DNALI1

Chr 1AR

dynein axonemal light intermediate chain 1

ENSG00000163879 UniProt: O14645 OMIM: 602135

This gene encodes a protein involved in sperm flagellum assembly and is a candidate gene for primary ciliary dyskinesia based on its homology to Chlamydomonas inner dynein arm components. Mutations cause spermatogenic failure with autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants (very low pLI score), which is consistent with its recessive disease pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in sperm flagellum assembly

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.511 OMIM phenotype

Clinical Summary— DNALI1

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.51LOEUF

pLI 0.000

Z-score 0.01

OE 1.00 (0.68–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.02Z-score

OE missense 1.00 (0.88–1.13)

168 obs / 168.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.00 (0.68–1.51)

0≤0.351.4

Missense OE?1.00 (0.88–1.13)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 16 / 16.0Missense obs/exp: 168 / 168.6Syn Z: -0.65

This gene — mechanism propensity

0.76top 25%

GOF

0.3491th %ile

LOF

0.4528th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.