DNALI1

Chr 1AR

dynein axonemal light intermediate chain 1

Also known as: P28, SPGF83, dJ423B22.5, hp28

NCBI Gene: 7802ENSG00000163879UniProt: O14645

This gene is the human homolog of the Chlamydomonas inner dynein arm gene, p28. The precise function of this gene is not known, however, it is a potential candidate for immotile cilia syndrome (ICS). Ultrastructural defects of the inner dynein arms are seen in patients with ICS. Immotile mutant strains of Chlamydomonas, a biflagellated algae, exhibit similar defects. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spermatogenic failure 83MIM #620354
AR
79
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNALI1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 56 VUS of 79 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.02Z-score
OE missense 1.00 (0.88–1.13)
168 obs / 168.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.00 (0.68–1.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.88–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 16 / 16.0Missense obs/exp: 168 / 168.6Syn Z: -0.65

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS56
Likely Benign4
Benign5
6
Pathogenic
1
Likely Pathogenic
56
VUS
4
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
5
0
6
Likely Pathogenic
0
0
1
0
1
VUS
0
44
12
0
56
Likely Benign
0
1
3
0
4
Benign
0
1
1
3
5
Total14622372

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

View in ClinVar →

Protein Context — Lollipop Plot

DNALI1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spermatogenic failure 83

MIM #620354

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice.
Yang M et al.·Elife
2025
Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice.
Wang R et al.·Front Med
2023
Novel axonemal protein ZMYND12 interacts with TTC29 and DNAH1, and is required for male fertility and flagellum function.
Dacheux D et al.·Elife
2023
DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice.
Wang X et al.·Elife
2024
Homozygous mutation in DNALI1 leads to asthenoteratozoospermia by affecting the inner dynein arms.
Sha Y et al.·Front Endocrinol (Lausanne)
2023
DNALI1 Promotes Neurodegeneration after Traumatic Brain Injury via Inhibition of Autophagosome-Lysosome Fusion.
Ding X et al.·Adv Sci (Weinh)
2024
Splicing Mutation in DNALI1 Causes Male Infertility with Severe Oligoasthenoteratozoospermia in Humans.
Zhang F et al.·Reprod Sci
2024Case report
Functional analysis of the 1p34.3 risk locus implicates GNL2 in high-grade serous ovarian cancer.
Nakamura K et al.·Am J Hum Genet
2022Functional
Exploring nasopharyngeal carcinoma genetics: Bioinformatics insights into pathways and gene associations.
Che Ismail CL et al.·Med J Malaysia
2024Review
Dysregulation of sputum columnar epithelial cells and products in distinct asthma phenotypes.
Qin L et al.·Clin Exp Allergy
2019Clinical trial
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools