FANCG

Chr 9AR

FA complementation group G

Also known as: FAG, XRCC9

NCBI Gene: 2189 ENSG00000221829 UniProt: O15287 OMIM: 602956

The FANCG 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 G, a disorder characterized by bone marrow failure, congenital anomalies, cytogenetic instability, and increased cancer predisposition. This gene follows autosomal recessive inheritance and is highly intolerant to loss-of-function variants.

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 G. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group GMIM #614082

UniProtFanconi anemia complementation group G

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Fanconi anemia complementation group G · AR · ClinGen 2019

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.09

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.09LOEUF

pLI 0.000

Z-score 1.15

OE 0.78 (0.57–1.09)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.96 (0.87–1.06)

301 obs / 313.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.57–1.09)

0≤0.351.4

Missense OE?0.96 (0.87–1.06)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 25 / 32.0Missense obs/exp: 301 / 313.2Syn Z: 0.01

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

693 rare PASS variants

Rare truncating (LoF)

1 in 620

160 rare PASS variants

Rare synonymous (reference)

1 in 200

321 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FANCG. 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 120	1 in 560
South Asian	~43k	1 in 80	1 in 610
Remaining (unassigned)	~30k	1 in 89	1 in 500
European (Finnish)	~27k	1 in 180	1 in 890
Admixed American	~22k	1 in 87	1 in 1,200
African / African American	~21k	1 in 110	1 in 620
East Asian	~20k	1 in 67	1 in 370
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 80	≈ 1 in 960

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 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