WHRN whirlin [Homo sapiens (human)] - Gene

Summary

Official Symbol: WHRNprovided by HGNC
Official Full Name: whirlinprovided by HGNC
Primary source: HGNC:HGNC:16361
See related: Ensembl:ENSG00000095397 MIM:607928; AllianceGenome:HGNC:16361
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: WI; CIP98; USH2D; DFNB31; PDZD7B
Summary: This gene is thought to function in the organization and stabilization of sterocilia elongation and actin cystoskeletal assembly, based on studies of the related mouse gene. Mutations in this gene have been associated with autosomal recessive non-syndromic deafness and Usher Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
Expression: Broad expression in adrenal (RPKM 14.4), testis (RPKM 9.7) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q32

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (114402080..114505473, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (126594499..126697864, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (117164360..117267753, complement)

Chromosome 9 - NC_000009.12 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
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?

Novel pathogenic WHRN variant causing hearing loss in a moroccan family.
Title: Novel pathogenic WHRN variant causing hearing loss in a moroccan family.
Phase separation-mediated condensation of Whirlin-Myo15-Eps8 stereocilia tip complex.
Title: Phase separation-mediated condensation of Whirlin-Myo15-Eps8 stereocilia tip complex.
Folding and Misfolding of a PDZ Tandem Repeat.
Title: Folding and Misfolding of a PDZ Tandem Repeat.
Usher syndrome and non-syndromic deafness: Functions of different whirlin isoforms in the cochlea, vestibular organs, and retina.
Title: Usher syndrome and non-syndromic deafness: Functions of different whirlin isoforms in the cochlea, vestibular organs, and retina.
whirlin-espin interaction is important for the architecture of the USH2 complex and actin bundles cross-linked by espin. Our demonstration of whirlin N-terminal fragment interaction with espin, is significantly novel, providing insight into how these two proteins interact to form the USH2 complex.
Title: Identification of whirlin domains interacting with espin: A study of the mechanism of Usher syndrome type II.
two novel mutations in the WHRN and TMC1 genes are responsible for founder effects of hereditary hemochromatosis, Wilson s disease, the long QT syndrome and autosomal recessive deafness in a Swedish pedigree
Title: Common founder effects of hereditary hemochromatosis, Wilson´s disease, the long QT syndrome and autosomal recessive deafness caused by two novel mutations in the WHRN and TMC1 genes.
Protein-protein interaction assays and co-expression of complex partners reveal that pathogenic mutations in USH1G severely affect formation of the SANS/ush2a/whirlin complex. Translational read-through drug treatment, targeting the c.728C > A (p.S243X) nonsense mutation, restored SANS scaffold function. We conclude that USH1 and USH2 proteins function together in higher order protein complexes.
Title: Characterization of the ternary Usher syndrome SANS/ush2a/whirlin protein complex.
Data indicate that that CIB2 localizes to stereocilia and interacts with the USH proteins myosin VIIa and whirlin, suggesting CIB2 is a Ca2+-buffering protein essential for calcium homeostasis in the mechanosensory stereocilia of inner ear hair cells.
Title: Usher proteins in inner ear structure and function.
In Spain, USH2A and GPR98 are responsible for 95.8% and 5.2% of Usher syndrome 2 mutated cases, respectively. DFNB31 plays a minor role in the Spanish population. There was a group of patients in whom no mutation was found.
Title: The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort.
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.

Submit: New GeneRIF Correction See all GeneRIFs (18)

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 31 MedGen: C1846839 OMIM: 607084 GeneReviews: Genetic Hearing Loss Overview	Compare labs
Usher syndrome type 2D MedGen: C1568249 OMIM: 611383 GeneReviews: Usher Syndrome Type II	Compare labs

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Propensity score-based nonparametric test revealing genetic variants underlying bipolar disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

D9S314 (e-PCR)
- UniSTS:153122

RH99310 (e-PCR)
- UniSTS:90925

SHGC-145040 (e-PCR)
- UniSTS:174381

SHGC-145954 (e-PCR)
- UniSTS:174899

SHGC-154470 (e-PCR)
- UniSTS:184956

D9S1824 (e-PCR), detects polymorphism
- UniSTS:58794

SHGC-156144 (e-PCR)
- UniSTS:185006

D9S1776 (e-PCR), detects polymorphism
- UniSTS:51141

D9S1682 (e-PCR), detects polymorphism
- UniSTS:49871

D9S2024 (e-PCR)
- UniSTS:60889

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in auditory receptor cell stereocilium organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in cerebellar Purkinje cell layer formation	IEA Inferred from Electronic Annotation more info
involved_in detection of mechanical stimulus involved in sensory perception of sound	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of localization in cell	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within establishment of protein localization	ISS Inferred from Sequence or Structural Similarity more info
involved_in inner ear receptor cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in inner ear receptor cell stereocilium organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in paranodal junction maintenance	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in retina homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retina homeostasis	ISS Inferred from Sequence or Structural Similarity 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
part_of USH2 complex	ISS Inferred from Sequence or Structural Similarity more info
located_in actin filament	IEA Inferred from Electronic Annotation more info
located_in ciliary basal body	IEA Inferred from Electronic Annotation more info
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 growth cone	IEA Inferred from Electronic Annotation more info
colocalizes_with neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in periciliary membrane compartment	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with photoreceptor connecting cilium	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with photoreceptor inner segment	IBA Inferred from Biological aspect of Ancestor more info
colocalizes_with photoreceptor inner 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 stereocilia ankle link	ISS Inferred from Sequence or Structural Similarity more info
part_of stereocilia ankle link complex	IBA Inferred from Biological aspect of Ancestor more info
part_of stereocilia ankle link complex	ISS Inferred from Sequence or Structural Similarity more info
located_in stereocilium	ISS Inferred from Sequence or Structural Similarity more info
is_active_in stereocilium tip	IBA Inferred from Biological aspect of Ancestor more info
located_in stereocilium tip	ISS Inferred from Sequence or Structural Similarity more info
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: whirlin

Names: CASK-interacting protein CIP98; autosomal recessive deafness type 31 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_016700.1 RefSeqGene

Range

4984..108377

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1094

mRNA and Protein(s)

NM_001083885.3 → NP_001077354.2 whirlin isoform 2

See identical proteins and their annotated locations for NP_001077354.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple differences in the presence and absence of exons at its 5' end, compared to variant 1. These differences produce a unique 5' UTR and cause translation initiation at a downstream start codon, compared to variant 1. The encoded protein (isoform 2) is shorter than isoform 1.

Source sequence(s)

AL110228, BC136416, BC142614, DA502065

Consensus CDS

CCDS43870.1

UniProtKB/TrEMBL

A0A669KBJ1

Related

ENSP00000265134.6, ENST00000265134.10

Conserved Domains (2) summary

cd00992
Location:433 → 504

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) ...

cd07357
Location:36 → 116

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains
NM_001173425.2 → NP_001166896.1 whirlin isoform 3

See identical proteins and their annotated locations for NP_001166896.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate, in-frame splice site in the 3' coding region, compared to variant 1. The encoded protein (isoform 3) is shorter than isoform 1.

Source sequence(s)

AL138895, BC014524, BC136416, BC142614, BC142684

UniProtKB/TrEMBL

B9EGE6

Conserved Domains (4) summary

cd00992
Location:277 → 357

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) ...

cd07356
Location:37 → 112

HN_L-whirlin_R1_like; first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains

cd07357
Location:419 → 499

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains

pfam05109
Location:516 → 803

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
NM_001346890.1 → NP_001333819.1 whirlin isoform 4 precursor

Status: REVIEWED

Source sequence(s)

AL138895, KF459656, KF459658

UniProtKB/TrEMBL

A0A669KBJ1

Related

ENST00000674048.1
NM_015404.4 → NP_056219.3 whirlin isoform 1

See identical proteins and their annotated locations for NP_056219.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AL138895, BC136416, BC142614, BC142684

