TMIE

transmembrane inner ear

Basic information

Region (hg38): 3:46694528-46710886

Previous symbols: [ "DFNB6" ]

Links

ENSG00000181585 ∙ NCBI:259236 ∙ OMIM:607237 ∙ HGNC:30800 ∙ Uniprot:Q8NEW7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 6 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 6 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 6 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 6	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	12145746; 19438934

ClinVar

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

• not provided (2 variants)
• Autosomal recessive nonsyndromic hearing loss 6 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMIE 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			1	7		8
missense		3	23	1		27
nonsense		1				1
start loss						0
frameshift	1	1	1			3
inframe indel			1	3	1	5
splice donor/acceptor (+/-2bp)	1					1
splice region		1			1	2
non coding			20	11	17	48
Total	2	5	46	22	18

Highest pathogenic variant AF is 0.0000413

Variants in TMIE

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

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

Position	Type	Phenotype	Significance	ClinVar
3-46701031-GC-G			Likely benign (Jan 06, 2019)
3-46701031-G-GC			Benign (Aug 21, 2019)
3-46701033-C-A			Benign (Dec 10, 2018)
3-46701039-C-G			Likely benign (Jan 13, 2019)
3-46701257-G-A			Benign (Nov 12, 2018)
3-46701258-C-A			Benign (Nov 12, 2018)
3-46701259-A-T			Benign (Nov 29, 2018)
3-46701334-G-A		Autosomal recessive nonsyndromic hearing loss 6	Uncertain significance (Jan 12, 2018)
3-46701415-C-T		Autosomal recessive nonsyndromic hearing loss 6	Uncertain significance (Jan 13, 2018)
3-46701451-C-A		Autosomal recessive nonsyndromic hearing loss 6 • not specified	Benign/Likely benign (Jan 13, 2018)
3-46701480-G-T		Autosomal recessive nonsyndromic hearing loss 6	Uncertain significance (Jan 13, 2018)
3-46701492-C-G		Inborn genetic diseases	Uncertain significance (Aug 23, 2022)
3-46701492-C-T		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
3-46701501-C-G			Uncertain significance (Mar 15, 2023)
3-46701509-G-A		Inborn genetic diseases	Uncertain significance (Apr 26, 2024)
3-46701517-C-T			Likely benign (Apr 13, 2023)
3-46701518-T-C		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
3-46701521-G-T		not specified • Autosomal recessive nonsyndromic hearing loss 6 • Inborn genetic diseases	Uncertain significance (May 29, 2024)
3-46701527-G-A		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 17, 2022)
3-46701536-G-A		Inborn genetic diseases	Uncertain significance (Mar 27, 2023)
3-46701541-C-T			Likely benign (Dec 30, 2021)
3-46701541-CG-C			Pathogenic (Apr 11, 2023)
3-46701545-G-C		Inborn genetic diseases	Uncertain significance (Mar 18, 2024)
3-46701546-T-A			Likely benign (Sep 18, 2023)
3-46701551-C-T		Autosomal recessive nonsyndromic hearing loss 6	Uncertain significance (Jun 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMIE	protein_coding	protein_coding	ENST00000326431	4	9554

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000775	0.325	124840	0	18	124858	0.0000721

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0515	74	75.3	0.983	0.00000513	993
Missense in Polyphen		31	32.024	0.96802		287
Synonymous	0.867	25	31.2	0.802	0.00000211	316
Loss of Function	-0.114	6	5.71	1.05	3.31e-7	80

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000115
Middle Eastern	0.0000556	0.0000556
South Asian	0.000163	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Unknown. The protein may play some role in a cellular membrane location. May reside within an internal membrane compartment and function in pathways such as those involved in protein and/or vesicle trafficking. Alternatively, the mature protein may be localized in the plasma membrane and serve as a site of interaction for other molecules through its highly charged C-terminal domain.

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.493
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.190
• hipred: N
• hipred_score: 0.251
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmie
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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

Zebrafish Information Network

• Gene name: tmie
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: sensory perception of sound;inner ear morphogenesis
• Cellular component: integral component of membrane