FCHO1

FCH and mu domain containing endocytic adaptor 1, the group of F-BAR domain containing

Basic information

Region (hg38): 19:17747717-17788568

Links

ENSG00000130475 ∙ NCBI:23149 ∙ OMIM:613437 ∙ HGNC:29002 ∙ Uniprot:O14526 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 76 (Definitive), mode of inheritance: AR
• immunodeficiency 76 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 76	AR	Allergy/Immunology/Infectious; Oncologic	Individuals have been described as affected by early-onset and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Oncologic complications have been described, and awareness may alow early diagnosis and management; HSCT has been described	Allergy/Immunology/Infectious; Oncologic	30822429; 32098969

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FCHO1 gene.

• not provided (499 variants)
• Inborn genetic diseases (37 variants)
• not specified (21 variants)
• Immunodeficiency 76 (2 variants)
• FCHO1-related condition (1 variants)
• Immunodeficiency with T and B cell lymphopenia (1 variants)
• Severe congenital neutropenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FCHO1 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			5	106	11	122
missense			229	12	6	247
nonsense	1	1				2
start loss						0
frameshift	3		1			4
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			12	26	3	41
non coding			4	84	28	116
Total	4	2	240	202	45

Highest pathogenic variant AF is 0.0000131

Variants in FCHO1

This is a list of pathogenic ClinVar variants found in the FCHO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-17755170-G-T			Likely benign (Jul 26, 2023)
19-17755179-G-C			Benign (Jan 29, 2024)
19-17755192-G-A		Immunodeficiency 76	Pathogenic (Feb 10, 2021)
19-17755200-C-T			Likely benign (Jul 19, 2022)
19-17755203-T-G			Likely benign (Oct 27, 2023)
19-17755208-T-C			Likely benign (Jul 11, 2022)
19-17762730-C-T			Likely benign (Jan 01, 2023)
19-17762758-G-T			Likely benign (Nov 04, 2023)
19-17762759-C-A			Uncertain significance (Aug 23, 2022)
19-17762764-C-A			Likely benign (Aug 12, 2023)
19-17762764-C-T			Likely benign (Oct 17, 2023)
19-17762767-G-T			Uncertain significance (Dec 31, 2023)
19-17762774-C-A			Uncertain significance (Sep 02, 2021)
19-17762785-G-T			Uncertain significance (Mar 07, 2021)
19-17762800-C-T			Likely benign (Aug 27, 2021)
19-17762814-C-T			Uncertain significance (Sep 08, 2023)
19-17762831-C-G			Uncertain significance (Sep 21, 2022)
19-17762832-T-C			Uncertain significance (Oct 05, 2022)
19-17762834-G-A			Uncertain significance (Oct 14, 2021)
19-17762834-G-C		Severe congenital neutropenia • Immunodeficiency 76	Pathogenic (Feb 10, 2021)
19-17762835-C-A			Uncertain significance (Feb 10, 2021)
19-17762835-C-T			Uncertain significance (Dec 27, 2023)
19-17762836-G-C			Likely benign (Oct 29, 2021)
19-17762847-G-C			Uncertain significance (Jun 27, 2022)
19-17762860-T-A			Likely benign (Jul 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FCHO1	protein_coding	protein_coding	ENST00000594202	26	40851

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00155	125732	0	15	125747	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.40	479	574	0.835	0.0000363	5694
Missense in Polyphen		136	176.64	0.76991		1834
Synonymous	0.0710	236	237	0.994	0.0000154	1867
Loss of Function	5.61	7	49.7	0.141	0.00000245	545

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. May regulate Bmp signaling by regulating clathrin-mediated endocytosis of Bmp receptors. {ECO:0000269|PubMed:20448150}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis (Consensus)

Recessive Scores

• pRec: 0.0981

Intolerance Scores

• loftool: 0.396
• rvis_EVS: -1.1
• rvis_percentile_EVS: 6.91

Haploinsufficiency Scores

• pHI: 0.543
• hipred: Y
• hipred_score: 0.566
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.811

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fcho1

Zebrafish Information Network

• Gene name: fcho1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: oblong

Gene ontology

• Biological process: clathrin coat assembly;membrane organization;clathrin-dependent endocytosis;plasma membrane tubulation
• Cellular component: nucleoplasm;cytoplasm;cytosol;cytoskeleton;plasma membrane;clathrin-coated pit;AP-2 adaptor complex;clathrin-coated vesicle
• Molecular function: protein binding;phospholipid binding;microtubule binding;cytoskeletal protein binding;tubulin binding;AP-2 adaptor complex binding