IFFO1

Chr 12

intermediate filament family orphan 1

Also known as: HOM-TES-103, IFFO

NCBI Gene: 25900ENSG00000010295UniProt: Q0D2I5

This intermediate filament protein functions as a nuclear matrix component that immobilizes broken DNA ends and suppresses chromosome translocations during DNA double-strand break repair by scaffolding DNA repair proteins. The gene is highly constrained against loss-of-function variants (LOEUF 0.695), but no established human disease associations have been reported in the provided data.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
44
P/LP submissions
0%
P/LP missense
0.69
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— IFFO1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 99 VUS of 154 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
0.69LOEUF
pLI 0.000
Z-score 2.75
OE 0.42 (0.26–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.97Z-score
OE missense 0.85 (0.77–0.94)
291 obs / 341.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.26–0.69)
0≤0.351.4
Missense OE0.85 (0.77–0.94)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 11 / 26.2Missense obs/exp: 291 / 341.7Syn Z: 0.66
DN
0.78top 25%
GOF
0.76top 25%
LOF
0.3455th %ile

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

DNprediction above median
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.

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS99
Likely Benign1
42
Pathogenic
2
Likely Pathogenic
99
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
0
2
0
2
VUS
0
90
9
0
99
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total090531144

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

View in ClinVar →

Protein Context — Lollipop Plot

IFFO1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients