USH2A Usher syndrome 2A (autosomal recessive, mild) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: USH2Aprovided by HGNC
Official Full Name: Usher syndrome 2A (autosomal recessive, mild)provided by HGNC
Primary source: HGNC:12601
See related: Ensembl:ENSG00000042781; HPRD:02042; HPRD:09759; MIM:608400; Vega:OTTHUMG00000037079
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: US2; RP39; USH2; dJ1111A8.1
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]

Genomic context

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Location :: 1q41

Sequence :: Chromosome: 1; NC_000001.10 (215796236..216596738, complement)

See USH2A in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

USH2A (c.2276 G>T) is the likely disease-causing gene in two non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa.
Title: Application of a high-throughput genotyping method for loci exclusion in non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa.
Touch sensitivity was impaired in a cohort of individuals carrying pathogenic mutations in the USH2A gene, but not in other cases of Usher syndrome.
Title: A genetic basis for mechanosensory traits in humans.
Mutation found in USH2A, GPR98, or DFNB31 account for the vast majority of USH2 patients and their analysis provide a robust pathway for routine molecular diagnosis.
Title: Non-USH2A mutations in USH2 patients.
Results establish the mutational frequencies for the short isoform of USH2A gene in Usher syndrome type II.
Title: [Mutational frequencies in usherin(USH2A gene) in 26 Colombian individuals with Usher syndrome type II].
USH2A sequencing in three affected members of a large family, referred for the recessive USH2 syndrome, identified a single pathogenic alteration in one of them and a different mutation in the two affected nieces.
Title: Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.
Mutations in USH2A are responsible for 76.1% of USH2 disease in patients of Spanish origin.
Title: Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations.
the mutation spectrum for USH2A among Japanese patients largely differs from Caucasian, Jewish and Palestinian patients.
Title: Novel USH2A mutations in Japanese Usher syndrome type 2 patients: marked differences in the mutation spectrum between the Japanese and other populations.
Seven novel mutations (two missense, one 7-bp deletion, two small deletions, and two nonsense) were detected in the four Chinese families after sequencing analysis of USH2A.
Title: Seven novel mutations in the long isoform of the USH2A gene in Chinese families with nonsyndromic retinitis pigmentosa and Usher syndrome Type II.
35 USH2A gene deleterious mutations in patients with USH2 were identified including 17 nonsense mutations, 9 frameshift mutations, 5 splice-site mutations, and 4 small in-frame deletions or insertions. Twenty-seven mutations were novel.
Title: Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa.
An exhaustive c.2299delG/control haplotype study suggests that the major source of variability in the USH2A gene is recombination.
Title: The USH2A c.2299delG mutation: dating its common origin in a Southern European population.

Submit: New GeneRIF Correction See all (39)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Retinitis pigmentosa (RP) is a group of inherited disorders in which abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium (RPE) of the retina lead to progressive visual loss. Affected individuals first experience defective dark adaptation or "night blindness," followed by constriction of peripheral visual fields and, eventually, loss of central vision late in the course of the disease.

Diagnosis Testing

The diagnosis of RP relies on documentation of progressive loss in photoreceptor function by electroretinography (ERG) and visual field testing. Mutations in more than 50 different genes or loci are known to cause nonsyndromic RP. Molecular genetic testing is available on a clinical basis for many RP- related genes. For all other genes, molecular genetic testing is available on a research basis only.

Genetic Counseling

The mode of inheritance of RP is determined by family history and, in some instances, by molecular genetic testing. RP can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Females with an X-linked RP mutation may be unaffected or may show clinical symptoms. Such affected females are usually (but not always) less severely affected than males of the same age. Some digenic and mitochondrial forms have also been described. Genetic counseling depends on an accurate diagnosis, determination of the mode of inheritance in each family, and results of molecular genetic testing.

References

PMID: 20301590

Usher syndrome, type 2A

MIM: 276901

Genetic Testing Registry

Summary from GeneReviews: Usher Syndrome Type II

Disease Characteristics

Usher syndrome type II is characterized by congenital (i.e., prelingual) bilateral sensorineural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies, intact vestibular responses, and retinitis pigmentosa (RP). RP is progressive, bilateral, symmetric retinal degeneration that begins with night blindness and constricted visual fields (tunnel vision) and eventually includes decreased central visual acuity; the rate and degree of vision loss vary within and among families.

