USH1C USH1 protein network component harmonin [Homo sapiens (human)] - Gene

Summary

Official Symbol: USH1Cprovided by HGNC
Official Full Name: USH1 protein network component harmoninprovided by HGNC
Primary source: HGNC:HGNC:12597
See related: Ensembl:ENSG00000006611 MIM:605242; AllianceGenome:HGNC:12597
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: PDZ73; AIE-75; DFNB18; PDZ-45; PDZ-73; PDZD7C; DFNB18A; NY-CO-37; NY-CO-38; ush1cpst; PDZ-73/NY-CO-38
Summary: This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
Expression: Biased expression in small intestine (RPKM 13.7), duodenum (RPKM 13.0) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.1

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (17493900..17544416, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (17591495..17642149, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (17515447..17565963, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Expression and subcellular localization of USH1C/harmonin in human retina provides insights into pathomechanisms and therapy.
Title: Expression and subcellular localization of USH1C/harmonin in human retina provides insights into pathomechanisms and therapy.
Identification and computational analysis of USH1C, and SLC26A4 variants in Pakistani families with prelingual hearing loss.
Title: Identification and computational analysis of USH1C, and SLC26A4 variants in Pakistani families with prelingual hearing loss.
Myosin VII, USH1C, and ANKS4B or USH1G Together Form Condensed Molecular Assembly via Liquid-Liquid Phase Separation.
Title: Myosin VII, USH1C, and ANKS4B or USH1G Together Form Condensed Molecular Assembly via Liquid-Liquid Phase Separation.
Crystall structure shows the interactions between harmonin protein domains and its partner Myo7a.
Title: Myosin 7 and its adaptors link cadherins to actin.
The structure of the Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness-causing mutations in Myo7a CMF. Taken together, these findings suggest that binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common property of CMFs of Myo7a, Myo7b, and Myo15a.
Title: Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins.
We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease.
Title: Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving early molecular diagnosis.
Harmonin can adopt two different structural states, 'open' and 'closed', as a result of the self-interaction between its domains.
Title: Conformational switch of harmonin, a submembrane scaffold protein of the hair cell mechanoelectrical transduction machinery.
In summary, our studies provide novel insight into the functional relationship between USH1 and USH2 proteins in the cochlea and the retina as well as the disease mechanisms underlying USH1 and USH2.
Title: The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells.
ANKS4B, and MYO7B form a stable ternary complex for anchoring microvilli tip-link cadherins
Title: Mechanistic Basis of Organization of the Harmonin/USH1C-Mediated Brush Border Microvilli Tip-Link Complex.
harmonin and villin autoantibodies are sensitive and specific markers of IPEX, differentiate IPEX, including atypical cases, from other early childhood disorders associated with enteropathy
Title: Autoantibodies to harmonin and villin are diagnostic markers in children with IPEX syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (30)

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

Associated conditions

Description	Tests
Autosomal recessive nonsyndromic hearing loss 18A MedGen: C1865870 OMIM: 602092 GeneReviews: Genetic Hearing Loss Overview	not available
Usher syndrome type 1 MedGen: C1568247 OMIM: 276900 GeneReviews: Usher Syndrome Type I	not available
Usher syndrome type 1C MedGen: C1848604 OMIM: 276904 GeneReviews: Usher Syndrome Type I	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G59975 (e-PCR)
- UniSTS:137111

G54591 (e-PCR)
- UniSTS:117728

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables spectrin binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in G2/M transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in actin filament bundle assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in auditory receptor cell morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in brush border assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in brush border assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in brush border assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in equilibrioception	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in inner ear auditory receptor cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in inner ear morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in inner ear receptor cell stereocilium organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in inner ear receptor cell stereocilium organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in parallel actin filament bundle assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in photoreceptor cell maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to microvillus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to microvillus	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein-containing complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of microvillus length	ISS Inferred from Sequence or Structural Similarity more info
involved_in retinal cone cell development	IBA Inferred from Biological aspect of Ancestor more info
involved_in sensory perception of light stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sensory perception of sound	IBA Inferred from Biological aspect of Ancestor more info
involved_in sensory perception of sound	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in apical part of cell	IDA Inferred from Direct Assay more info	PubMed
located_in brush border	IDA Inferred from Direct Assay more info	PubMed
is_active_in cilium	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in microvillus	IDA Inferred from Direct Assay more info	PubMed
is_active_in photoreceptor inner segment	IBA Inferred from Biological aspect of Ancestor more info
located_in photoreceptor inner segment	ISS Inferred from Sequence or Structural Similarity more info
located_in photoreceptor outer segment	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
part_of stereocilia ankle link complex	IBA Inferred from Biological aspect of Ancestor more info
located_in stereocilium	ISS Inferred from Sequence or Structural Similarity more info
located_in stereocilium	TAS Traceable Author Statement more info	PubMed
is_active_in stereocilium tip	IBA Inferred from Biological aspect of Ancestor more info
located_in synapse	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: harmonin

