TMTC4

transmembrane O-mannosyltransferase targeting cadherins 4, the group of Tetratricopeptide repeat domain containing|Transmembrane and tetratricopeptide repeat containing

Basic information

Region (hg38): 13:100603625-100675093

Links

ENSG00000125247 ∙ NCBI:84899 ∙ OMIM:618203 ∙ HGNC:25904 ∙ Uniprot:Q5T4D3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 122	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	37943620

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMTC4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMTC4 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		1
missense			59	4		63
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	60	5	0

Variants in TMTC4

This is a list of pathogenic ClinVar variants found in the TMTC4 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-100605020-C-T		not specified	Uncertain significance (Oct 08, 2024)
13-100605070-G-T		not specified	Uncertain significance (Dec 10, 2024)
13-100605076-A-C		not specified	Uncertain significance (Apr 12, 2023)
13-100605079-T-C		not specified	Uncertain significance (Jan 30, 2024)
13-100605095-A-G		not specified	Uncertain significance (Jan 06, 2023)
13-100605122-C-G		not specified	Uncertain significance (Jan 03, 2024)
13-100606423-G-A		not specified	Uncertain significance (Aug 20, 2024)
13-100612442-T-C		not specified	Uncertain significance (Apr 12, 2022)
13-100612493-C-T		not specified	Uncertain significance (Nov 25, 2024)
13-100614325-C-T		not specified	Uncertain significance (Nov 13, 2024)
13-100614366-G-A		not specified	Uncertain significance (Mar 21, 2022)
13-100614376-C-T		not specified	Uncertain significance (Oct 25, 2023)
13-100614415-G-A		not specified	Uncertain significance (May 31, 2024)
13-100614417-T-C		not specified	Uncertain significance (Oct 19, 2024)
13-100625548-T-C		not specified	Uncertain significance (Sep 06, 2022)
13-100625593-C-T		not specified	Uncertain significance (Mar 01, 2024)
13-100625620-C-T		not specified	Uncertain significance (Feb 27, 2023)
13-100625627-G-C		not specified	Uncertain significance (Apr 20, 2023)
13-100625651-T-C		not specified	Uncertain significance (Jan 17, 2023)
13-100625659-G-T		not specified	Uncertain significance (Sep 22, 2023)
13-100625663-C-T		not specified	Uncertain significance (Dec 14, 2021)
13-100626074-A-C		not specified	Uncertain significance (Jul 13, 2022)
13-100626083-C-T		not specified	Uncertain significance (Dec 07, 2021)
13-100626091-T-G		not specified	Uncertain significance (Aug 20, 2024)
13-100626092-C-A		not specified	Uncertain significance (Sep 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMTC4	protein_coding	protein_coding	ENST00000342624	18	71167

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.86e-9	0.995	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.185	428	439	0.975	0.0000256	4947
Missense in Polyphen		122	124.42	0.98056		1392
Synonymous	0.0400	189	190	0.996	0.0000123	1520
Loss of Function	2.61	20	37.1	0.538	0.00000166	450

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000914	0.000902
Ashkenazi Jewish	0.00	0.00
East Asian	0.000275	0.000272
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000275	0.000272
South Asian	0.000236	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.482
• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.2

Haploinsufficiency Scores

• pHI: 0.128
• hipred: N
• hipred_score: 0.492
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.428

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmtc4
• 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Cellular component: integral component of membrane