FCGR3A

Fc gamma receptor IIIa, the group of Fc receptors|Immunoglobulin like domain containing|CD molecules

Basic information

Region (hg38): 1:161541758-161550968

Previous symbols: [ "FCGR3", "FCG3" ]

Links

ENSG00000203747 ∙ NCBI:2214 ∙ OMIM:146740 ∙ HGNC:3619 ∙ Uniprot:P08637 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 20	AR	Allergy/Immunology/Infectious	Individuals have been described as affected by early-onset severe herpes viral infections (eg, EBV, HPV), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	8608639; 8874200; 23006327

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FCGR3A gene.

• Inborn genetic diseases (16 variants)
• not specified (7 variants)
• Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity (4 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FCGR3A 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			1		1	2
missense			15	2	3	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2	1	1	4
Total	0	0	18	3	5

Variants in FCGR3A

This is a list of pathogenic ClinVar variants found in the FCGR3A region.

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

Position	Type	Phenotype	Significance	ClinVar
1-161543076-C-A		not specified	Uncertain significance (May 30, 2023)
1-161543152-C-G		not specified	Uncertain significance (May 04, 2023)
1-161543166-G-A		not specified	Uncertain significance (Aug 02, 2022)
1-161543188-A-G		not specified	Likely benign (Apr 07, 2023)
1-161544752-A-C		not specified	Benign/Likely benign (Jan 24, 2024)
1-161544763-C-A		not specified	Uncertain significance (Nov 18, 2022)
1-161544784-T-C		not specified	Uncertain significance (Sep 23, 2023)
1-161544882-C-A		not specified	Uncertain significance (Apr 20, 2023)
1-161544922-T-A		not specified	Uncertain significance (Jul 26, 2022)
1-161544928-A-G		not specified	Uncertain significance (Sep 20, 2023)
1-161548424-T-C		not specified	Benign (Jan 24, 2024)
1-161548442-C-T		not specified	Uncertain significance (Sep 17, 2021)
1-161548502-T-C		not specified	Uncertain significance (Mar 28, 2022)
1-161548524-C-T		not specified	Benign (Mar 28, 2016)
1-161548543-A-C		not specified	Benign (Apr 19, 2019)
1-161548543-A-T		Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity • not specified	Uncertain significance (Mar 30, 2021)
1-161548546-C-T		not specified	Benign (Mar 28, 2016)
1-161548595-C-T		Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity	Uncertain significance (Apr 19, 2018)
1-161548602-C-A		not specified	Uncertain significance (May 17, 2023)
1-161548619-C-A		not specified	Uncertain significance (Oct 06, 2022)
1-161548620-C-A		not specified	Uncertain significance (Oct 06, 2022)
1-161548644-A-G		Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity	Uncertain significance (Mar 30, 2021)
1-161549028-G-A		not specified	Uncertain significance (Jan 16, 2024)
1-161549621-C-A		not specified	Benign (Jan 24, 2024)
1-161549705-A-T		not specified	Uncertain significance (Apr 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FCGR3A	protein_coding	protein_coding	ENST00000367969	5	89369

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000370	0.374	125701	0	47	125748	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.04	186	150	1.24	0.00000765	1850
Missense in Polyphen		52	44.001	1.1818		614
Synonymous	0.262	56	58.6	0.956	0.00000295	555
Loss of Function	0.407	9	10.4	0.864	4.45e-7	121

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000272	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000274	0.000273
Middle Eastern	0.000218	0.000217
South Asian	0.0000659	0.0000653
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis. {ECO:0000269|PubMed:21768335, ECO:0000269|PubMed:22023369}.
• Disease: DISEASE: Immunodeficiency 20 (IMD20) [MIM:615707]: A rare autosomal recessive primary immunodeficiency characterized by functional deficiency of NK cells. Affected individuals typically present with severe herpes viral infections, particularly Epstein Barr virus (EBV), and human papillomavirus (HPV). {ECO:0000269|PubMed:23006327, ECO:0000269|PubMed:8608639, ECO:0000269|PubMed:8609432, ECO:0000269|PubMed:8874200}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Phagosome - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Human Complement System;ras-independent pathway in nk cell-mediated cytotoxicity;FCGR activation;Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Regulation of actin dynamics for phagocytic cup formation (Consensus)

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.990
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.8

Haploinsufficiency Scores

• pHI: 0.0179
• hipred: N
• hipred_score: 0.139
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.00307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fcgr4
• Phenotype: homeostasis/metabolism phenotype; skeleton phenotype; hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: immune response;Fc-gamma receptor signaling pathway involved in phagocytosis;regulation of immune response
• Cellular component: plasma membrane;external side of plasma membrane;integral component of membrane;extracellular exosome
• Molecular function: IgG binding