WHRN

whirlin, the group of PDZ domain containing|USH2 complex

Basic information

Region (hg38): 9:114402078-114505473

Previous symbols: [ "DFNB31" ]

Links

ENSG00000095397 ∙ NCBI:25861 ∙ OMIM:607928 ∙ HGNC:16361 ∙ Uniprot:Q9P202 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Usher syndrome type 2D (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 31 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• Usher syndrome type 2 (Supportive), mode of inheritance: AR
• Usher syndrome type 2D (Moderate), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 31 (Moderate), mode of inheritance: AR
• Usher syndrome type 2D (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 31 (Strong), mode of inheritance: AR
• Usher syndrome type 2D (Strong), mode of inheritance: AR
• Usher syndrome type 2D (Definitive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Usher syndrome, type 2D; Deafness, autosomal recessive 31	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	12833159; 17171570

ClinVar

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

• not provided (23 variants)
• Usher syndrome type 2D (3 variants)
• Usher syndrome (2 variants)
• Autosomal recessive nonsyndromic hearing loss 31 (2 variants)
• Rare genetic deafness (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WHRN 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			8	183	6	197
missense			343	7	10	360
nonsense	9	2	2			13
start loss			2			2
frameshift	18	2				20
inframe indel			5			5
splice donor/acceptor (+/-2bp)		3	1			4
splice region			11	13		24
non coding			50	75	31	156
Total	27	7	411	265	47

Highest pathogenic variant AF is 0.0000467

Variants in WHRN

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

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

Position	Type	Phenotype	Significance	ClinVar
9-114402121-A-G		Usher syndrome type 2D • Autosomal recessive nonsyndromic hearing loss 31	Uncertain significance (Jan 13, 2018)
9-114402141-T-C		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Uncertain significance (Jan 13, 2018)
9-114402171-G-A		Usher syndrome type 2D • Autosomal recessive nonsyndromic hearing loss 31	Uncertain significance (Mar 30, 2018)
9-114402200-G-A		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Uncertain significance (Jan 13, 2018)
9-114402259-A-G		Usher syndrome type 2D • Autosomal recessive nonsyndromic hearing loss 31	Uncertain significance (Jan 12, 2018)
9-114402316-A-C		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Benign (Apr 27, 2017)
9-114402397-G-C		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Uncertain significance (Jan 13, 2018)
9-114402415-G-T		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Uncertain significance (Jan 12, 2018)
9-114402428-A-AG		Retinitis pigmentosa-deafness syndrome • Hearing loss, autosomal recessive	Uncertain significance (Jun 14, 2016)
9-114402566-T-A		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Uncertain significance (Jan 13, 2018)
9-114402567-T-C		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Uncertain significance (Jan 13, 2018)
9-114402579-G-A		Usher syndrome type 2D • Autosomal recessive nonsyndromic hearing loss 31	Uncertain significance (Jan 12, 2018)
9-114402598-C-T		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Uncertain significance (Jan 13, 2018)
9-114402605-T-C		Usher syndrome type 2D • Autosomal recessive nonsyndromic hearing loss 31	Uncertain significance (Jan 12, 2018)
9-114402628-G-T		Usher syndrome type 2D • Autosomal recessive nonsyndromic hearing loss 31	Uncertain significance (Jan 13, 2018)
9-114402703-G-A		Usher syndrome type 2D • Autosomal recessive nonsyndromic hearing loss 31	Conflicting classifications of pathogenicity (May 20, 2020)
9-114402717-G-C		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Conflicting classifications of pathogenicity (May 20, 2020)
9-114402725-A-C		Usher syndrome type 2D • Autosomal recessive nonsyndromic hearing loss 31	Uncertain significance (Jan 13, 2018)
9-114402756-A-G		not specified • Usher syndrome type 2D;Autosomal recessive nonsyndromic hearing loss 31	Uncertain significance (Feb 16, 2023)
9-114402777-T-G			Uncertain significance (May 13, 2022)
9-114402788-T-G		Autosomal recessive nonsyndromic hearing loss 31 • Usher syndrome type 2D	Uncertain significance (Nov 20, 2021)
9-114402792-T-C			Uncertain significance (Mar 18, 2022)
9-114402800-C-T			Uncertain significance (Aug 06, 2022)
9-114402801-G-A			Uncertain significance (Aug 09, 2022)
9-114402801-G-C			Uncertain significance (Feb 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WHRN	protein_coding	protein_coding	ENST00000362057	12	103371

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000765	0.999	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.325	580	558	1.04	0.0000378	5703
Missense in Polyphen		192	200.8	0.95617		2122
Synonymous	-0.445	264	255	1.04	0.0000184	2053
Loss of Function	2.94	12	29.1	0.412	0.00000146	330

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000272	0.000272
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000547	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000298	0.000290
Middle Eastern	0.0000547	0.0000544
South Asian	0.000361	0.000359
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear. {ECO:0000250}.
• Disease: DISEASE: Deafness, autosomal recessive, 31 (DFNB31) [MIM:607084]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:11973626, ECO:0000269|PubMed:12833159, ECO:0000269|PubMed:15841483}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Usher syndrome 2D (USH2D) [MIM:611383]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa and 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:17171570}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.165

Intolerance Scores

• rvis_EVS: 0.64
• rvis_percentile_EVS: 83.65

Haploinsufficiency Scores

• pHI: 0.307
• hipred: Y
• hipred_score: 0.622
• ghis: 0.474

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Whrn
• Phenotype: reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; hearing/vestibular/ear 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); vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: retina homeostasis;sensory perception of sound;positive regulation of gene expression;cerebellar Purkinje cell layer formation;establishment of protein localization;detection of mechanical stimulus involved in sensory perception of sound;sensory perception of light stimulus;auditory receptor cell stereocilium organization;inner ear receptor cell stereocilium organization;paranodal junction maintenance
• Cellular component: photoreceptor inner segment;stereocilia ankle link;stereocilia ankle link complex;cytoplasm;actin filament;plasma membrane;growth cone;photoreceptor connecting cilium;stereocilium;stereocilium tip;ciliary basal body;neuronal cell body;periciliary membrane compartment;USH2 complex
• Molecular function: protein binding;protein homodimerization activity;protein heterodimerization activity