • Cerebellar_hemisphere_hypoplasia (2 variants)
  • Cone-rod_dystrophy_3 (2 variants)
  • Amblyopia (2 variants)
  • Optic_atrophy (2 variants)
  • Retinal_degeneration (2 variants)
  • Joubert_syndrome (2 variants)
  • Congenital_cerebellar_hypoplasia (2 variants)
  • Retinal_pigment_epithelial_atrophy (1 variants)
  • Hearing_loss (1 variants)
  • Usher_syndrome_type_3A (1 variants)
  • Deafness (1 variants)
  • Rod-cone_dystrophy (1 variants)
  • Stargardt-like_macular_dystrophy (1 variants)
  • Pigmentary_retinopathy (1 variants)
  • Prostate_cancer (1 variants)
  • Hearing_loss,_autosomal_recessive (1 variants)
  • Macular_dystrophy (1 variants)
  • Blindness (1 variants)
  • Sensorineural_hearing_loss_disorder (1 variants)
  • Bardet-Biedl_syndrome (1 variants)
  • Abnormal_macular_morphology (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. These statistics are base on transcript: NM_206933.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
9
clinvar
76
clinvar
2380
clinvar
26
clinvar
 2494
missense
88
clinvar
406
clinvar
2819
clinvar
254
clinvar
27
clinvar
 3594
nonsense
346
clinvar
256
clinvar
5
clinvar
 607
start loss
1
1
frameshift
446
clinvar
399
clinvar
7
clinvar
 852
splice donor/acceptor (+/-2bp)
95
clinvar
215
clinvar
6
clinvar
1
clinvar
 317
Total 978 1286 2913 2635 53

Highest pathogenic variant AF is 0.0014603126

Loading clinvar variants...

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
12496217851257480.00313
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

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

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
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