FANCF

Chr 11AR

FA complementation group F

Also known as: FAF

NCBI Gene: 2188 ENSG00000183161 UniProt: Q9NPI8 OMIM: 613897

This protein functions in DNA repair, specifically in interstrand DNA cross-link repair and maintenance of chromosome stability as part of the Fanconi anemia nuclear protein complex. Mutations cause Fanconi anemia complementation group F, characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The condition follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group F. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group FMIM #603467

UniProtFanconi anemia complementation group F

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Fanconi anemia complementation group F · AR · ClinGen 2021

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.52

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — FANCF

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.52LOEUF

pLI 0.459

Z-score 1.16

OE 0.00 (0.00–1.52)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.83Z-score

OE missense 1.38 (1.24–1.53)

257 obs / 186.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.52)

0≤0.351.4

Missense OE?1.38 (1.24–1.53)

0≤0.61.4

Synonymous OE?1.43

0≤1.21.6

LoF obs/exp: 0 / 1.6Missense obs/exp: 257 / 186.8Syn Z: -3.08

Background carrier burden — how many people carry a rare variant somewhere in FANCF?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

584 rare PASS variants

Rare truncating (LoF)

1 in 1,100

66 rare PASS variants

Rare synonymous (reference)

1 in 160

275 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FANCF. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,100
South Asian	~43k	1 in 76	1 in 1,500
Remaining (unassigned)	~30k	1 in 74	1 in 1,100
European (Finnish)	~27k	1 in 430	≈ 1 in 27,000
Admixed American	~22k	1 in 83	1 in 1,400
African / African American	~21k	1 in 65	1 in 940
East Asian	~20k	1 in 290	1 in 1,800
Ashkenazi Jewish	~13k	1 in 200	none seen
Middle Eastern	~2,884	1 in 100	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