Diagnosis Testing

The diagnosis of Usher syndrome type II is established on clinical grounds using electrophysiologic and subjective tests of hearing and retinal function. Three genes are known to be associated with Usher syndrome type II: USH2A (accounting for 80% of cases), GPR98 (VLGR1) (~15% of cases), and DFNB31 (<5% of cases). A fourth locus has been provisionally mapped to 15q. Molecular genetic testing for USH2A, GPR98, and DFNB31 is available clinically.

Genetic Counseling

Usher syndrome type II is inherited in an autosomal recessive manner. Each subsequent pregnancy of a couple who has had a child with Usher syndrome type II has a 25% chance of resulting in an affected child, a 50% chance of resulting in an unaffected child who is a carrier, and a 25% chance of resulting in an unaffected child who is not a carrier. Prenatal testing is possible for pregnancies at increased risk for USH2A if the disease-causing mutations have been identified in the family.

References

PMID: 20301515

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
O75445	Q01955	COL4A3	HPRD	PubMed
O75445	P05783	KRT18	HPRD	PubMed
BioGRID:113242	BioGRID:107140	BRCA1	BioGRID	PubMed	Two-hybrid

General gene information

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Markers

AL009851 (e-PCR)
- UniSTS:41728

SHGC-132295 (e-PCR)
- UniSTS:170766

G63076 (e-PCR)
- UniSTS:140051

G62491 (e-PCR)
- UniSTS:139549

SHGC-78958 (e-PCR)
- UniSTS:100906

D1S2827 (e-PCR), detects polymorphism
- UniSTS:50739

SHGC-155213 (e-PCR)
- UniSTS:182068

AL009345 (e-PCR)
- UniSTS:13111

SHGC-106817 (e-PCR)
- UniSTS:170049

AL033887 (e-PCR)
- UniSTS:93763

AL010107 (e-PCR)
- UniSTS:9033

SHGC-84884 (e-PCR)
- UniSTS:104780

AL034204 (e-PCR)
- UniSTS:94030

D1S2171 (e-PCR)
- UniSTS:50772

AFM248tc1 (e-PCR)
- UniSTS:36951

AL009491 (e-PCR)
- UniSTS:61537

RH79627 (e-PCR)
- UniSTS:90212

RH118881 (e-PCR)
- UniSTS:138861

D1S2435 (e-PCR)
- UniSTS:67214

SHGC-111484 (e-PCR)
- UniSTS:181917

AL009855 (e-PCR)
- UniSTS:23467

AL009286 (e-PCR)
- UniSTS:32686

AL033963 (e-PCR)
- UniSTS:93375

D1S2086 (e-PCR)
- UniSTS:35009

AL034147 (e-PCR)
- UniSTS:93917

SHGC-76355 (e-PCR)
- UniSTS:78303

143XF10 (e-PCR)
- UniSTS:6625

RH119862 (e-PCR)
- UniSTS:133607

SHGC-144902 (e-PCR)
- UniSTS:174316

AFM268zd1 (e-PCR)
- UniSTS:52214

Genotypes

See USH2A SNP Geneview Report
See USH2A SNP Genotype Report
See USH2A SNP Variation Viewer Report

Homology

Homologs of the USH2A gene: The USH2A gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
collagen binding	IDA Inferred from Direct Assay more info	PubMed
myosin binding	ISS Inferred from Sequence or Structural Similarity more info
protein binding	IPI Inferred from Physical Interaction more info

Process	Evidence Code	Pubs
hair cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
inner ear receptor cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
maintenance of organ identity	IMP Inferred from Mutant Phenotype more info	PubMed
photoreceptor cell maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
response to stimulus	IEA Inferred from Electronic Annotation more info
sensory perception of light stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
sensory perception of sound	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
basement membrane	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
integral to membrane	IEA Inferred from Electronic Annotation more info
stereocilia ankle link complex	ISS Inferred from Sequence or Structural Similarity more info
stereocilium bundle	ISS Inferred from Sequence or Structural Similarity more info
stereocilium membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: usherin

Names: usherin; usher syndrome type-2A protein; usher syndrome type IIa protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009497.1 RefSeqGene

Range

5001..805503

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_007123.5 → NP_009054.5 usherin isoform A

Status: REVIEWED

Description

Transcript Variant: This variant (1) uses a different splice site in its 3' coding region when compared to variant 2. The resulting protein (isoform A) has a shorter and distinct C-terminus, compared to isoform B.

Source sequence(s)

AF055580, AY481573

Consensus CDS

CCDS1516.1

UniProtKB/Swiss-Prot

O75445

Related

ENSP00000355909, OTTHUMP00000035145, ENST00000366942, OTTHUMT00000090016

Conserved Domains (6) summary

cd00055
Location:900 – 948
Blast Score: 134

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00063
Location:1243 – 1357
Blast Score: 147

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

smart00560
Location:146 – 283
Blast Score: 351

LamGL; LamG-like jellyroll fold domain

smart00180
Location:900 – 944
Blast Score: 143

EGF_Lam; Laminin-type epidermal growth factor-like domai

pfam00053
Location:747 – 795
Blast Score: 142

Laminin_EGF; Laminin EGF-like (Domains III and V)

cl02806
Location:313 – 516
Blast Score: 227

Laminin_N; Laminin N-terminal (Domain VI)
NM_206933.2 → NP_996816.2 usherin isoform B

Status: REVIEWED

Description

Transcript Variant: This variant (2) is the longer transcript and it encodes the longer isoform (B).

Source sequence(s)

AA883599, AADB02001158, AF055580, AY481573

Consensus CDS

CCDS31025.1

UniProtKB/Swiss-Prot

O75445

Related

ENSP00000305941, OTTHUMP00000063383, ENST00000307340, OTTHUMT00000128138

Conserved Domains (8) summary

cd00055
Location:900 – 948
Blast Score: 157

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00063
Location:2533 – 2619
Blast Score: 141

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00110
Location:1716 – 1868
Blast Score: 247

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

smart00560
Location:146 – 283
Blast Score: 333

LamGL; LamG-like jellyroll fold domain

smart00060
Location:3445 – 3485
Blast Score: 89

FN3; Fibronectin type 3 domain

smart00180
Location:900 – 948
Blast Score: 167

EGF_Lam; Laminin-type epidermal growth factor-like domai

pfam00053
Location:641 – 691
Blast Score: 163

Laminin_EGF; Laminin EGF-like (Domains III and V)

cl02806
Location:313 – 516
Blast Score: 232

Laminin_N; Laminin N-terminal (Domain VI)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p10 Primary Assembly

Range

215796236..216596738, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

186470498..187272188, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018912.1 Alternate CHM1_1.0

Range

222591203..223391733, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AADB02001158.1	None
genomic	ABBA01048123.1 (79565..302200)	None
genomic	ABBA01048124.1	None
genomic	ABBA01048125.1	None
genomic	ABBA01048126.1	None
genomic	ABBA01048127.1	None
genomic	ABBA01048128.1	None
genomic	ABBA01048129.1	None
genomic	ABBA01048130.1	None
genomic	AC092799.2 (2006..142945)	None
genomic	AC093581.2 (2001..156992)	None
genomic	AC119429.3 (2475..15468)	None
genomic	AC138024.2	None
genomic	AF091889.1	AAF75819.1
genomic	AL139259.15 (2001..28489)	None
genomic	AL358452.3	None
genomic	AL358858.19 (101..93856)	None
genomic	AL445650.9 (101..61103)	None
genomic	AL513305.10	None
genomic	AMYH01001727.1 (181633..330335)	None
genomic	AMYH01001728.1	None
genomic	AMYH01001729.1	None
mRNA	AA883599.1	None
mRNA	AF055580.2	AAC23748.2
mRNA	AY481573.1	AAS47698.1