TMTC2

transmembrane O-mannosyltransferase targeting cadherins 2, the group of Tetratricopeptide repeat domain containing|Transmembrane and tetratricopeptide repeat containing

Basic information

Region (hg38): 12:82686879-83134870

Links

ENSG00000179104 ∙ NCBI:160335 ∙ OMIM:615856 ∙ HGNC:25440 ∙ Uniprot:Q8N394 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nonsyndromic genetic hearing loss (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMTC2 gene.

• Inborn genetic diseases (33 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMTC2 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					2	2
missense			33		1	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	33	0	3

Variants in TMTC2

This is a list of pathogenic ClinVar variants found in the TMTC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-82687618-G-T		not specified	Uncertain significance (Dec 19, 2023)
12-82687623-G-A		not specified	Uncertain significance (May 09, 2023)
12-82687640-C-T			Benign (Jun 13, 2018)
12-82687660-A-G		not specified	Uncertain significance (Apr 06, 2022)
12-82857072-A-G		not specified	Uncertain significance (May 10, 2022)
12-82857122-C-T		not specified	Uncertain significance (Apr 26, 2023)
12-82857123-G-A		not specified	Uncertain significance (May 23, 2023)
12-82857227-C-T		not specified	Uncertain significance (Nov 29, 2021)
12-82857315-C-T		not specified	Uncertain significance (Jan 16, 2024)
12-82857326-G-T		not specified	Uncertain significance (Jul 05, 2023)
12-82857392-A-G		not specified	Uncertain significance (Apr 13, 2022)
12-82857429-C-G		not specified	Uncertain significance (Sep 17, 2021)
12-82857498-C-T		not specified	Uncertain significance (Jun 28, 2023)
12-82857528-T-C		not specified	Uncertain significance (Dec 01, 2022)
12-82857542-A-T		not specified	Uncertain significance (Feb 01, 2023)
12-82895995-A-G			Benign (Jun 21, 2018)
12-82896071-A-G		TMTC2-related disorder	Likely benign (Apr 11, 2023)
12-82896113-A-C		not specified	Uncertain significance (Mar 23, 2022)
12-82896113-A-G		not specified	Uncertain significance (Aug 12, 2021)
12-82896204-G-T		TMTC2-related disorder	Likely benign (Mar 22, 2023)
12-82896242-A-G		not specified	Uncertain significance (Aug 08, 2022)
12-82896259-A-C		not specified	Uncertain significance (Jul 10, 2023)
12-82896296-A-T		not specified	Uncertain significance (Sep 26, 2022)
12-82896320-A-G		not specified	Uncertain significance (Jun 03, 2022)
12-82896326-C-G		not specified	Uncertain significance (Oct 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMTC2	protein_coding	protein_coding	ENST00000321196	12	447991

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0225	0.977	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.539	420	452	0.929	0.0000243	5463
Missense in Polyphen		123	157.53	0.7808		1794
Synonymous	-0.0488	178	177	1.00	0.00000982	1633
Loss of Function	3.97	10	35.6	0.281	0.00000178	461

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000657	0.000657
Ashkenazi Jewish	0.000304	0.000298
East Asian	0.000165	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000975	0.0000967
Middle Eastern	0.000165	0.000163
South Asian	0.000230	0.000229
Other	0.000332	0.000326

dbNSFP

Source: dbNSFP

Intolerance Scores

• loftool: 0.336
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.91

Haploinsufficiency Scores

• pHI: 0.415
• hipred: Y
• hipred_score: 0.590
• ghis: 0.457

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.260

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmtc2

Gene ontology

• Biological process: calcium ion homeostasis
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
• Molecular function: protein binding