FCHO1

Summary

FCHO1 (FCH and mu domain containing endocytic adaptor 1, HGNC:29002) is a protein-coding gene on chromosome 19p13.11, encoding F-BAR domain only protein 1 (O14526). Functions in an early step of clathrin-mediated endocytosis.

Enables AP-2 adaptor complex binding activity. Involved in several processes, including T cell receptor signaling pathway; clathrin coat assembly; and clathrin-dependent endocytosis. Located in cytosol; nucleoplasm; and plasma membrane. Is active in clathrin-coated pit. Implicated in primary immunodeficiency disease.

Source: NCBI Gene 23149 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 76 (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 899 total — 19 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_015122

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29002
Approved symbol	FCHO1
Name	FCH and mu domain containing endocytic adaptor 1
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0290
Ensembl gene	ENSG00000130475
Ensembl biotype	protein_coding
OMIM	613437
Entrez	23149

Gene structure

Transcript identifiers

Ensembl transcripts: 65 — 44 protein_coding, 10 retained_intron, 7 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000593385, ENST00000593833, ENST00000593870, ENST00000594068, ENST00000594202, ENST00000595023, ENST00000595033, ENST00000595549, ENST00000595594, ENST00000595749, ENST00000596309, ENST00000596462, ENST00000596507, ENST00000596522, ENST00000596536, ENST00000596865, ENST00000596951, ENST00000597076, ENST00000597474, ENST00000597512, ENST00000597718, ENST00000598067, ENST00000598086, ENST00000598539, ENST00000598960, ENST00000599236, ENST00000599766, ENST00000600058, ENST00000600201, ENST00000600209, ENST00000600393, ENST00000600676, ENST00000601247, ENST00000602111, ENST00000699176, ENST00000699177, ENST00000699196, ENST00000699197, ENST00000699198, ENST00000699199, ENST00000699200, ENST00000699201, ENST00000699202, ENST00000699203, ENST00000699204, ENST00000699205, ENST00000699206, ENST00000699207, ENST00000699208, ENST00000699209, ENST00000699210, ENST00000699211, ENST00000699212, ENST00000699213, ENST00000699214, ENST00000699215, ENST00000699216, ENST00000699217, ENST00000699218, ENST00000949279, ENST00000949280, ENST00000949281, ENST00000949282, ENST00000949283, ENST00000949284

RefSeq mRNA: 40 — MANE Select: NM_015122 NM_001161357, NM_001161358, NM_001161359, NM_001384370, NM_001384371, NM_001384372, NM_001384373, NM_001384374, NM_001384375, NM_001384376, NM_001384377, NM_001384378, NM_001384379, NM_001384380, NM_001384381, NM_001384384, NM_001384385, NM_001384386, NM_001384387, NM_001384388, NM_001384389, NM_001384390, NM_001384391, NM_001384392, NM_001384393, NM_001384394, NM_001384395, NM_001384396, NM_001384397, NM_001384398, NM_001384399, NM_001384400, NM_001384401, NM_001384402, NM_001384403, NM_001384404, NM_001384405, NM_001384406, NM_001384407, NM_015122

CCDS: CCDS32955, CCDS59365, CCDS59366, CCDS92558, CCDS92559, CCDS92560, CCDS92561

Canonical transcript exons

ENST00000596536 — 29 exons

Exon	Start	End
ENSE00000689692	17786574	17786629
ENSE00000871042	17784725	17784924
ENSE00000895226	17766669	17766810
ENSE00000895229	17770425	17770577
ENSE00000895247	17775056	17775080
ENSE00000895256	17776247	17776271
ENSE00000951693	17787682	17787846
ENSE00001504930	17775983	17776161
ENSE00001504932	17774394	17774478
ENSE00003028877	17788284	17788561
ENSE00003084528	17754592	17754681
ENSE00003099848	17754317	17754361
ENSE00003487332	17772457	17772555
ENSE00003495825	17776635	17776686
ENSE00003500327	17778609	17778884
ENSE00003510198	17762762	17762853
ENSE00003567265	17778137	17778228
ENSE00003582264	17783017	17783172
ENSE00003588187	17774239	17774283
ENSE00003589300	17781452	17781539
ENSE00003599437	17775456	17775513
ENSE00003607621	17781712	17781820
ENSE00003620258	17781231	17781343
ENSE00003639738	17755118	17755191
ENSE00003650542	17764375	17764449
ENSE00003651020	17772645	17772741
ENSE00003672270	17784103	17784235
ENSE00003791420	17770792	17770896
ENSE00003975978	17751477	17751577

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 93.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2957 / max 173.2776, expressed in 1385 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174543	5.4090	437
174542	3.5345	654
174548	2.9693	780
174546	0.5339	283
174541	0.4221	226
174547	0.2787	153
174545	0.0891	28
174544	0.0592	37

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.51	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.99	gold quality
oocyte	CL:0000023	89.78	gold quality
right frontal lobe	UBERON:0002810	89.74	gold quality
spinal cord	UBERON:0002240	89.58	gold quality
cortical plate	UBERON:0005343	88.46	gold quality
blood	UBERON:0000178	88.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.29	gold quality
lymph node	UBERON:0000029	88.10	gold quality
leukocyte	CL:0000738	87.98	gold quality
monocyte	CL:0000576	87.94	gold quality
cerebellar hemisphere	UBERON:0002245	87.75	gold quality
mononuclear cell	CL:0000842	87.74	gold quality
putamen	UBERON:0001874	87.60	gold quality
cerebellar cortex	UBERON:0002129	87.55	gold quality
prefrontal cortex	UBERON:0000451	87.21	gold quality
amygdala	UBERON:0001876	86.81	gold quality
corpus callosum	UBERON:0002336	86.80	gold quality
skin of leg	UBERON:0001511	86.78	gold quality
caudate nucleus	UBERON:0001873	86.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.25	gold quality
cerebellum	UBERON:0002037	85.46	gold quality
nucleus accumbens	UBERON:0001882	85.21	gold quality
frontal cortex	UBERON:0001870	84.98	gold quality
neocortex	UBERON:0001950	84.42	gold quality
hypothalamus	UBERON:0001898	84.19	gold quality
spleen	UBERON:0002106	84.17	gold quality
skin of abdomen	UBERON:0001416	83.88	gold quality
Ammon’s horn	UBERON:0001954	83.84	gold quality
cingulate cortex	UBERON:0003027	83.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting FCHO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-4732-5P	90.07	64.77	412

Literature-anchored findings (GeneRIF, showing 9)

• Involved in clathrin-coated vesicle formation. (PMID:17617719)
• study reports FCHo1/2 were required for plasma membrane clathrin-coated vesicle (CCV) budding & marked sites of CCV formation (PMID:20448150)
• show that the mu-homology domain of FCHO1/2 represents an endocytic interaction hub (PMID:22484487)
• The central linker of FCHO proteins acts as an allosteric regulator of the prime endocytic adaptor, AP-2. (PMID:25303365)
• Fcho1/2Eps15/RAP-2 ternary complexes to facilitate conformational activation of AP-2 by the Fcho1/2 interdomain linker to promote AP-2 cargo engagement. (PMID:27237791)
• A critical role of FCHO1 in the clathrin-mediated endocytosis and T cells development and function. (PMID:32098969)
• Liquid-like protein interactions catalyse assembly of endocytic vesicles. (PMID:33820972)
• Inflammatory Bowel Disease and Guillain Barre Syndrome in FCHO1 Deficiency. (PMID:33950325)
• FCH domain only 1 (FCHo1), a potential new biomarker for lung cancer. (PMID:34413495)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fcho1	ENSDARG00000015356
mus_musculus	Fcho1	ENSMUSG00000070000
rattus_norvegicus	Fcho1	ENSRNOG00000033912
drosophila_melanogaster	CG8176	FBGN0037702
caenorhabditis_elegans		WBGENE00018974

Paralogs (5): GAS7 (ENSG00000007237), SGIP1 (ENSG00000118473), PSTPIP1 (ENSG00000140368), PSTPIP2 (ENSG00000152229), FCHO2 (ENSG00000157107)

Protein

Protein identifiers

F-BAR domain only protein 1 — O14526 (reviewed: O14526)

All UniProt accessions (27): O14526, A0A0C3SFZ9, A0A8V8TMV7, A0A8V8TMX9, A0A8V8TNC3, A0A8V8TND1, A0A8V8TP91, A0A8V8TP96, A0A8V8TPA0, A0A8V8TPM7, A0A8V8TPN1, M0QXD1, M0QXW2, M0QXY1, M0QY09, M0QYA9, M0QYN8, M0QYT8, M0QZE1, M0QZF0, M0QZI9, M0QZS1, M0R0U5, M0R1K4, M0R2J7, M0R3E5, M0R3E7

UniProt curated annotations — full annotation on UniProt →

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. Involved in the regulation of T-cell poliferation and activation. Affects TCR clustering upon receptor triggering and modulates its internalisation, playing a role in TCR-dependent T-cell activation.

Subunit / interactions. May oligomerize and form homotetramer. Interacts with AP2A2 and AP2B1; 2 subunits of the adaptor protein complex AP-2. Interacts with DAB2. Interacts with clathrin (CLTC or CLTCL1). Interacts with EPS15, EPS15R and ITSN1. Interacts with AGFG1 and CALM. May interact with ACVR1; linking this receptor to clathrin-mediated endocytosis.

Subcellular location. Membrane. Clathrin-coated pit.

Tissue specificity. Predominantly expressed in lymphoid cells.

Disease relevance. Immunodeficiency 76 (IMD76) [MIM:619164] An autosomal recessive immunologic disorder characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Affected individuals have T-cell lymphopenia and variable B-cell or immunoglobulin abnormalities. Some patients develop B-cell lymphoma, others manifest neurologic features. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the FCHO family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14526-1	1	yes
O14526-2	2
O14526-3	3

RefSeq proteins (40): NP_001154829, NP_001154830, NP_001154831, NP_001371299, NP_001371300, NP_001371301, NP_001371302, NP_001371303, NP_001371304, NP_001371305, NP_001371306, NP_001371307, NP_001371308, NP_001371309, NP_001371310, NP_001371313, NP_001371314, NP_001371315, NP_001371316, NP_001371317, NP_001371318, NP_001371319, NP_001371320, NP_001371321, NP_001371322, NP_001371323, NP_001371324, NP_001371325, NP_001371326, NP_001371327, NP_001371328, NP_001371329, NP_001371330, NP_001371331, NP_001371332, NP_001371333, NP_001371334, NP_001371335, NP_001371336, NP_055937* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001060	FCH_dom	Domain
IPR018808	Muniscin_C	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR028565	MHD	Domain
IPR031160	F_BAR_dom	Domain
IPR042735	FCHO1_F-BAR	Domain
IPR054713	GMIP/FCHO2-like_FCH	Domain

Pfam: PF10291, PF22699

UniProt features (24 total): region of interest 6, modified residue 5, compositionally biased region 3, sequence variant 3, domain 2, splice variant 2, chain 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7OHI	X-RAY DIFFRACTION	1.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14526-F1	72.24	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 295, 347, 372, 530, 616

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 227 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_CLATHRIN_COAT_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOCC_COATED_VESICLE, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION, LEE_METASTASIS_AND_ALTERNATIVE_SPLICING_DN, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY, DASU_IL6_SIGNALING_UP, GOBP_LEUKOCYTE_CELL_CELL_ADHESION

GO Biological Process (5): clathrin coat assembly (GO:0048268), T cell receptor signaling pathway (GO:0050852), positive regulation of T cell activation (GO:0050870), clathrin-dependent endocytosis (GO:0072583), endocytosis (GO:0006897)

GO Molecular Function (2): AP-2 adaptor complex binding (GO:0035612), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), postsynaptic endocytic zone (GO:0098843), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Clathrin-mediated endocytosis	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
membrane	2
protein-containing complex assembly	1
antigen receptor-mediated signaling pathway	1
T cell activation	1
regulation of T cell activation	1
positive regulation of lymphocyte activation	1
positive regulation of leukocyte cell-cell adhesion	1
receptor-mediated endocytosis	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
protein-containing complex binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell periphery	1
endomembrane system	1
clathrin coat	1
postsynapse	1

Protein interactions and networks

STRING

1216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCHO1	EPS15	P42566	998
FCHO1	ITSN1	Q15811	998
FCHO1	ITSN2	Q9NZM3	996
FCHO1	TRIP10	Q15642	928
FCHO1	EPS15L1	Q9UBC2	926
FCHO1	EPN2	O95208	873
FCHO1	EPN3	Q9H201	818
FCHO1	NECAP1	Q8NC96	779
FCHO1	SNAP91	O60641	753
FCHO1	HIP1R	O75146	734
FCHO1	AMPH	P49418	655
FCHO1	FNBP1	Q96RU3	643
FCHO1	DAB2	P98082	618
FCHO1	EPN1	Q9Y6I3	613
FCHO1	FCHSD1	Q86WN1	608

IntAct

28 interactions, top by confidence:

A	B	Type	Score
FCHO1	PTK6	psi-mi:“MI:0915”(physical association)	0.670
LGALS14	FCHO1	psi-mi:“MI:0915”(physical association)	0.670
FCHO1	EXOSC5	psi-mi:“MI:0915”(physical association)	0.670
FCHO1	LGALS14	psi-mi:“MI:0915”(physical association)	0.670
PTK6	FCHO1	psi-mi:“MI:0915”(physical association)	0.670
EXOSC5	FCHO1	psi-mi:“MI:0915”(physical association)	0.670
FCHO1	Eps15	psi-mi:“MI:0915”(physical association)	0.520
Eps15	FCHO1	psi-mi:“MI:0915”(physical association)	0.520
CFTR	FCHO1	psi-mi:“MI:0915”(physical association)	0.370
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
PIWIL4	FCHO1	psi-mi:“MI:0914”(association)	0.350
FCHO1	EPS15	psi-mi:“MI:0914”(association)	0.350
FCHO1	POTEF	psi-mi:“MI:0914”(association)	0.350
YAF2	A2ML1	psi-mi:“MI:0914”(association)	0.350
P3H1	FCHO1	psi-mi:“MI:0914”(association)	0.350
C1QTNF2	FCHO1	psi-mi:“MI:0914”(association)	0.350
AP2S1	FCHO1	psi-mi:“MI:0914”(association)	0.350
DNAJC5	FCHO1	psi-mi:“MI:2364”(proximity)	0.270
Fcho2	FCHO1	psi-mi:“MI:0403”(colocalization)	0.270
FCHO1	nifJ	psi-mi:“MI:0915”(physical association)	0.000
FCHO1	ZBTB16	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (86): FCHO1 (Two-hybrid), LGALS14 (Two-hybrid), EXOSC5 (Two-hybrid), FCHO1 (Co-fractionation), FCHO1 (Biochemical Activity), FCHO1 (Reconstituted Complex), FCHO2 (Affinity Capture-MS), PCGF1 (Affinity Capture-MS), EPS15 (Affinity Capture-MS), EPS15L1 (Affinity Capture-MS), AP2A1 (Affinity Capture-MS), AP2A2 (Affinity Capture-MS), SRR (Affinity Capture-MS), AP1B1 (Affinity Capture-MS), EPS15 (Reconstituted Complex)

ESM2 similar proteins: A0PJT0, A1YB07, A2A6T1, A4IH82, B1A193, D3ZD05, O14526, O60239, O75145, O75335, O94876, P60469, P84903, Q0V8K7, Q13136, Q1LU99, Q1LZH7, Q2QL82, Q2QLG9, Q3TBD2, Q495M9, Q58CP9, Q5R9X9, Q5RB40, Q5U4W1, Q5U584, Q63ZY3, Q69ZZ6, Q6AYB8, Q6DIS8, Q6NZT2, Q6P402, Q7L8J4, Q80T11, Q86YS3, Q8BIJ7, Q8BQP8, Q8BX02, Q8CJ96, Q91Y80

Diamond homologs: D3ZYR1, E7FBF7, O14526, P0DJJ3, Q0JRZ9, Q3UQN2, Q502I9, Q5R807, Q5RDL3, Q6IZA3, Q8K285, Q8VD37, Q9BQI5, O55148, O60861

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FCHO1	“up-regulates quantity by stabilization”	“AP-2/clathrin vescicle”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

899 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	3
Uncertain significance	360
Likely benign	434
Benign	51

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1447115	NM_015122.3(FCHO1):c.1383del (p.Ser462fs)	Pathogenic
1457410	NM_015122.3(FCHO1):c.1834_1835dup (p.Arg613fs)	Pathogenic
2704841	NM_015122.3(FCHO1):c.2035_2038del (p.Arg679fs)	Pathogenic
2798462	NM_015122.3(FCHO1):c.1120G>T (p.Glu374Ter)	Pathogenic
2815349	NM_015122.3(FCHO1):c.2427G>A (p.Trp809Ter)	Pathogenic
2870389	NM_015122.3(FCHO1):c.1325C>G (p.Ser442Ter)	Pathogenic
3674429	NM_015122.3(FCHO1):c.756del (p.Phe252fs)	Pathogenic
3721416	NM_015122.3(FCHO1):c.2365C>T (p.Gln789Ter)	Pathogenic
4718541	NM_015122.3(FCHO1):c.276del (p.Leu92fs)	Pathogenic
4768425	NM_015122.3(FCHO1):c.1224dup (p.Pro409fs)	Pathogenic
4805852	NM_015122.3(FCHO1):c.163_188del (p.Ser55fs)	Pathogenic
805883	NM_015122.3(FCHO1):c.2036G>C (p.Arg679Pro)	Pathogenic
805884	NM_015122.3(FCHO1):c.100G>C (p.Ala34Pro)	Pathogenic
805885	NM_015122.3(FCHO1):c.2023dup (p.Val675fs)	Pathogenic
805886	NM_015122.3(FCHO1):c.489+1G>A	Pathogenic
805887	NM_015122.3(FCHO1):c.195-2A>C	Pathogenic
805888	NM_015122.3(FCHO1):c.1948C>T (p.Arg650Ter)	Pathogenic
996542	NM_015122.3(FCHO1):c.120-1G>C	Pathogenic
996543	NM_015122.3(FCHO1):c.27+1G>A	Pathogenic
2122626	NM_015122.3(FCHO1):c.1207+1G>A	Likely pathogenic
2630089	NM_015122.3(FCHO1):c.751A>T (p.Lys251Ter)	Likely pathogenic
3022338	NM_015122.3(FCHO1):c.1004-1C>T	Likely pathogenic

SpliceAI

4219 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17747811:GGAG:G	donor_gain	1.0000
19:17747812:GAGG:G	donor_gain	1.0000
19:17747813:AGGT:A	donor_loss	1.0000
19:17747814:GGTG:G	donor_loss	1.0000
19:17764369:CCCCA:C	acceptor_loss	1.0000
19:17764370:CCCA:C	acceptor_loss	1.0000
19:17764371:CCA:C	acceptor_loss	1.0000
19:17764373:A:AG	acceptor_gain	1.0000
19:17764373:AG:A	acceptor_gain	1.0000
19:17764374:G:GG	acceptor_gain	1.0000
19:17764374:GG:G	acceptor_gain	1.0000
19:17764446:TGGG:T	donor_gain	1.0000
19:17764447:GGG:G	donor_gain	1.0000
19:17764447:GGGG:G	donor_gain	1.0000
19:17764448:GG:G	donor_gain	1.0000
19:17764448:GGG:G	donor_gain	1.0000
19:17764448:GGGT:G	donor_loss	1.0000
19:17764449:GG:G	donor_gain	1.0000
19:17764450:G:GA	donor_loss	1.0000
19:17764450:G:GG	donor_gain	1.0000
19:17764451:T:A	donor_loss	1.0000
19:17764452:GA:G	donor_loss	1.0000
19:17766807:GAAG:G	donor_gain	1.0000
19:17766809:AGGT:A	donor_loss	1.0000
19:17766811:G:C	donor_loss	1.0000
19:17770423:A:AG	acceptor_gain	1.0000
19:17770424:G:GG	acceptor_gain	1.0000
19:17770424:GT:G	acceptor_gain	1.0000
19:17770549:A:T	donor_gain	1.0000
19:17770573:ACAAG:A	donor_loss	1.0000