Names: Usher syndrome 1C (autosomal recessive, severe); antigen NY-CO-38/NY-CO-37; autoimmune enteropathy-related antigen AIE-75; renal carcinoma antigen NY-REN-3; usher syndrome type-1C 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_011883.2 RefSeqGene

Range

5001..55517

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001297764.2 → NP_001284693.1 harmonin isoform c

See identical proteins and their annotated locations for NP_001284693.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has multiple differences in the coding region, compared to variant b3, one of which results in a translational frameshift. The resulting protein (isoform c) has a distinct C-terminus and is shorter than isoform b3.

Source sequence(s)

AB018687, AF039699, AK225614, BC016057

Consensus CDS

CCDS73265.1

UniProtKB/TrEMBL

A0A0S2Z4V1, B4DV53

Related

ENSP00000436934.1, ENST00000527020.5

Conserved Domains (4) summary

cd00992
Location:85 → 165

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd07353
Location:2 → 80

harmonin_N; N-terminal protein-binding module of harmonin

TIGR02794
Location:283 → 364

tolA_full; TolA protein

pfam03879
Location:297 → 339

Cgr1; Cgr1 family
NM_005709.4 → NP_005700.2 harmonin isoform a

See identical proteins and their annotated locations for NP_005700.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) has multiple differences in the coding region, compared to variant b3, one of which results in a translational frameshift. The resulting protein (isoform a) has a distinct C-terminus and is shorter than isoform b3.

Source sequence(s)

AC124799, KF455327

Consensus CDS

CCDS31438.1

UniProtKB/Swiss-Prot

A8K423, Q7RTU8, Q96B29, Q9UM04, Q9UM17, Q9UPC3, Q9Y6N9

UniProtKB/TrEMBL

A0A0S2Z4U9, B4DV53

Related

ENSP00000317018.4, ENST00000318024.9

Conserved Domains (4) summary

cd00992
Location:85 → 165

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd07353
Location:2 → 80

harmonin_N; N-terminal protein-binding module of harmonin

TIGR02794
Location:302 → 383

tolA_full; TolA protein

pfam03879
Location:316 → 358

Cgr1; Cgr1 family
NM_153676.4 → NP_710142.1 harmonin isoform b3

See identical proteins and their annotated locations for NP_710142.1

Status: REVIEWED

Description

Transcript Variant: This variant (b3) encodes the longest isoform (b3).

Source sequence(s)

AC124799, KF455327

Consensus CDS

CCDS7825.1

UniProtKB/Swiss-Prot

Q9Y6N9

Related

ENSP00000005226.7, ENST00000005226.12

Conserved Domains (4) summary

cd00992
Location:85 → 165

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd07353
Location:2 → 80

harmonin_N; N-terminal protein-binding module of harmonin

TIGR02794
Location:302 → 383

tolA_full; TolA protein

pfam03879
Location:316 → 358

Cgr1; Cgr1 family

RNA

NR_123738.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) has multiple differences compared to variant b3. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AB018687, AC124799, AF039699, AK225614

Related

ENST00000526313.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

17493900..17544416 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011519832.4 → XP_011518134.1 harmonin isoform X3

UniProtKB/TrEMBL

B4DV53

Conserved Domains (4) summary

cd00992
Location:85 → 165

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd07353
Location:2 → 80

harmonin_N; N-terminal protein-binding module of harmonin

TIGR02794
Location:302 → 383

tolA_full; TolA protein

pfam03879
Location:309 → 358

Cgr1; Cgr1 family
XM_017017075.2 → XP_016872564.1 harmonin isoform X10
XM_047426221.1 → XP_047282177.1 harmonin isoform X8
XM_047426219.1 → XP_047282175.1 harmonin isoform X5
XM_017017073.1 → XP_016872562.1 harmonin isoform X2
XM_017017074.1 → XP_016872563.1 harmonin isoform X4
XM_017017072.1 → XP_016872561.1 harmonin isoform X1
XM_047426222.1 → XP_047282178.1 harmonin isoform X9
XM_047426220.1 → XP_047282176.1 harmonin isoform X7
XM_011519834.3 → XP_011518136.1 harmonin isoform X6

Conserved Domains (4) summary

cd00992
Location:85 → 165

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd07353
Location:2 → 80

harmonin_N; N-terminal protein-binding module of harmonin

TIGR02794
Location:302 → 383

tolA_full; TolA protein

pfam03879
Location:316 → 358

Cgr1; Cgr1 family