ODF4

Chr 17

outer dense fiber of sperm tails 4

Also known as: CT134, CT136, OPPO1

NCBI Gene: 146852 ENSG00000184650 UniProt: Q2M2E3 OMIM: 610097

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is localized in the outer dense fibers of the tails of mature sperm. This protein is thought to have some important role in the sperm tail. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.21

Clinical Summary— ODF4

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

31 VUS of 32 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?

1.21LOEUF

pLI 0.011

Z-score 1.19

OE 0.53 (0.26–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.93Z-score

OE missense 0.78 (0.67–0.91)

110 obs / 141.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.26–1.21)

0≤0.351.4

Missense OE?0.78 (0.67–0.91)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 4 / 7.5Missense obs/exp: 110 / 141.0Syn Z: 0.79

This gene — mechanism propensity

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

32 submitted variants in ClinVar

ClinVar

Classification Summary

VUS31

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	31	31
Likely Benign	1	1
Benign	0	0
Total	32	32

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap ODF4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →