USH1G

USH1 protein network component sans, the group of Sterile alpha motif domain containing|Ankyrin repeat domain containing

Basic information

Region (hg38): 17:74916083-74923256

Links

ENSG00000182040 ∙ NCBI:124590 ∙ OMIM:607696 ∙ HGNC:16356 ∙ Uniprot:Q495M9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Usher syndrome type 1G (Strong), mode of inheritance: AR
• Usher syndrome type 1G (Definitive), mode of inheritance: AR
• Usher syndrome type 1 (Supportive), mode of inheritance: AR
• Usher syndrome type 1G (Strong), mode of inheritance: AR
• Usher syndrome type 1G (Definitive), mode of inheritance: AR
• Usher syndrome type 1G (Strong), mode of inheritance: AR
• Usher syndrome type 1 (Definitive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Usher syndrome, type 1G	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	12588794

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USH1G gene.

• not_provided (342 variants)
• Inborn_genetic_diseases (61 variants)
• Usher_syndrome_type_1G (59 variants)
• not_specified (40 variants)
• USH1G-related_disorder (14 variants)
• Retinal_dystrophy (6 variants)
• Usher_syndrome (6 variants)
• Usher_syndrome_type_1 (5 variants)
• Hearing_impairment (3 variants)
• Deafness (2 variants)
• Optic_atrophy (2 variants)
• Hearing_loss,_autosomal_recessive (2 variants)
• Rare_genetic_deafness (1 variants)
• Non-Syndromic_Hereditary_Hearing_Impairment (1 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_18A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USH1G gene is commonly pathogenic or not. These statistics are base on transcript: NM_000173477.5. 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			3	101		104
missense	3	5	219	13	1	241
nonsense	12	6				18
start loss						0
frameshift	27	11				38
splice donor/acceptor (+/-2bp)	1	1				2
Total	43	23	222	114	1

Highest pathogenic variant AF is 0.0003018044

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USH1G	protein_coding	protein_coding	ENST00000319642	3	7176

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000375	0.839	125697	0	27	125724	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.633	280	311	0.899	0.0000232	2962
Missense in Polyphen		103	124.85	0.82501		1273
Synonymous	2.13	111	143	0.774	0.0000110	970
Loss of Function	1.33	9	14.5	0.623	8.54e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000290	0.000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000985	0.0000967
Middle Eastern	0.000111	0.000109
South Asian	0.0000981	0.0000980
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal development and maintenance of cochlear hair cell bundles. 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 hearing. {ECO:0000269|PubMed:21709241}.
• Disease: DISEASE: Note=The first cases with non-syndromic sensorineural hearing loss based on mutations in USH1G. The hearing loss has an onset during early childhood, is progressive, and has a downsloping audiogram configuration. Ophthalmic and vestibular abnormalities are absent. {ECO:0000269|PubMed:25255398}.

Intolerance Scores

• loftool: 0.702
• rvis_EVS: 0.73
• rvis_percentile_EVS: 86.21

Haploinsufficiency Scores

• pHI: 0.164
• hipred: N
• hipred_score: 0.439
• ghis: 0.450

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.295

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ush1g
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); cellular phenotype

Gene ontology

• Biological process: sensory perception of sound;inner ear morphogenesis;photoreceptor cell maintenance;sensory perception of light stimulus;equilibrioception;inner ear receptor cell stereocilium organization
• Cellular component: photoreceptor inner segment;cytosol;plasma membrane;actin cytoskeleton;photoreceptor connecting cilium;ciliary basal body
• Molecular function: protein binding;spectrin binding;identical protein binding;protein homodimerization activity