TMTC3

transmembrane O-mannosyltransferase targeting cadherins 3, the group of Transmembrane and tetratricopeptide repeat containing|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 12:88142296-88199887

Links

ENSG00000139324 ∙ NCBI:160418 ∙ OMIM:617218 ∙ HGNC:26899 ∙ Uniprot:Q6ZXV5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• periventricular nodular heterotopia (Supportive), mode of inheritance: AD
• lissencephaly 8 (Strong), mode of inheritance: AR
• lissencephaly 8 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lissencephaly 8	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	Musculoskeletal; Neurologic; Ophthalmologic	27773428

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMTC3 gene.

• not_provided (152 variants)
• Inborn_genetic_diseases (88 variants)
• Lissencephaly_8 (21 variants)
• TMTC3-related_disorder (15 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMTC3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000181783.4. 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			4	44		48
missense		2	126	6	5	139
nonsense	3	2				5
start loss	1					1
frameshift	3	2	2			7
splice donor/acceptor (+/-2bp)		1				1
Total	7	7	132	50	5

Highest pathogenic variant AF is 0.0000260357

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMTC3	protein_coding	protein_coding	ENST00000266712	13	57592

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000463	1.00	125689	0	55	125744	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.62	364	462	0.788	0.0000217	5996
Missense in Polyphen		97	143.06	0.67804		1772
Synonymous	1.11	142	160	0.888	0.00000729	1716
Loss of Function	3.76	15	41.0	0.366	0.00000224	552

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000641	0.000576
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000129	0.000109
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000242	0.000237
Middle Eastern	0.000129	0.000109
South Asian	0.000279	0.000261
Other	0.000358	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the positive regulation of proteasomal protein degradation in the endoplasmic reticulum (ER), and the control of ER stress response. {ECO:0000269|PubMed:21603654}.
• Disease: DISEASE: Lissencephaly 8 (LIS8) [MIM:617255]: A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS8 patients manifest delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, hypotonia, cortical gyral abnormalities, and hypoplasia of the corpus callosum, brainstem and cerebellum. LIS8 inheritance is autosomal recessive. {ECO:0000269|PubMed:27773428}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.203

Intolerance Scores

• loftool: 0.780
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.49

Haploinsufficiency Scores

• pHI: 0.146
• hipred: N
• hipred_score: 0.488
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.687

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmtc3
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: response to endoplasmic reticulum stress;positive regulation of proteasomal protein catabolic process
• Cellular component: endoplasmic reticulum;integral component of membrane
• Molecular function: protein binding