FANCA

FA complementation group A, the group of FA core complex|FA complementation groups

Basic information

Region (hg38): 16:89726683-89816977

Previous symbols: [ "FACA", "FANCH" ]

Links

ENSG00000187741 ∙ NCBI:2175 ∙ OMIM:607139 ∙ HGNC:3582 ∙ Uniprot:O15360 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fanconi anemia complementation group A (Definitive), mode of inheritance: AR
• Fanconi anemia complementation group A (Definitive), mode of inheritance: AR
• Fanconi anemia complementation group A (Definitive), mode of inheritance: AR
• Fanconi anemia complementation group A (Strong), mode of inheritance: AR
• Fanconi anemia (Supportive), mode of inheritance: AR
• Fanconi anemia complementation group A (Strong), mode of inheritance: AR
• Fanconi anemia complementation group A (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia, complementation group A	AR	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	13826667; 6338978; 2571931; 1536187; 1521091; 8502512; 8081006; 8781414; 9371798; 10094191; 11389461; 14504102; 14605744; 17105750; 20301575; 20507306; 21273304; 22480464; 22950077; 23067021; 23898106; 23973728

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FANCA gene.

• Fanconi_anemia (4346 variants)
• Inborn_genetic_diseases (2232 variants)
• Fanconi_anemia_complementation_group_A (1557 variants)
• not_provided (860 variants)
• not_specified (250 variants)
• FANCA-related_disorder (201 variants)
• Ovarian_cancer (10 variants)
• Hereditary_cancer-predisposing_syndrome (5 variants)
• See_cases (4 variants)
• Neuroblastoma (2 variants)
• Microcephaly (2 variants)
• Diffuse_pediatric-type_high-grade_glioma,_H3-wildtype_and_IDH-wildtype (2 variants)
• Abnormality_of_blood_and_blood-forming_tissues (2 variants)
• Pituitary_stalk_interruption_syndrome (1 variants)
• Premature_ovarian_failure (1 variants)
• Pediatric_high-grade_glioma (1 variants)
• Neurodevelopmental_abnormality (1 variants)
• Hepatoblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FANCA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000135.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	5	2	44	1284	6	1341
missense	32	74	2323	213	5	2647
nonsense	135	94	5			234
start loss	3	7				10
frameshift	215	138	10			363
splice donor/acceptor (+/-2bp)	78	164	18	1		261
Total	468	479	2400	1498	11

Highest pathogenic variant AF is 0.00012729385

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FANCA	protein_coding	protein_coding	ENST00000389301	43	79109

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125478	0	270	125748	0.00107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-5.41	1202	777	1.55	0.0000482	9398
Missense in Polyphen		41	31.281	1.3107		289
Synonymous	-8.03	506	322	1.57	0.0000218	2907
Loss of Function	-1.29	96	83.3	1.15	0.00000424	952

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00240	0.00240
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00148	0.00147
Finnish	0.000185	0.000185
European (Non-Finnish)	0.00126	0.00126
Middle Eastern	0.00148	0.00147
South Asian	0.00114	0.00114
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be involved in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability.
• Disease: DISEASE: Fanconi anemia, complementation group A (FANCA) [MIM:227650]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:10094191, ECO:0000269|PubMed:10210316, ECO:0000269|PubMed:10521298, ECO:0000269|PubMed:10807541, ECO:0000269|PubMed:11091222, ECO:0000269|PubMed:17924555, ECO:0000269|PubMed:9371798, ECO:0000269|PubMed:9399890, ECO:0000269|PubMed:9929978}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Fanconi Anemia Pathway;DNA Repair;role of brca1 brca2 and atr in cancer susceptibility;brca1 dependent ub ligase activity;Fanconi anemia pathway;BARD1 signaling events (Consensus)

Recessive Scores

• pRec: 0.243

Intolerance Scores

• loftool: 0.0821
• rvis_EVS: -0.1
• rvis_percentile_EVS: 45.67

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: DNA repair;male meiotic nuclear division;male gonad development;female gonad development;interstrand cross-link repair;regulation of cell population proliferation;regulation of regulatory T cell differentiation;regulation of inflammatory response;regulation of DNA-binding transcription factor activity;protein-containing complex assembly;regulation of CD40 signaling pathway
• Cellular component: nucleus;nucleoplasm;cytoplasm;Fanconi anaemia nuclear complex
• Molecular function: protein binding