FAN1

Chr 15AR

FANCD2 and FANCI associated nuclease 1

Also known as: KIAA1018, KMIN, MTMR15, hFAN1

The protein functions as a nuclease that repairs DNA interstrand cross-links through 5' flap endonuclease and 5'-3' exonuclease activity, specifically resolving homologous recombination intermediates at sites of DNA damage. Mutations cause karyomegalic interstitial nephritis, a kidney disease characterized by enlarged nuclei in renal tubular cells, inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants (LOEUF 1.117), reflecting its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 1.121 OMIM phenotype
Clinical SummaryFAN1
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Gene-Disease Validity (ClinGen)
hereditary nonpolyposis colon cancer · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
123 unique Pathogenic / Likely Pathogenic· 289 VUS of 561 total submissions
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GeneReview available — FAN1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.12LOEUF
pLI 0.000
Z-score 0.88
OE 0.86 (0.671.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.05Z-score
OE missense 1.01 (0.941.08)
571 obs / 567.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.671.12)
00.351.4
Missense OE1.01 (0.941.08)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 42 / 48.6Missense obs/exp: 571 / 567.8Syn Z: -0.89

ClinVar Variant Classifications

561 submitted variants in ClinVar

Classification Summary

Pathogenic89
Likely Pathogenic34
VUS289
Likely Benign78
Benign45
Conflicting9
89
Pathogenic
34
Likely Pathogenic
289
VUS
78
Likely Benign
45
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
72
0
89
Likely Pathogenic
33
1
0
0
34
VUS
1
241
43
4
289
Likely Benign
0
6
27
45
78
Benign
1
1
41
2
45
Conflicting
9
Total5125018351544

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

View in ClinVar →

Protein Context — Lollipop Plot

FAN1 · 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 →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC