TEKT1

Chr 17

tektin 1

NCBI Gene: 83659 ENSG00000167858 UniProt: Q969V4

This protein forms filamentous polymers in the walls of ciliary and flagellar microtubules and is a component of dynein-decorated doublet microtubules in cilia and flagellar axonemes. Mutations in TEKT1 cause male infertility due to multiple morphological abnormalities of the flagella, inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variants, consistent with its specialized role in male fertility rather than essential cellular functions.

ResearchSummary from RefSeq, 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. This gene is predominantly expressed in the testis and in mouse, tektin 1 mRNA was localized to the spermatocytes and round spermatids in the seminiferous tubules, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.08

Clinical Summary— TEKT1

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Gene-Disease Validity (ClinGen)

primary ciliary dyskinesia · ARDisputed

Disputed — evidence questions this relationship

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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

72 VUS of 80 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.30

OE 0.67 (0.43–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.88–1.09)

235 obs / 240.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.43–1.08)

0≤0.351.4

Missense OE?0.98 (0.88–1.09)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 12 / 17.9Missense obs/exp: 235 / 240.8Syn Z: 0.25

This gene — mechanism propensity

0.81top 10%

GOF

0.81top 10%

LOF

0.1797th %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

80 submitted variants in ClinVar

ClinVar

Classification Summary

VUS72

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	72	0	72
Likely Benign	3	1	4
Benign	0	0	0
Total	75	1	76

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap TEKT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →