TENM3

protein-coding

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

Gene summary

This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

Previous symbols:

ODZ3

MANE transcript

NM_001080477.4

Inheritance

AR, AD

ClinVar variants

P:15U:409B:132

Top phenotype

Microphthalmia/coloboma 9

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr4:182,143,987-182,803,024

External References & Databases

Ensembl (ENSG00000218336)

Transcript & Mutation Effects

hg38 • Region Span ~659.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microphthalmia, isolated, with coloboma 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014059

Submitter: Labcorp Genetics (formerly Invitae)

microphthalmia, isolated, with coloboma 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014059

Submitter: G2P

microphthalmia, isolated, with coloboma 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014059

Submitter: PanelApp Australia

microphthalmia, isolated, with coloboma 9MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014059

Submitter: Ambry Genetics

microphthalmia, isolated, with colobomaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000170

Submitter: Orphanet

Clinical Genomic Database (CGD)

Microphthalmia/coloboma 9AR

Manifestation: Craniofacial; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 22766609; 29753094; 30513139

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TENM3 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 356

not providedTotal: 217

TENM3-related disorderTotal: 38

not specifiedTotal: 31

Microphthalmia, isolated, with coloboma 9Total: 23

Meniere diseaseTotal: 5

MICROPHTHALMIA, SYNDROMIC 15Total: 4

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080477.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	85 clinvar	22 clinvar	109
missense		2 clinvar	404 clinvar	20 clinvar	5 clinvar	431
nonsense	3 clinvar	3 clinvar				6
start loss						0
frameshift	2 clinvar	3 clinvar	1 clinvar			6
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	2 clinvar			4
Total	6	9	409	105	27	556

Highest pathogenic variant AF is 0.000014397767

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080477.4	RefSeq	NP_001073946.1	27	MANE Select
ENST00000511685.6	Ensembl	ENSP00000424226.1	27	MANE Select
NM_001415960.1	RefSeq	NP_001402889.1	26	Standard
NM_001415961.1	RefSeq	NP_001402890.1	25	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tenm3	Danio rerio	Structure: retinal ganglion cell Quality: process quality abnormal

Gene / Model

Organism

Observed Phenotype

tenm3

Danio rerio

Structure: retinal ganglion cell

Quality: process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

Molecular Function

protein homodimerization activity
protein heterodimerization activity
cell adhesion molecule binding

Cellular Component

integral component of plasma membrane
membrane
axon
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000511685
Coding exons: 27
Length: 659038
Individuals with no LoFs: 124610
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 124642
p: 0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.30	1191	1.56e+3	0.765	0.0000945	17631
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.000058	0.000056	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00010	0.000097	rare
South Asian	0.00010	0.000098	rare
Other	0.00050	0.00050	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N

Gene Damage Prediction

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