FANCL

FA complementation group L, the group of PHD finger proteins|FA core complex|FA complementation groups

Basic information

Region (hg38): 2:58159242-58241410

Previous symbols: [ "PHF9" ]

Links

ENSG00000115392 ∙ NCBI:55120 ∙ OMIM:608111 ∙ HGNC:20748 ∙ Uniprot:Q9NW38 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia, complementation group L	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	12973351; 20301575; 22720145; 25754594

ClinVar

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

• Fanconi anemia (464 variants)
• Fanconi anemia complementation group L (139 variants)
• not provided (77 variants)
• not specified (38 variants)
• Inborn genetic diseases (16 variants)
• Fanconi anemia complementation group A (6 variants)
• FANCL-related condition (3 variants)
• VATER association (1 variants)
• Premature ovarian insufficiency (1 variants)
• VACTERL association, X-linked, with or without hydrocephalus (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FANCL gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	78	2	83
missense			197	6	1	204
nonsense	10	14				24
start loss	1	4				5
frameshift	16	15	3			34
inframe indel			3		1	4
splice donor/acceptor (+/-2bp)		14				14
splice region	1		16	27	1	45
non coding			27	93	34	154
Total	27	47	233	177	38

Highest pathogenic variant AF is 0.0000394

Variants in FANCL

This is a list of pathogenic ClinVar variants found in the FANCL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-58159250-T-G		Fanconi anemia complementation group L	Uncertain significance (Jan 13, 2018)
2-58159314-TAACA-T		Fanconi anemia	Uncertain significance (Jun 14, 2016)
2-58159331-T-C		Fanconi anemia complementation group L	Uncertain significance (Apr 27, 2017)
2-58159380-A-T		not specified	Uncertain significance (Sep 22, 2023)
2-58159419-A-C		not specified	Uncertain significance (Jun 10, 2022)
2-58159432-T-C		Fanconi anemia complementation group L	Likely benign (Jan 12, 2018)
2-58159445-A-G		not specified	Uncertain significance (Jul 19, 2022)
2-58159458-A-C		not specified	Uncertain significance (Apr 17, 2023)
2-58159469-G-A		Fanconi anemia complementation group L • not specified	Uncertain significance (Jan 26, 2023)
2-58159484-G-C		Fanconi anemia complementation group L	Uncertain significance (Jan 13, 2018)
2-58159600-T-C		Fanconi anemia complementation group L	Uncertain significance (Jan 12, 2018)
2-58159600-T-G		Fanconi anemia complementation group L	Uncertain significance (Jan 15, 2018)
2-58159637-C-T		Fanconi anemia complementation group L	Uncertain significance (Jan 13, 2018)
2-58159659-T-TGATG		not specified	Uncertain significance (Mar 14, 2023)
2-58159670-T-C		Fanconi anemia complementation group L	Benign/Likely benign (Jun 10, 2019)
2-58159676-G-A		Fanconi anemia complementation group L	Uncertain significance (Jan 13, 2018)
2-58159681-A-T		not specified	Uncertain significance (Sep 22, 2022)
2-58159769-T-G		Fanconi anemia	Likely benign (Nov 24, 2023)
2-58159770-G-C		Fanconi anemia	Uncertain significance (May 04, 2022)
2-58159772-T-C		Fanconi anemia	Uncertain significance (Oct 07, 2022)
2-58159775-C-G		Fanconi anemia	Uncertain significance (Aug 16, 2022)
2-58159778-C-G		Fanconi anemia • not specified • Fanconi anemia complementation group L	Likely benign (Jan 31, 2024)
2-58159784-A-G		Fanconi anemia	Uncertain significance (Aug 26, 2021)
2-58159784-AT-A			Uncertain significance (Jul 01, 2022)
2-58159793-G-GTAAT		not specified • Fanconi anemia • Fanconi anemia complementation group A • Fanconi anemia complementation group L • FANCL-related disorder	Conflicting classifications of pathogenicity (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FANCL	protein_coding	protein_coding	ENST00000402135	14	82130

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.94e-23	0.000106	125654	0	94	125748	0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.31	251	199	1.26	0.00000943	2494
Missense in Polyphen		40	46.181	0.86616		582
Synonymous	-0.598	73	66.8	1.09	0.00000323	684
Loss of Function	-0.934	31	25.9	1.20	0.00000117	318

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00119	0.00119
Ashkenazi Jewish	0.000496	0.000496
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000344	0.000343
Middle Eastern	0.000164	0.000163
South Asian	0.000425	0.000425
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ubiquitin ligase protein that mediates monoubiquitination of FANCD2 in the presence of UBE2T, a key step in the DNA damage pathway (PubMed:12973351, PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:24389026). Also mediates monoubiquitination of FANCI (PubMed:19589784). May stimulate the ubiquitin release from UBE2W. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth. {ECO:0000269|PubMed:12973351, ECO:0000269|PubMed:16916645, ECO:0000269|PubMed:17938197, ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784, ECO:0000269|PubMed:24389026}.
• Disease: DISEASE: Fanconi anemia complementation group L (FANCL) [MIM:614083]: 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:12973351}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Fanconi Anemia Pathway;DNA Repair;Fanconi anemia pathway;BARD1 signaling events (Consensus)

Recessive Scores

• pRec: 0.284

Intolerance Scores

• loftool: 0.985
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• pHI: 0.324
• hipred: N
• hipred_score: 0.449
• ghis: 0.625

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.875

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fancl
• Phenotype: endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; embryo phenotype; pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; vision/eye phenotype; skeleton phenotype

Gene ontology

• Biological process: DNA repair;protein monoubiquitination;cellular response to DNA damage stimulus;gamete generation;interstrand cross-link repair;regulation of cell population proliferation
• Cellular component: nuclear envelope;nucleoplasm;cytoplasm;nuclear body;intracellular membrane-bounded organelle;Fanconi anaemia nuclear complex
• Molecular function: ubiquitin-protein transferase activity;protein binding;ubiquitin protein ligase binding;metal ion binding;ubiquitin protein ligase activity