TENM3

teneurin transmembrane protein 3, the group of MicroRNA protein coding host genes|Teneurin transmembrane protein family

Basic information

Region (hg38): 4:182143986-182803024

Previous symbols: [ "ODZ3" ]

Links

ENSG00000218336 ∙ NCBI:55714 ∙ OMIM:610083 ∙ HGNC:29944 ∙ Uniprot:Q9P273 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microphthalmia, isolated, with coloboma 9 (Strong), mode of inheritance: AR
• microphthalmia, isolated, with coloboma 9 (Moderate), mode of inheritance: AR
• microphthalmia, isolated, with coloboma (Supportive), mode of inheritance: AD
• microphthalmia, isolated, with coloboma 9 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, isolated, with coloboma 9	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	Craniofacial; Neurologic; Ophthalmologic	22766609; 29753094; 30513139

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TENM3 gene.

• not provided (213 variants)
• Inborn genetic diseases (99 variants)
• Microphthalmia, isolated, with coloboma 9 (17 variants)
• not specified (10 variants)
• MICROPHTHALMIA, SYNDROMIC 15 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TENM3 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				33	33	66
missense		2	122	9	5	138
nonsense	2					2
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			3	4	5	12
non coding			1	18	79	98
Total	2	2	124	60	117

Highest pathogenic variant AF is 0.0000131

Variants in TENM3

This is a list of pathogenic ClinVar variants found in the TENM3 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-182323716-C-T			Benign (Jun 29, 2018)
4-182323774-G-A			Benign (Oct 18, 2020)
4-182324032-A-G			Likely benign (Jun 20, 2018)
4-182324056-G-A			Likely benign (May 23, 2023)
4-182324110-T-G		Inborn genetic diseases	Uncertain significance (Feb 08, 2022)
4-182324138-T-A		Inborn genetic diseases	Uncertain significance (Jan 06, 2023)
4-182324225-A-G		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
4-182346337-T-A			Benign (Jun 26, 2018)
4-182346575-TA-T			Benign (May 17, 2021)
4-182346575-TAA-T			Likely benign (May 16, 2021)
4-182346631-C-CT			Benign (Feb 14, 2022)
4-182346665-C-G		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
4-182346680-G-A		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
4-182346710-G-T			Likely benign (Dec 09, 2023)
4-182346721-G-T			Benign (Dec 09, 2023)
4-182346733-C-T			Benign (Jan 23, 2024)
4-182346812-A-G		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
4-182346820-T-C			Likely benign (Aug 09, 2023)
4-182346832-G-T		TENM3-related disorder	Likely benign (Sep 29, 2022)
4-182346857-C-T			Benign (Jan 04, 2023)
4-182346858-T-A		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
4-182346948-T-C			Likely benign (Jun 28, 2022)
4-182346995-C-CG			Benign (Sep 04, 2018)
4-182346995-C-CGG			Benign (Sep 04, 2018)
4-182347021-C-T			Benign (Jun 26, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TENM3	protein_coding	protein_coding	ENST00000511685	27	659038

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000452	124610	0	32	124642	0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.30	1191	1.56e+3	0.765	0.0000945	17631
Missense in Polyphen		154	218.2	0.70578		1933
Synonymous	0.112	623	627	0.994	0.0000418	5310
Loss of Function	8.11	21	115	0.183	0.00000625	1331

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000212
Ashkenazi Jewish	0.000497	0.000497
East Asian	0.0000582	0.0000556
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000995	0.0000973
Middle Eastern	0.0000582	0.0000556
South Asian	0.000100	0.0000980
Other	0.000497	0.000496

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in neural development by regulating the establishment of proper connectivity within the nervous system. Acts in both pre- and postsynaptic neurons in the hippocampus to control the assembly of a precise topographic projection: required in both CA1 and subicular neurons for the precise targeting of proximal CA1 axons to distal subiculum, probably by promoting homophilic cell adhesion. Required for proper dendrite morphogenesis and axon targeting in the vertebrate visual system, thereby playing a key role in the development of the visual pathway. Regulates the formation in ipsilateral retinal mapping to both the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). May also be involved in the differentiation of the fibroblast-like cells in the superficial layer of mandibular condylar cartilage into chondrocytes. {ECO:0000250|UniProtKB:Q9WTS6}.
• Disease: DISEASE: Microphthalmia, isolated, with coloboma, 9 (MCOPCB9) [MIM:615145]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). {ECO:0000269|PubMed:22766609, ECO:0000269|PubMed:27103084}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: -3.46
• rvis_percentile_EVS: 0.36

Haploinsufficiency Scores

• pHI: 0.487
• hipred: Y
• hipred_score: 0.685
• ghis: 0.615

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tenm3
• 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); 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)

Zebrafish Information Network

• Gene name: tenm3
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: homophilic cell adhesion via plasma membrane adhesion molecules;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;signal transduction;positive regulation of neuron projection development;camera-type eye morphogenesis;neuron development;regulation of homophilic cell adhesion
• Cellular component: integral component of plasma membrane;membrane;axon;neuron projection
• Molecular function: protein homodimerization activity;protein heterodimerization activity;cell adhesion molecule binding