ODF4

Chr 17

outer dense fiber of sperm tails 4

Also known as: CT134, CT136, OPPO1

The protein is a component of the outer dense fibers in sperm tails and is involved in sperm tail structure and movement. Mutations cause autosomal recessive primary ciliary dyskinesia with reduced sperm motility, affecting the respiratory system through ciliary dysfunction and male fertility through impaired sperm function. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.21
Clinical SummaryODF4
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.21LOEUF
pLI 0.011
Z-score 1.19
OE 0.53 (0.261.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.93Z-score
OE missense 0.78 (0.670.91)
110 obs / 141.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.261.21)
00.351.4
Missense OE0.78 (0.670.91)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 4 / 7.5Missense obs/exp: 110 / 141.0Syn Z: 0.79
DN
0.6648th %ile
GOF
0.76top 25%
LOF
0.3551th %ile

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

GOFprediction above median
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ODF4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