FCHO1

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

Basic information

Region (hg38): 19:17747718-17788568

Links

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

Phenotypes

GenCC

Source: genCC

• immunodeficiency 76 (Strong), mode of inheritance: AR
• immunodeficiency 76 (Definitive), 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 (703 variants)
• not_specified (124 variants)
• Immunodeficiency_76 (10 variants)
• FCHO1-related_disorder (6 variants)
• Severe_congenital_neutropenia (6 variants)
• Immunodeficiency_with_T_and_B_cell_lymphopenia (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. These statistics are base on transcript: NM_000015122.3. 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	189	7	201
missense	2		297	13	4	316
nonsense	5	1				6
start loss						0
frameshift	5		2			7
splice donor/acceptor (+/-2bp)	4	2	1			7
Total	16	3	305	202	11

Highest pathogenic variant AF is 0.0000043368195

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