TENM3

Chr 4AR

teneurin transmembrane protein 3

Also known as: MCOPCB9, MCOPS15, ODZ3, TEN3, TNM3, Ten-m3, ten-3

NCBI Gene: 55714 ENSG00000218336 UniProt: Q9P273 OMIM: 610083

This gene encodes a teneurin transmembrane protein that regulates neural connectivity establishment, controls precise topographic projections in the hippocampus, and is required for proper dendrite morphogenesis and axon targeting in the visual system. Autosomal recessive mutations cause syndromic microphthalmia with or without coloboma, sometimes associated with developmental dysplasia of the hip. The gene is highly constrained against loss-of-function variants (pLI >0.99), indicating that heterozygous loss-of-function is likely not tolerated.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.262 OMIM phenotypes

Clinical Summary— TENM3

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.26LOEUF

pLI 1.000

Z-score 8.11

OE 0.18 (0.13–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.30Z-score

OE missense 0.76 (0.73–0.80)

1191 obs / 1557.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.18 (0.13–0.26)

0≤0.351.4

Missense OE?0.76 (0.73–0.80)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 21 / 114.7Missense obs/exp: 1191 / 1557.4Syn Z: 0.11

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTENM3-related colobomatous microphthalmiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.3097th %ile

GOF

0.3887th %ile

LOF

0.73top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.