Consensus CDS

CCDS6806.1

UniProtKB/Swiss-Prot

A0A0C4DFT9, A5PKU1, A5PKZ9, Q5TAU9, Q5TAV0, Q5TAV1, Q5TAV2, Q96MZ9, Q9H9F4, Q9P202, Q9UFZ3

Related

ENSP00000354623.3, ENST00000362057.4

Conserved Domains (4) summary

cd00992
Location:277 → 357

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) ...

cd07356
Location:37 → 112

HN_L-whirlin_R1_like; first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains

cd07357
Location:419 → 499

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains

cl25496
Location:516 → 804

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

114402080..114505473 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047423168.1 → XP_047279124.1 whirlin isoform X10
XM_047423165.1 → XP_047279121.1 whirlin isoform X7
XM_047423164.1 → XP_047279120.1 whirlin isoform X6
XM_047423166.1 → XP_047279122.1 whirlin isoform X8
XM_047423163.1 → XP_047279119.1 whirlin isoform X4

UniProtKB/TrEMBL

B9EGE6

Conserved Domains (4) summary

cd00992
Location:277 → 357

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) ...

cd07356
Location:37 → 112

HN_L-whirlin_R1_like; first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains

cd07357
Location:419 → 499

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains

pfam05109
Location:516 → 803

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
XM_047423161.1 → XP_047279117.1 whirlin isoform X3

UniProtKB/Swiss-Prot

A0A0C4DFT9, A5PKU1, A5PKZ9, Q5TAU9, Q5TAV0, Q5TAV1, Q5TAV2, Q96MZ9, Q9H9F4, Q9P202, Q9UFZ3
XM_011518485.2 → XP_011516787.1 whirlin isoform X1

See identical proteins and their annotated locations for XP_011516787.1

Conserved Domains (3) summary

cd00992
Location:277 → 357

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) ...

cd07356
Location:37 → 112

HN_L-whirlin_R1_like; first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains

cd07357
Location:419 → 499

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains
XM_047423169.1 → XP_047279125.1 whirlin isoform X11
XM_011518487.3 → XP_011516789.1 whirlin isoform X5
XM_047423167.1 → XP_047279123.1 whirlin isoform X9
XM_011518486.3 → XP_011516788.1 whirlin isoform X2

Conserved Domains (3) summary

cd00992
Location:277 → 357

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) ...

cd07356
Location:37 → 112

HN_L-whirlin_R1_like; first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains

cd07357
Location:419 → 499

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains
XM_047423171.1 → XP_047279127.1 whirlin isoform X13
XM_047423170.1 → XP_047279126.1 whirlin isoform X12
XM_011518492.3 → XP_011516794.1 whirlin isoform X15

See identical proteins and their annotated locations for XP_011516794.1

UniProtKB/TrEMBL

A0A8V8TQ31

Related

ENSP00000514397.1, ENST00000699486.1

Conserved Domains (3) summary

cd00992
Location:277 → 357

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) ...

cd07356
Location:37 → 112

HN_L-whirlin_R1_like; first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains

cd07357
Location:419 → 499

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains
XM_047423173.1 → XP_047279129.1 whirlin isoform X14
XM_047423174.1 → XP_047279130.1 whirlin isoform X17
XM_011518491.4 → XP_011516793.1 whirlin isoform X15

See identical proteins and their annotated locations for XP_011516793.1

UniProtKB/TrEMBL

A0A8V8TQ31

Conserved Domains (3) summary

cd00992
Location:277 → 357

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) ...

cd07356
Location:37 → 112

HN_L-whirlin_R1_like; first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains

cd07357
Location:419 → 499

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains
XM_011518494.4 → XP_011516796.1 whirlin isoform X16

UniProtKB/TrEMBL

A0A8V8TQ31

Conserved Domains (3) summary

cd00992
Location:277 → 357

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) ...

cd07356
Location:37 → 112

HN_L-whirlin_R1_like; first harmonin_N_like domain (repeat 1) of the long isoform of whirlin, and related domains

cd07357
Location:419 → 499

HN_L-whirlin_R2_like; second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains