TENM4

protein-coding

teneurin transmembrane protein 4, the group of MicroRNA protein coding host genes|Teneurin transmembrane protein family

Gene summary

The protein encoded by this gene plays a role in establishing proper neuronal connectivity during development. Defects in this gene have been associated with hereditary essential tremor-5. [provided by RefSeq, Oct 2016]

Previous symbols:

ODZ4

MANE transcript

NM_001098816.3

Inheritance

ClinVar variants

P:3U:557B:146

Top phenotype

Tremor, hereditary essential, 5

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr11:78,652,829-79,441,030

External References & Databases

Ensembl (ENSG00000149256)

Transcript & Mutation Effects

hg38 • Region Span ~788.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

tremor, hereditary essential, 5STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014756

Submitter: Labcorp Genetics (formerly Invitae)

tremor, hereditary essential, 5LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014756

Submitter: Ambry Genetics

tremor, hereditary essential, 5MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014756

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

Clinical Genomic Database (CGD)

Tremor, hereditary essential, 5AD

Manifestation: Neurologic

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: 26188006

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TENM4 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 535

not providedTotal: 191

TENM4-related disorderTotal: 81

Tremor, hereditary essential, 5Total: 33

Inborn genetic diseasesTotal: 3

EBV-positive nodal T- and NK-cell lymphomaTotal: 2

Cleft palateTotal: 1

Essential tremorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001098816.3. 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			6 clinvar	78 clinvar	15 clinvar	99
missense	2 clinvar		538 clinvar	38 clinvar	15 clinvar	593
nonsense			5 clinvar			5
start loss						0
frameshift		1 clinvar	2 clinvar			3
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	2	1	557	116	30	706

Highest pathogenic variant AF is 0.000002736622

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001098816.3	RefSeq	NP_001092286.2	30	MANE Select
ENST00000278550.12	Ensembl	ENSP00000278550.7	30	MANE Select
ENST00000527736.5	Ensembl	ENSP00000433535.1	1	Standard
ENST00000530738.1	Ensembl	ENSP00000431711.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tenm4	Danio rerio	Structure: motor neuron Quality: branchiness abnormal

Gene / Model

Organism

Observed Phenotype

tenm4

Danio rerio

Structure: motor neuron

Quality: branchiness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

gastrulation with mouth forming second
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
signal transduction
regulation of myelination
positive regulation of myelination

Molecular Function

protein homodimerization activity
protein heterodimerization activity
cell adhesion molecule binding

Cellular Component

nucleus
cytoplasm
plasma membrane
integral component of plasma membrane
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000278550
Coding exons: 30
Length: 788117
Individuals with no LoFs: 124637
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 124650
p: 0.0000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.73	1341	1.65e+3	0.811	0.000105	18142
Missense (PolyPhen)		308	483.35	0.63722		5101
Synonymous	2.38	601	680	0.884	0.0000445	5534
Loss of Function	8.51	11	105	0.105	0.00000538	1217

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Plays a role in the establishment of the anterior-posterior axis during gastrulation. Regulates the differentiation and cellular process formation of oligodendrocytes and myelination of small- diameter axons in the central nervous system (CNS) (PubMed:26188006). Promotes activation of focal adhesion kinase. May function as a cellular signal transducer (By similarity). {ECO:0000250|UniProtKB:Q3UHK6, ECO:0000269|PubMed:26188006}.;
Disease: DISEASE: Tremor, hereditary essential 5 (ETM5) [MIM:616736]: A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. {ECO:0000269|PubMed:26188006}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: -1.7
RVIS percentile EVS: 2.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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