ODF1

Chr 8

outer dense fiber of sperm tails 1

Also known as: CT133, HSPB10, ODF, ODF27, ODFP, ODFPG, ODFPGA, ODFPGB

NCBI Gene: 4956 ENSG00000155087 UniProt: Q14990 OMIM: 182878

The ODF1 protein is the main component of outer dense fibers, cytoskeletal structures that surround the sperm tail axoneme and maintain elastic structure while protecting against shear forces during sperm transport. Mutations cause abnormal sperm morphology and male infertility with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, suggesting complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

The outer dense fibers are cytoskeletal structures that surround the axoneme in the middle piece and principal piece of the sperm tail. The fibers function in maintaining the elastic structure and recoil of the sperm tail as well as in protecting the tail from shear forces during epididymal transport and ejaculation. Defects in the outer dense fibers lead to abnormal sperm morphology and infertility. The human outer dense fibers contains at least 10 major proteins and this gene encodes the main protein. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.27

Clinical Summary— ODF1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

30 VUS of 33 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.27LOEUF

pLI 0.972

Z-score 3.08

OE 0.00 (0.00–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.68Z-score

OE missense 0.84 (0.73–0.98)

123 obs / 146.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.27)

0≤0.351.4

Missense OE?0.84 (0.73–0.98)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 0 / 11.0Missense obs/exp: 123 / 146.1Syn Z: 0.44

This gene — mechanism propensity

0.5673th %ile

GOF

0.7029th %ile

LOF

0.60top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.27

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

33 submitted variants in ClinVar

ClinVar

Classification Summary

VUS30

Benign3

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	30	0	30
Likely Benign	0	0	0	0
Benign	2	0	1	3
Total	2	30	1	33

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap ODF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →