FANCE

Chr 6AR

FA complementation group E

Also known as: FACE, FAE

NCBI Gene: 2178 ENSG00000112039 UniProt: Q9HB96 OMIM: 613976

The FANCE protein functions as part of the Fanconi anemia complex in DNA cross-link repair and is required for nuclear accumulation of FANCC, providing a critical bridge between the FA complex and FANCD2. Mutations cause Fanconi anemia complementation group E, an autosomal recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The gene is highly intolerant to loss-of-function variants (pLI nearly 1.0), reflecting the critical nature of this DNA repair pathway.

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 E. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.892 OMIM phenotypes

Clinical Summary— FANCE

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Gene-Disease Validity (ClinGen)

Fanconi anemia complementation group E · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

80 unique Pathogenic / Likely Pathogenic· 372 VUS of 851 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — FANCE

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 1.96

OE 0.56 (0.36–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.88–1.09)

238 obs / 243.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.36–0.89)

0≤0.351.4

Missense OE?0.98 (0.88–1.09)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 13 / 23.2Missense obs/exp: 238 / 243.7Syn Z: 0.12

ClinVar Variant Classifications

851 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27

Likely Pathogenic53

VUS372

Likely Benign317

Benign21

Conflicting46

Pathogenic

Likely Pathogenic

372

VUS

317

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	26	0	1	0	27
Likely Pathogenic	49	1	3	0	53
VUS	6	321	40	5	372
Likely Benign	0	7	118	192	317
Benign	0	4	15	2	21
Conflicting	—				46
Total	81	333	177	199	836

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap FANCE — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →