USH1C

USH1 protein network component harmonin, the group of PDZ domain containing

Basic information

Region (hg38): 11:17493895-17544416

Previous symbols: [ "DFNB18" ]

Links

ENSG00000006611 ∙ NCBI:10083 ∙ OMIM:605242 ∙ HGNC:12597 ∙ Uniprot:Q9Y6N9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Usher syndrome type 1C (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 18A (Limited), mode of inheritance: AR
• Usher syndrome type 1C (Definitive), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• Usher syndrome type 1 (Supportive), mode of inheritance: AR
• Usher syndrome type 1C (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 18A (Moderate), mode of inheritance: AR
• Usher syndrome type 1C (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 18A (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 18A (Limited), mode of inheritance: Unknown
• Usher syndrome type 1C (Strong), mode of inheritance: AR
• Usher syndrome type 1 (Definitive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Usher syndrome, type IC; Deafness, autosomal recessive 18A	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	5937908; 9653658; 10973248; 10973247; 12107438; 2136232; 23251578
Hearing loss has been described as late-onset in some individuals

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USH1C gene.

• not_provided (1147 variants)
• Usher_syndrome_type_1C (344 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_18A (206 variants)
• not_specified (145 variants)
• Inborn_genetic_diseases (92 variants)
• USH1C-related_disorder (36 variants)
• Usher_syndrome_type_1 (34 variants)
• Retinal_dystrophy (11 variants)
• Usher_syndrome (8 variants)
• Hearing_impairment (7 variants)
• Optic_atrophy (3 variants)
• Usher_syndrome_type_2 (3 variants)
• Rare_genetic_deafness (2 variants)
• Retinitis_pigmentosa (2 variants)
• Hearing_loss,_autosomal_recessive (2 variants)
• Meniere_disease (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USH1C gene is commonly pathogenic or not. These statistics are base on transcript: NM_000153676.4. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	1	12	283	8	305
missense	2	7	348	59	2	418
nonsense	16	11	14	3		44
start loss		1				1
frameshift	32	34	18	1		85
splice donor/acceptor (+/-2bp)	19	53	13	3		88
Total	70	107	405	349	10

Highest pathogenic variant AF is 0.0003104574

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USH1C	protein_coding	protein_coding	ENST00000005226	27	50522

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.97e-18	0.865	125446	1	301	125748	0.00120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.874	583	527	1.11	0.0000343	5784
Missense in Polyphen		219	186.65	1.1733		2010
Synonymous	-1.92	241	206	1.17	0.0000129	1785
Loss of Function	2.22	36	53.5	0.672	0.00000297	606

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00990	0.00987
Ashkenazi Jewish	0.00199	0.00199
East Asian	0.00109	0.00109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000660	0.000651
Middle Eastern	0.00109	0.00109
South Asian	0.000298	0.000294
Other	0.000817	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (By similarity). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018). {ECO:0000250|UniProtKB:Q9ES64, ECO:0000269|PubMed:24725409, ECO:0000269|PubMed:26812018}.
• Disease: DISEASE: Usher syndrome 1C (USH1C) [MIM:276904]: 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). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness. {ECO:0000269|PubMed:10973247}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 18A (DFNB18A) [MIM:602092]: 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:12107438}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.169

Intolerance Scores

• loftool: 0.926
• rvis_EVS: -0.41
• rvis_percentile_EVS: 25.87

Haploinsufficiency Scores

• pHI: 0.0784
• hipred: Y
• hipred_score: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.666

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: Ush1c
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); digestive/alimentary 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); hearing/vestibular/ear phenotype; vision/eye phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: ush1c
• Affected structure: retinal cone cell
• Phenotype tag: abnormal
• Phenotype quality: detached from

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;sensory perception of sound;parallel actin filament bundle assembly;regulation of microvillus length;cellular protein-containing complex assembly;inner ear morphogenesis;inner ear auditory receptor cell differentiation;photoreceptor cell maintenance;retinal cone cell development;sensory perception of light stimulus;equilibrioception;actin filament bundle assembly;inner ear receptor cell stereocilium organization;protein localization to microvillus;brush border assembly
• Cellular component: photoreceptor outer segment;photoreceptor inner segment;stereocilia ankle link;stereocilia ankle link complex;cytoplasm;cytosol;cytoskeleton;plasma membrane;microvillus;brush border;photoreceptor connecting cilium;stereocilium;stereocilium tip;apical part of cell;synapse
• Molecular function: protein binding;spectrin binding;actin filament binding