FCHSD2

Summary

FCHSD2 (FCH and double SH3 domains 2, HGNC:29114) is a protein-coding gene on chromosome 11q13.4, encoding F-BAR and double SH3 domains protein 2 (O94868). Adapter protein that plays a role in endocytosis via clathrin-coated pits.

Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in clathrin-dependent endocytosis and positive regulation of Arp2/3 complex-mediated actin nucleation. Located in clathrin-coated pit and plasma membrane.

Source: NCBI Gene 9873 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 80 total
• MANE Select transcript: NM_014824

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29114
Approved symbol	FCHSD2
Name	FCH and double SH3 domains 2
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0769
Ensembl gene	ENSG00000137478
Ensembl biotype	protein_coding
OMIM	617556
Entrez	9873

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 22 protein_coding, 2 nonsense_mediated_decay

ENST00000311172, ENST00000409263, ENST00000409314, ENST00000409418, ENST00000409853, ENST00000422375, ENST00000432043, ENST00000458644, ENST00000543644, ENST00000891572, ENST00000891573, ENST00000891574, ENST00000891575, ENST00000891576, ENST00000891577, ENST00000891578, ENST00000891579, ENST00000891580, ENST00000891581, ENST00000891582, ENST00000891583, ENST00000960168, ENST00000960169, ENST00000960170

RefSeq mRNA: 1 — MANE Select: NM_014824 NM_014824

CCDS: CCDS8218

Canonical transcript exons

ENST00000409418 — 20 exons

Exon	Start	End
ENSE00000990257	72902543	72902638
ENSE00001062866	72841454	72841583
ENSE00001062872	72842621	72842841
ENSE00001119326	72887470	72887574
ENSE00001119329	72849755	72849889
ENSE00001119331	72867865	72868026
ENSE00001119334	72840877	72840959
ENSE00001119335	72889829	72889945
ENSE00001155156	72921828	72921950
ENSE00001155202	72836745	72838874
ENSE00001260311	72984088	72984216
ENSE00001260322	72985062	72985116
ENSE00001617612	73000990	73001134
ENSE00001933855	73141857	73142318
ENSE00003522086	72843151	72843328
ENSE00003538320	72843449	72843532
ENSE00003539091	73015809	73015885
ENSE00003594458	72988964	72989097
ENSE00003601589	73083695	73083740
ENSE00003633012	73140031	73140128

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 94.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3049 / max 753.7192, expressed in 1787 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121234	6.5262	1633
121232	6.3485	1352
121235	1.3857	795
121237	1.2592	718
121236	0.7522	415
121233	0.6527	351
121239	0.5221	262
121229	0.4347	186
121238	0.3820	181
121240	0.2923	127

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.16	gold quality
popliteal artery	UBERON:0002250	93.31	gold quality
tibial artery	UBERON:0007610	93.30	gold quality
aorta	UBERON:0000947	92.75	gold quality
blood vessel layer	UBERON:0004797	92.67	gold quality
lymph node	UBERON:0000029	92.63	gold quality
right coronary artery	UBERON:0001625	92.35	gold quality
descending thoracic aorta	UBERON:0002345	92.32	gold quality
thoracic aorta	UBERON:0001515	92.04	gold quality
ascending aorta	UBERON:0001496	91.99	gold quality
ventricular zone	UBERON:0003053	91.91	gold quality
left coronary artery	UBERON:0001626	91.86	gold quality
right lung	UBERON:0002167	91.86	gold quality
coronary artery	UBERON:0001621	91.63	gold quality
vermiform appendix	UBERON:0001154	91.31	gold quality
tibia	UBERON:0000979	91.24	gold quality
calcaneal tendon	UBERON:0003701	91.09	gold quality
ganglionic eminence	UBERON:0004023	90.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.49	gold quality
amygdala	UBERON:0001876	90.12	gold quality
superficial temporal artery	UBERON:0001614	90.06	gold quality
corpus callosum	UBERON:0002336	90.05	gold quality
gall bladder	UBERON:0002110	90.03	gold quality
sural nerve	UBERON:0015488	89.91	gold quality
monocyte	CL:0000576	89.66	gold quality
mononuclear cell	CL:0000842	89.63	gold quality
spleen	UBERON:0002106	89.54	gold quality
leukocyte	CL:0000738	89.52	gold quality
caecum	UBERON:0001153	89.22	gold quality
bone marrow cell	CL:0002092	89.21	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	25.44
E-CURD-122	yes	14.26
E-HCAD-35	yes	13.27
E-ANND-3	yes	12.08
E-MTAB-9067	yes	11.92
E-MTAB-6678	yes	6.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

186 targeting FCHSD2, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 7)

• our study, for the first time, demonstrates FCHSD2 as a predictor of outcome for Acute myeloid leukemia patients (PMID:22902056)
• A novel SNP-systemic lupus erythematosus association was identified between FCHSD2 and P2RY2, peaking at rs11235667 on a 33-kb haplotype upstream of ATG16L2. (PMID:26663301)
• Established 3 models of Carom-receptor complexes and their intracellular trafficking based on protein interaction and subcellular localization. Carom may mediate receptor endocytosis and transport endocytic receptors to the cytoplasm for receptor signaling and lysosome/proteasome degradation. Review. (PMID:28199211)
• Loss of FCHSD2 activity in nonsmall cell lung cancer (NSCLC) cells leads to increased cell-surface expression and altered signaling downstream of EGFR, resulting in enhanced cell proliferation and migration. (PMID:30249660)
• FCHSD2 controls oncogenic ERK1/2 signaling outcome by regulating endocytic trafficking. (PMID:32678845)
• FCHSD2 cooperates with CDC42 and N-WASP to regulate cell protrusion formation. (PMID:34520816)
• Endosomal actin branching, fission, and receptor recycling require FCHSD2 recruitment by MICAL-L1. (PMID:39382837)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	FCHSD2	ENSDARG00000091428
danio_rerio		ENSDARG00000110183
		ENSDARG00000113859
mus_musculus	Fchsd2	ENSMUSG00000030691
rattus_norvegicus	Fchsd2	ENSRNOG00000019319
drosophila_melanogaster	nwk	FBGN0263456
caenorhabditis_elegans	C26C6.8	WBGENE00007742

Paralogs (1): FCHSD1 (ENSG00000197948)

Protein

Protein identifiers

F-BAR and double SH3 domains protein 2 — O94868 (reviewed: O94868)

Alternative names: Carom, Protein nervous wreck 1, SH3 multiple domains protein 3

All UniProt accessions (7): O94868, B8ZZW8, C9JM66, E7ENZ2, E9PG19, H0Y6M2, H0YG35

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that plays a role in endocytosis via clathrin-coated pits. Contributes to the internalization of cell surface receptors, such as integrin ITGB1 and transferrin receptor. Promotes endocytosis of EGFR in cancer cells, and thereby contributes to the down-regulation of EGFR signaling. Recruited to clathrin-coated pits during a mid-to-late stage of assembly, where it is required for normal progress from U-shaped intermediate stage pits to terminal, omega-shaped pits. Binds to membranes enriched in phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate. When bound to membranes, promotes actin polymerization via its interaction with WAS and/or WASL which leads to the activation of the Arp2/3 complex. Does not promote actin polymerisation in the absence of membranes.

Subunit / interactions. Homodimer. Interacts (via SH3 domain 2) with ITSN1 (via SH3 domain 4). Recruited to clathrin-coated pits during a mid-to-late stage of assembly via interaction with ITSN1. Interacts (via SH3 domain 1) with WASL. Interacts with WAS. Interacts with CASK and MAGI1. CASK inhibits interaction with MAGI1.

Subcellular location. Cytoplasm. Cell junction. Membrane. Clathrin-coated pit. Cell membrane. Cell projection. Stereocilium.

Tissue specificity. Liver, brain, heart, placenta, skeletal muscle, pancreas, lung and kidney.

Post-translational modifications. Phosphorylated. Phosphorylation on a Ser residue is important for recruitment to the cell membrane and for its role in promoting endocytosis.

Domain organisation. The F-BAR domain has an atypical, flat shape and binds preferentially to flat membranes. Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions. Recruited to clathrin-coated pits via SH3 domain 2. The two SH3 domains cooperate to maintain the protein in an autoinhibited conformation that prevents promiscuous membrane binding.

Isoforms (3)

UniProt ID	Names	Canonical?
O94868-1	1	yes
O94868-2	2
O94868-3	3

RefSeq proteins (1): NP_055639* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001060	FCH_dom	Domain
IPR001452	SH3_domain	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR031160	F_BAR_dom	Domain
IPR034934	FCHSD2_F-BAR_dom	Domain
IPR035460	FCHSD_SH3_1	Domain
IPR035556	FCHSD2_SH3_2	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily

Pfam: PF00018, PF00611, PF14604

UniProt features (37 total): strand 11, mutagenesis site 9, domain 3, splice variant 3, region of interest 3, modified residue 2, compositionally biased region 2, chain 1, turn 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6GBU	X-RAY DIFFRACTION	3.44
2DL5	SOLUTION NMR
2DL7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94868-F1	75.76	0.44

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 (2): 675, 681

Mutagenesis-validated functional residues (9):

Position	Phenotype
478	loss of ability to promote actin polymerization; when associated with a-480.
480	loss of ability to promote actin polymerization; when associated with a-478.
521	loss of ability to promote actin polymerization; when associated with a-524.
524	loss of ability to promote actin polymerization; when associated with a-521.
576	abolishes interaction with itsn1 and location at clathrin-coated pits; when associated with s-607.
607	abolishes interaction with itsn1 and location at clathrin-coated pits; when associated with s-576.
622–623	abolishes interaction with itsn1.
681	impaired recruitment to the cell membrane.
681	increased recruitment to the cell membrane.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 351 (showing top): GCACCTT_MIR18A_MIR18B, FXR_IR1_Q6, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_ACTIN_NUCLEATION, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, TACAATC_MIR508, FOXO4_01, CAGGTCC_MIR492, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, USF_C, chr11q13, GOBP_CELL_CELL_SIGNALING

GO Biological Process (11): neuromuscular synaptic transmission (GO:0007274), protein transport (GO:0015031), regulation of actin filament polymerization (GO:0030833), positive regulation of actin filament polymerization (GO:0030838), membrane organization (GO:0061024), clathrin-dependent endocytosis (GO:0072583), positive regulation of Arp2/3 complex-mediated actin nucleation (GO:2000601), endocytosis (GO:0006897), positive regulation of cytoskeleton organization (GO:0051495), regulation of actin filament organization (GO:0110053), positive regulation of supramolecular fiber organization (GO:1902905)

GO Molecular Function (4): phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (10): plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), neuromuscular junction (GO:0031594), recycling endosome (GO:0055037), anchoring junction (GO:0070161), stereocilium shaft (GO:0120043), cytoplasm (GO:0005737), membrane (GO:0016020), stereocilium (GO:0032420), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
actin filament polymerization	2
regulation of supramolecular fiber organization	2
binding	2
membrane	2
chemical synaptic transmission	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
regulation of actin polymerization or depolymerization	1
regulation of protein polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
cellular component organization	1
receptor-mediated endocytosis	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
positive regulation of actin nucleation	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cytoskeleton organization	1
positive regulation of organelle organization	1
regulation of cytoskeleton organization	1
actin filament organization	1
regulation of actin cytoskeleton organization	1
positive regulation of cellular component organization	1
supramolecular fiber organization	1
anion binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
cell periphery	1
endomembrane system	1
synapse	1
endosome	1
cell junction	1
stereocilium	1

Protein interactions and networks

STRING

776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCHSD2	TRIM45	Q9H8W5	881
FCHSD2	STAC	Q99469	877
FCHSD2	SPART	Q8N0X7	840
FCHSD2	WASL	O00401	839
FCHSD2	SORBS1	Q9BX66	811
FCHSD2	SNX16	P57768	749
FCHSD2	KIR3DL1	P43629	720
FCHSD2	KIR3DL3	Q8N743	713
FCHSD2	WAS	P42768	704
FCHSD2	KIR2DL1	P43626	697
FCHSD2	KIR3DL2	P43630	661
FCHSD2	KIR2DL4	P78400	640
FCHSD2	CDK2	P24941	626
FCHSD2	ATG16L2	Q8NAA4	599
FCHSD2	KIR2DL3	P43628	598

IntAct

167 interactions, top by confidence:

A	B	Type	Score
MAGI1	FCHSD2	psi-mi:“MI:0915”(physical association)	0.720
FCHSD2	MAGI1	psi-mi:“MI:0915”(physical association)	0.720
FCHSD2	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FCHSD2	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
FAM9B	FCHSD2	psi-mi:“MI:0915”(physical association)	0.670
ABCF3	FCHSD2	psi-mi:“MI:0915”(physical association)	0.670
MTUS2	FCHSD2	psi-mi:“MI:0915”(physical association)	0.670
FCHSD2	ABCF3	psi-mi:“MI:0915”(physical association)	0.670
FCHSD2	FAM9B	psi-mi:“MI:0915”(physical association)	0.670
SNX9	WASL	psi-mi:“MI:0914”(association)	0.640
FCHSD2	GOPC	psi-mi:“MI:0407”(direct interaction)	0.590
	FCHSD2	psi-mi:“MI:0915”(physical association)	0.560
KIFC3	FCHSD2	psi-mi:“MI:0915”(physical association)	0.560
FCHSD2	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
FCHSD2	VCP	psi-mi:“MI:0915”(physical association)	0.510
FCHSD2	Cask	psi-mi:“MI:0914”(association)	0.500
FCHSD2	Cask	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (73): FCHSD2 (Two-hybrid), FCHSD2 (Two-hybrid), MTUS2 (Two-hybrid), ABCF3 (Two-hybrid), FAM9B (Two-hybrid), CCDC158 (Two-hybrid), CCDC85B (Two-hybrid), FCHSD2 (Two-hybrid), FCHSD2 (Reconstituted Complex), FCHSD2 (Affinity Capture-MS), FCHSD2 (Two-hybrid), FCHSD2 (Affinity Capture-MS), FCHSD2 (Two-hybrid), MAGI1 (Reconstituted Complex), MAGI1 (Affinity Capture-Western)

ESM2 similar proteins: A0A178VBJ0, A2XNL6, A7YY57, B9DFS6, E7FBF7, F4I0K9, F4IE65, F4IGZ2, O80875, O94868, P94017, Q08DK5, Q0JCC3, Q0WQX9, Q0WUQ1, Q10B79, Q1PE51, Q502I9, Q5PPJ9, Q6WWW4, Q7Y220, Q84JG2, Q84JR9, Q8GX47, Q8L5Z7, Q8LF20, Q8R3V5, Q8S9J8, Q8VY27, Q8VYT2, Q93YU8, Q940H8, Q9AQW1, Q9C865, Q9CA69, Q9FFX6, Q9FHH2, Q9FY95, Q9FYC8, Q9LML2

Diamond homologs: A1CEK6, A1DFN5, A2QW93, A4FU49, A4RF61, A7A261, A7E3N7, D3ZG83, F1LRS8, O42287, O55043, O60504, O94868, P10569, P19878, P29355, P32793, P38753, P39743, P43603, P49710, P52735, P62993, P62994, P80192, P87379, Q02779, Q06449, Q07883, Q08012, Q08DN7, Q0CJU8, Q0U6X7, Q14155, Q15811, Q16584, Q1E878, Q1KKW7, Q1KKZ1, Q2GT05

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	43.3×	5e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	41.2×	5e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	41.2×	5e-06
Assembly and cell surface presentation of NMDA receptors	10	38.5×	9e-12
Dopamine Neurotransmitter Release Cycle	5	37.6×	7e-06
Long-term potentiation	5	36.0×	8e-06
Neurexins and neuroligins	11	32.8×	6e-12
Protein-protein interactions at synapses	7	28.2×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	52.3×	4e-11
protein localization to synapse	6	46.0×	6e-07
receptor clustering	7	43.7×	5e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	29.7×	7e-06
protein-containing complex assembly	9	10.2×	2e-05
cell-cell adhesion	9	9.1×	5e-05
establishment of localization in cell	5	8.0×	8e-03
exocytosis	5	7.6×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4221 predictions. Top by Δscore:

Variant	Effect	Δscore
11:72840875:A:AC	donor_gain	1.0000
11:72840876:C:CC	donor_gain	1.0000
11:72840876:CAGGT:C	donor_gain	1.0000
11:72840960:C:CC	acceptor_gain	1.0000
11:72842838:CATA:C	acceptor_gain	1.0000
11:72842842:C:CC	acceptor_gain	1.0000
11:72843150:CCA:C	donor_gain	1.0000
11:72843192:T:TA	donor_gain	1.0000
11:72843324:CGAGC:C	acceptor_gain	1.0000
11:72843327:GCC:G	acceptor_loss	1.0000
11:72843328:CCT:C	acceptor_loss	1.0000
11:72843329:C:CC	acceptor_gain	1.0000
11:72843330:T:C	acceptor_loss	1.0000
11:72843333:G:GC	acceptor_gain	1.0000
11:72843342:A:C	acceptor_gain	1.0000
11:72843446:TA:T	donor_loss	1.0000
11:72843538:G:C	acceptor_gain	1.0000
11:72843545:A:C	acceptor_gain	1.0000
11:72843550:C:CT	acceptor_gain	1.0000
11:72843551:A:AC	acceptor_gain	1.0000
11:72843551:A:C	acceptor_gain	1.0000
11:72849751:AAAC:A	donor_loss	1.0000
11:72849752:AACC:A	donor_loss	1.0000
11:72849886:TAAG:T	acceptor_gain	1.0000
11:72867860:CGTA:C	donor_loss	1.0000
11:72867861:GTA:G	donor_loss	1.0000
11:72867862:TA:T	donor_loss	1.0000
11:72867863:A:AC	donor_gain	1.0000
11:72867864:C:CC	donor_gain	1.0000
11:72867864:C:CT	donor_loss	1.0000

AlphaMissense

4885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:72842688:G:T	P620Q	1.000
11:72842691:A:G	F619S	1.000
11:72842697:C:T	G617E	1.000
11:72842718:C:T	G610E	1.000
11:72842719:C:A	G610W	1.000
11:72842719:C:G	G610R	1.000
11:72842719:C:T	G610R	1.000
11:72842726:G:C	F607L	1.000
11:72842726:G:T	F607L	1.000
11:72842728:A:G	F607L	1.000
11:72842784:A:G	F588S	1.000
11:72842790:A:G	L586S	1.000
11:72843282:A:G	L525P	1.000
11:72843286:A:C	Y524D	1.000
11:72843294:G:C	P521R	1.000
11:72843294:G:T	P521Q	1.000
11:72843295:G:A	P521S	1.000
11:72843295:G:T	P521T	1.000
11:72843297:A:T	V520E	1.000
11:72843303:C:A	G518V	1.000
11:72843303:C:T	G518D	1.000
11:72843304:C:G	G518R	1.000
11:72843327:G:T	A510D	1.000
11:72843455:C:A	W507C	1.000
11:72843455:C:G	W507C	1.000
11:72843456:C:G	W507S	1.000
11:72843457:A:G	W507R	1.000
11:72843457:A:T	W507R	1.000
11:72843471:C:T	G502E	1.000
11:72843489:A:G	L496S	1.000

dbSNP variants (sampled 300 via entrez): RS1000016894 (11:72928986 C>T), RS1000031260 (11:73027820 C>T), RS1000037748 (11:72946192 T>C), RS1000074853 (11:72887130 T>G), RS1000076386 (11:73076564 A>G), RS1000079356 (11:72975436 T>C), RS1000089064 (11:73021424 G>C), RS1000091446 (11:72839645 G>A), RS1000100808 (11:72848957 A>G), RS1000123100 (11:72892607 T>G), RS1000143609 (11:72937075 G>A), RS1000148970 (11:72843657 A>C), RS1000150396 (11:73116734 C>T), RS1000151816 (11:72977138 G>A), RS1000153151 (11:73115258 T>C)

Disease associations

OMIM: gene MIM:617556 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001785_6	Crohn’s disease	4.000000e-07
GCST002094_8	Crohn’s disease	7.000000e-09
GCST003599_3	Systemic lupus erythematosus	7.000000e-11
GCST005987_48	Albumin-globulin ratio	6.000000e-17
GCST005989_23	Serum total protein levels	6.000000e-15
GCST006465_24	Endometrial cancer (endometrioid histology)	6.000000e-07
GCST008513_22	Health literacy	3.000000e-06
GCST010105_28	Nicotine dependence symptom count	5.000000e-06
GCST011956_127	Systemic lupus erythematosus	3.000000e-23

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005128	albumin:globulin ratio measurement
EFO:0010104	health literacy measurement
EFO:0009262	nicotine dependence symptom count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	5
trichostatin A	decreases expression, affects cotreatment	3
Acetaminophen	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	decreases expression, affects expression	3
Cisplatin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
versicolorin A	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression	1
Arsenic	affects methylation	1
Benzene	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression	1
Diazinon	increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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