TEKT3

Chr 17AR

tektin 3

Also known as: SPGF81

NCBI Gene: 64518 ENSG00000125409 UniProt: Q9BXF9 OMIM: 612683

The protein forms filamentous polymers that are incorporated into ciliary and flagellar microtubules and is required for normal sperm motility. Mutations cause spermatogenic failure with autosomal recessive inheritance. This gene shows very low constraint against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene product belongs to the tektin family of proteins. Tektins comprise a family of filament-forming proteins that are coassembled with tubulins to form ciliary and flagellar microtubules. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.461 OMIM phenotype

Clinical Summary— TEKT3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 104 VUS of 113 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.46LOEUF

pLI 0.000

Z-score -0.21

OE 1.05 (0.76–1.46)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.20Z-score

OE missense 0.97 (0.88–1.07)

289 obs / 298.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.05 (0.76–1.46)

0≤0.351.4

Missense OE?0.97 (0.88–1.07)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 25 / 23.9Missense obs/exp: 289 / 298.9Syn Z: 0.73

This gene — mechanism propensity

0.77top 25%

GOF

0.7029th %ile

LOF

0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic1

VUS104

Likely Benign1

Benign1

Pathogenic

Likely Pathogenic

104

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	1	2	3
Likely Pathogenic	1	0	1
VUS	0	104	104
Likely Benign	0	1	1
Benign	1	0	1
Total	3	107	110

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

124 pathogenic / likely-pathogenic (of 131) ClinVar copy-number / structural variants overlap TEKT3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →