FANCA

Chr 16AR

FA complementation group A

Also known as: FA, FA-H, FA1, FAA, FACA, FAH, FANCH

NCBI Gene: 2175 ENSG00000187741 UniProt: O15360

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 A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group AMIM #227650

Active trials

Pathogenic / LP

450

ClinVar variants

Pubs (1 yr)

-5.4

Missense Z

1.37

LOEUF

Clinical Summary— FANCA

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Gene-Disease Validity (ClinGen)

Fanconi anemia complementation group A · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

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

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ClinVar Variants

18 Pathogenic / Likely Pathogenic· 316 VUS of 450 total submissions

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Clinical Trials

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

📖

GeneReview available — FANCA

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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.37LOEUF

pLI 0.000

Z-score -1.29

OE 1.15 (0.98–1.37)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-5.41Z-score

OE missense 1.55 (1.47–1.62)

1202 obs / 777.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.15 (0.98–1.37)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.55 (1.47–1.62)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.57

0≤1.21.6

LoF obs/exp: 96 / 83.3Missense obs/exp: 1202 / 777.3Syn Z: -8.03

ClinVar Variant Classifications

450 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12

Likely Pathogenic6

VUS316

Likely Benign115

Conflicting1

Pathogenic

Likely Pathogenic

316

VUS

115

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	0	4	0	12
Likely Pathogenic	4	1	1	0	6
VUS	2	272	25	17	316
Likely Benign	0	7	41	67	115
Benign	0	0	0	0	0
Conflicting	—				1
Total	14	280	71	84	450

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

View in ClinVar →

Protein Context — Lollipop Plot

FANCA · protein map & ClinVar variants

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

Gene2Phenotype Curations

FANCA-related Fanconi anemia

definitive

ARLoss Of FunctionAbsent Gene Product

Dev. DisordersSkinSkeletal

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

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

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GeneReview available — FANCA

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING

NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21

NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

Fanconi Anemia Complementation Group A

Gene Therapy for Fanconi Anemia, Complementation Group A

ACTIVE NOT RECRUITING

NCT04248439Phase PHASE2Rocket Pharmaceuticals Inc.Started 2020-07-15

RP-L102

NSCLCNon Small Cell Lung Cancer

Pre-operative Tumor Treating Fields in Patients With Resectable Lung Cancer

NOT YET RECRUITING

NCT06552000Phase NAUniversity of Texas Southwestern Medical CenterStarted 2026-07-01

NovoTTF-200T System

Acute LeukemiaAdenomatous PolyposisAdrenocortical Carcinoma

Familial Investigations of Childhood Cancer Predisposition

RECRUITING

NCT03050268St. Jude Children's Research HospitalStarted 2017-04-06

Gastric CancerGastroEsophageal Cancer

Study of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers

ACTIVE NOT RECRUITING

NCT05379972Phase PHASE2University of Colorado, DenverStarted 2023-01-12

PembrolizumabOlaparibStereotactic Body Radiation Therapy

Bone Marrow Failure DisordersVEXAS SyndromeHemoglobinurea, Paroxysmal

Molecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study

ENROLLING BY INVITATION

NCT07102849National Heart, Lung, and Blood Institute (NHLBI)Started 2025-09-09

Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING

NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01

ST-01156

Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

RECRUITING

NCT02693535Phase PHASE2American Society of Clinical OncologyStarted 2016-03-14

PalbociclibSunitinibTemsirolimus

Prostate Cancer Metastatic Castration-ResistantAbnormal DNA RepairMetastatic Prostate Carcinoma

Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects

ACTIVE NOT RECRUITING

NCT03012321Phase PHASE2Northwestern UniversityStarted 2017-01-12

OlaparibAbiraterone AcetatePrednisone

Fanconi Anemia Complementation Group AFanconi Anemia

Long-Term Follow-up of Subjects With Fanconi Anaemia Subtype A Treated With ex Vivo Gene Therapy

ENROLLING BY INVITATION

NCT04437771Rocket Pharmaceuticals Inc.Started 2020-06-01

Safety and efficacy assessments

Metastatic Breast CancerInvasive Breast CancerSomatic Mutation Breast Cancer (BRCA1)

Olaparib In Metastatic Breast Cancer

ACTIVE NOT RECRUITING

NCT03344965Phase PHASE2Beth Israel Deaconess Medical CenterStarted 2018-04-01