AlphaMissense

5736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17766737:T:C	L88P	0.999
19:17766716:T:C	L81P	0.998
19:17766718:G:C	A82P	0.998
19:17762832:T:C	L33P	0.997
19:17762847:G:C	R38P	0.997
19:17766685:T:A	W71R	0.997
19:17766685:T:C	W71R	0.997
19:17766698:G:C	R75P	0.997
19:17766758:T:C	L95P	0.997
19:17772485:T:C	L208P	0.997
19:17781729:A:C	S616R	0.997
19:17781731:C:A	S616R	0.997
19:17781731:C:G	S616R	0.997
19:17783036:G:T	G653W	0.997
19:17783043:T:C	L655P	0.997
19:17786599:T:A	W818R	0.997
19:17786599:T:C	W818R	0.997
19:17787705:T:A	W836R	0.997
19:17787705:T:C	W836R	0.997
19:17787754:T:C	F852S	0.997
19:17764376:G:C	A41P	0.996
19:17764416:T:C	L54P	0.996
19:17766714:G:C	K80N	0.996
19:17766714:G:T	K80N	0.996
19:17766727:C:G	H85D	0.996
19:17772551:G:A	G230E	0.996
19:17776061:T:C	I361T	0.996
19:17781769:C:A	A629D	0.996
19:17784230:T:G	Y741D	0.996
19:17766712:A:G	K80E	0.995

dbSNP variants (sampled 300 via entrez): RS1000051042 (19:17768992 A>T), RS1000140049 (19:17779262 A>G), RS1000296448 (19:17785647 T>C), RS1000321446 (19:17755928 A>G), RS1000396148 (19:17750461 G>A), RS1000460531 (19:17780600 G>A), RS1000510035 (19:17751754 C>T), RS1000513296 (19:17779012 C>A,G,T), RS1000539960 (19:17754498 C>T), RS1000551058 (19:17769359 G>A), RS1000631840 (19:17784556 C>A,G,T), RS1000730318 (19:17749261 C>T), RS1000763385 (19:17749093 G>A), RS1000863630 (19:17766912 C>G,T), RS1000870926 (19:17763558 T>C)

Disease associations

OMIM: gene MIM:613437 | disease phenotypes: MIM:619164, MIM:202700

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 76	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency 76	Definitive	AR

Mondo (2): immunodeficiency 76 (MONDO:0030898), severe congenital neutropenia (MONDO:0018542)

Orphanet (2): Combined immunodeficiency due to FCHO1 deficiency (Orphanet:647804), Severe congenital neutropenia (Orphanet:42738)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001510	Growth delay
HP:0001744	Splenomegaly
HP:0001888	Decreased total lymphocyte count
HP:0002028	Chronic diarrhea
HP:0002583	Colitis
HP:0002716	Lymphadenopathy
HP:0003593	Infantile onset
HP:0003819	Death in childhood
HP:0005403	Decreased total T cell count
HP:0006532	Recurrent pneumonia
HP:0010976	Decreased total B cell count
HP:0011463	Childhood onset
HP:0012191	B-cell lymphoma
HP:0100501	Recurrent bronchiolitis

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005196_236	Coronary artery disease	8.000000e-14
GCST011364_29	Myocardial infarction	2.000000e-08
GCST011365_58	Myocardial infarction	4.000000e-12
GCST90002379_195	Basophil count	3.000000e-12
GCST90002394_448	Monocyte percentage of white cells	2.000000e-09
GCST90013407_100	Liver enzyme levels (gamma-glutamyl transferase)	3.000000e-43

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0007989	monocyte percentage of leukocytes
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
benzo(e)pyrene	increases methylation	1
abrine	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Methapyrilene	increases methylation	1
Niclosamide	increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	affects methylation	1
Asbestos, Serpentine	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SN32	HAP1 FCHO1 (-) 1	Cancer cell line	Male
CVCL_SN33	HAP1 FCHO1 (-) 2	Cancer cell line	Male
CVCL_SN34	HAP1 FCHO1 (-) 3	Cancer cell line	Male
CVCL_SN35	HAP1 FCHO1 (-) 4	Cancer cell line	Male
CVCL_SN36	HAP1 FCHO1 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

15 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01859637	PHASE4	TERMINATED	Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia
NCT00301834	PHASE2	COMPLETED	Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00909584	PHASE2	TERMINATED	Study of Ezatiostat (Telintra Tablets) for Treatment of Severe Chronic Neutropenia
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT04844177	PHASE2	UNKNOWN	Total Lymphoid Irradiation Pre-HSCT in Severe Congenital Neutropenia
NCT00295971	PHASE1	COMPLETED	Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00176852	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Hemoglobinopathy
NCT00305708	PHASE1/PHASE2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT02179359	Not specified	TERMINATED	Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening