WASHC2C

Summary

WASHC2C (WASH complex subunit 2C, HGNC:23414) is a protein-coding gene on chromosome 10q11.22, encoding WASH complex subunit 2C (Q9Y4E1). Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport…. It is a selective cancer dependency (DepMap: 56.9% of cell lines).

Enables phosphatidylinositol phosphate binding activity; phosphatidylinositol-3,4-bisphosphate binding activity; and retromer complex binding activity. Involved in several processes, including endosomal transport; negative regulation of barbed-end actin filament capping; and protein localization to endosome. Located in cytosol; early endosome; and nucleolus. Part of WASH complex.

Source: NCBI Gene 253725 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 189 total
• Cancer dependency (DepMap): dependent in 56.9% of screened cell lines
• MANE Select transcript: NM_001330074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23414
Approved symbol	WASHC2C
Name	WASH complex subunit 2C
Location	10q11.22
Locus type	gene with protein product
Status	Approved
Aliases	VPEF, KIAA0592
Ensembl gene	ENSG00000172661
Ensembl biotype	protein_coding
OMIM	613631
Entrez	253725

Gene structure

Transcript identifiers

Ensembl transcripts: 91 — 88 protein_coding, 3 retained_intron

ENST00000359860, ENST00000374359, ENST00000374362, ENST00000420848, ENST00000471102, ENST00000485850, ENST00000537517, ENST00000540872, ENST00000623400, ENST00000884823, ENST00000884824, ENST00000884826, ENST00000884828, ENST00000884830, ENST00000884831, ENST00000884832, ENST00000884833, ENST00000884834, ENST00000884835, ENST00000884836, ENST00000884837, ENST00000884838, ENST00000884839, ENST00000884840, ENST00000884841, ENST00000884842, ENST00000884843, ENST00000884844, ENST00000884845, ENST00000884846, ENST00000884847, ENST00000884848, ENST00000884849, ENST00000884850, ENST00000884851, ENST00000884852, ENST00000884853, ENST00000884854, ENST00000884855, ENST00000919839, ENST00000919840, ENST00000919841, ENST00000919842, ENST00000919843, ENST00000919844, ENST00000919845, ENST00000919846, ENST00000919847, ENST00000919848, ENST00000919849, ENST00000919850, ENST00000968457, ENST00000968458, ENST00000968459, ENST00000968460, ENST00000968461, ENST00000968462, ENST00000968463, ENST00000968464, ENST00000968465, ENST00000968466, ENST00000968467, ENST00000968468, ENST00000968469, ENST00000968470, ENST00000968471, ENST00000968472, ENST00000968473, ENST00000968474, ENST00000968475, ENST00000968476, ENST00000968477, ENST00000968478, ENST00000968479, ENST00000968480, ENST00000968481, ENST00000968482, ENST00000968483, ENST00000968484, ENST00000968485, ENST00000968486, ENST00000968487, ENST00000968488, ENST00000968489, ENST00000968490, ENST00000968491, ENST00000968492, ENST00000968493, ENST00000968494, ENST00000968495, ENST00000968496

RefSeq mRNA: 28 — MANE Select: NM_001330074 NM_001169106, NM_001169107, NM_001330074, NM_001367393, NM_001367394, NM_001367395, NM_001367396, NM_001367397, NM_001367398, NM_001367399, NM_001367400, NM_001367401, NM_001367402, NM_001367403, NM_001367404, NM_001367405, NM_001367406, NM_001367407, NM_001367408, NM_001367409, NM_001367410, NM_001367411, NM_001367412, NM_001367413, NM_001367414, NM_001367415, NM_001367416, NM_015262

CCDS: CCDS44374, CCDS53528, CCDS53529, CCDS81453

Canonical transcript exons

ENST00000623400 — 31 exons

Exon	Start	End
ENSE00001659226	45754936	45755115
ENSE00002433882	45763388	45763489
ENSE00002437801	45787035	45787247
ENSE00002440475	45769449	45769618
ENSE00002440547	45785509	45785631
ENSE00002444220	45754486	45754545
ENSE00002449447	45759315	45759401
ENSE00002460400	45728862	45729026
ENSE00002464945	45744821	45744882
ENSE00002470242	45746600	45746647
ENSE00002477825	45777273	45777425
ENSE00002478867	45773256	45773358
ENSE00002484614	45750096	45750206
ENSE00002492050	45752588	45752706
ENSE00002500893	45737983	45738045
ENSE00002507871	45757012	45757139
ENSE00002511114	45750751	45750838
ENSE00002512724	45778953	45779135
ENSE00002523952	45765679	45765810
ENSE00002528275	45740073	45740246
ENSE00002530090	45753180	45753237
ENSE00003532725	45743390	45743483
ENSE00003536395	45727417	45727539
ENSE00003555651	45784821	45784901
ENSE00003589995	45790356	45790533
ENSE00003604576	45788871	45789491
ENSE00003656587	45784565	45784693
ENSE00003733535	45786612	45786674
ENSE00003756377	45792261	45792964
ENSE00003757746	45727266	45727320
ENSE00003787030	45751482	45751553

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5767 / max 297.4962, expressed in 1784 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104791	13.5767	1784

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.12	gold quality
monocyte	CL:0000576	94.67	gold quality
calcaneal tendon	UBERON:0003701	94.53	gold quality
leukocyte	CL:0000738	94.37	gold quality
transverse colon	UBERON:0001157	93.70	gold quality
rectum	UBERON:0001052	93.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.51	gold quality
endometrium	UBERON:0001295	93.32	gold quality
metanephros cortex	UBERON:0010533	93.23	gold quality
lymph node	UBERON:0000029	93.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.13	gold quality
granulocyte	CL:0000094	93.08	gold quality
cerebellar hemisphere	UBERON:0002245	93.02	gold quality
cerebellar cortex	UBERON:0002129	93.01	gold quality
spleen	UBERON:0002106	92.93	gold quality
cerebellum	UBERON:0002037	92.92	gold quality
right adrenal gland cortex	UBERON:0035827	92.64	gold quality
right ovary	UBERON:0002118	92.60	gold quality
small intestine	UBERON:0002108	92.53	gold quality
left ovary	UBERON:0002119	92.53	gold quality
endocervix	UBERON:0000458	92.49	gold quality
bone marrow	UBERON:0002371	92.48	gold quality
ovary	UBERON:0000992	92.46	gold quality
mucosa of transverse colon	UBERON:0004991	92.45	gold quality
colon	UBERON:0001155	92.43	gold quality
intestine	UBERON:0000160	92.40	gold quality
blood	UBERON:0000178	92.34	gold quality
right adrenal gland	UBERON:0001233	92.26	gold quality
right uterine tube	UBERON:0001302	92.19	gold quality
corpus callosum	UBERON:0002336	92.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.96
E-GEOD-110499	no	1213.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting WASHC2C, 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-4282	99.99	75.36	6408
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4318	99.38	66.94	1505

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 56.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• a cellular factor, VPEF, is exploited by vaccinia virus for cell entry through fluid phase endocytosis when vaccinia virus enters HeLa cells (PMID:18550675)
• WASH exists in a multiprotein complex containing FAM21, which links WASH to endosomes and is required for WASH-dependent retromer-mediated sorting. (PMID:19922874)
• Data show that a component of the WASH regulatory complex (SHRC), FAM21, directly interacts with the retromer CSC protein VPS35. (PMID:22513087)
• FAM21 not only functions as an integral component of the cytoplasmic WASH complex, but also modulates NF-kappaB gene transcription in the nucleus. (PMID:25431135)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	washc2c	ENSDARG00000062532
mus_musculus	Washc2	ENSMUSG00000024104
rattus_norvegicus	Washc2c	ENSRNOG00000011653
drosophila_melanogaster	FAM21	FBGN0034529

Paralogs (2): WASHC2A (ENSG00000099290), RCSD1 (ENSG00000198771)

Protein

Protein identifiers

WASH complex subunit 2C — Q9Y4E1 (reviewed: Q9Y4E1)

Alternative names: Vaccinia virus penetration factor

All UniProt accessions (3): Q9Y4E1, A0A0A0MT65, J3KP36

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC and retriever complexes subunits COMMD1 and CCDC93 as well as the retrievere complex subunit VPS35L. (Microbial infection) Plays a role in fluid-phase endocytosis, a process exploited by vaccinia intracellular mature virus (IMV) to enter cells. As a result, may facilitate the penetration of IMV into cells.

Subunit / interactions. Component of the WASH core complex also described as WASH regulatory complex (SHRC) composed of WASH (WASHC1, WASH2P or WASH3P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5; in the complex interacts (via N-terminus) directly with WASHC1. The WASH core complex associates via WASHC2 with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex. Interacts with VPS35; mediates the association with the retromer CSC complex. Interacts with FKBP15. Interacts with CCDC93, CCDC22, VPS35L; indicative for an association of the WASH core complex with the CCC and retriever complexes. May directly interact with TBC1D23.

Subcellular location. Early endosome membrane. Cell membrane.

Domain organisation. The LFa (leucine-phenylalanine-acidic) motif bind directly to VPS35 of retromer CSC; adjacent motifs can act cooperatively to bind multiple CSCs, although there is significant variability in the affinities of different motifs for retromer.

Miscellaneous. In human, WASHC2 has undergone evolutionary duplication, with 2 highly homologous family members WASHC2A and WASHC2C.

Similarity. Belongs to the FAM21 family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9Y4E1-7	1	yes
Q9Y4E1-4	2
Q9Y4E1-1	5
Q9Y4E1-2	3
Q9Y4E1-3	4
Q9Y4E1-5	6
Q9Y4E1-6	7

RefSeq proteins (28): NP_001162577, NP_001162578, NP_001317003, NP_001354322, NP_001354323, NP_001354324, NP_001354325, NP_001354326, NP_001354327, NP_001354328, NP_001354329, NP_001354330, NP_001354331, NP_001354332, NP_001354333, NP_001354334, NP_001354335, NP_001354336, NP_001354337, NP_001354338, NP_001354339, NP_001354340, NP_001354341, NP_001354342, NP_001354343, NP_001354344, NP_001354345, NP_056077 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029341	FAM21/CAPZIP	Domain

Pfam: PF15255

UniProt features (78 total): short sequence motif 21, compositionally biased region 19, region of interest 14, sequence conflict 9, splice variant 7, mutagenesis site 4, modified residue 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4E1-F1	48.34	0.04

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 (3): 539, 550, 909

Mutagenesis-validated functional residues (4):

Position	Phenotype
1031	disrupts interaction with f-actin-capping protein subunit alpha (capza1 or capza2 or capza3).
1299	impairs interaction with vps35.
1331	impairs interaction with vps35.
1333	disrupts interaction with vps35.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE

GO Biological Process (8): protein transport (GO:0015031), endosomal transport (GO:0016197), endocytic recycling (GO:0032456), regulation of Arp2/3 complex-mediated actin nucleation (GO:0034315), protein localization to endosome (GO:0036010), retrograde transport, endosome to Golgi (GO:0042147), regulation of substrate adhesion-dependent cell spreading (GO:1900024), negative regulation of barbed-end actin filament capping (GO:2000813)

GO Molecular Function (11): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), phosphatidylinositol-5-phosphate binding (GO:0010314), phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), phosphatidylinositol-4-phosphate binding (GO:0070273), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), phosphatidylinositol phosphate binding (GO:1901981), retromer complex binding (GO:1905394), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (8): nucleolus (GO:0005730), endosome (GO:0005768), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), early endosome membrane (GO:0031901), WASH complex (GO:0071203), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidylinositol phosphate binding	6
phosphatidylinositol bisphosphate binding	3
anion binding	3
endosomal transport	2
binding	2
cytoplasm	2
cellular anatomical structure	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
vesicle-mediated transport	1
intracellular transport	1
vesicle-mediated transport to the plasma membrane	1
Arp2/3 complex-mediated actin nucleation	1
regulation of actin nucleation	1
protein localization to organelle	1
intercellular transport	1
cytosolic transport	1
regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
positive regulation of actin filament depolymerization	1
positive regulation of actin filament polymerization	1
barbed-end actin filament capping	1
negative regulation of cellular component organization	1
regulation of barbed-end actin filament capping	1
phospholipid binding	1
protein-containing complex binding	1
nuclear lumen	1
intracellular membraneless organelle	1
endomembrane system	1
cytoplasmic vesicle	1
endosome	1
membrane	1
cell periphery	1
early endosome	1
endosome membrane	1
protein-containing complex	1

Protein interactions and networks

STRING

374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WASHC2C	WASHC4	Q2M389	969
WASHC2C	WASHC5	Q12768	961
WASHC2C	WASHC1	A8K0Z3	961
WASHC2C	WASHC3	Q9Y3C0	954
WASHC2C	IGF2R	P11717	770
WASHC2C	VPS35	Q96QK1	739
WASHC2C	CCDC93	Q567U6	723
WASHC2C	SNX27	Q96L92	711
WASHC2C	FKBP15	Q5T1M5	705
WASHC2C	CCDC22	O60826	653
WASHC2C	VPS29	Q9UBQ0	616
WASHC2C	WAS	P42768	613
WASHC2C	RAB11A	P24410	605
WASHC2C	ZFAND4	Q86XD8	561
WASHC2C	SNX3	O60493	542

IntAct

49 interactions, top by confidence:

A	B	Type	Score
VPS29	VPS35	psi-mi:“MI:0915”(physical association)	0.970
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
VPS35	WASHC2C	psi-mi:“MI:0915”(physical association)	0.620
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
VPS35	ENTR1	psi-mi:“MI:0914”(association)	0.530
VPS35	ANKRD50	psi-mi:“MI:0914”(association)	0.530
CAPZA1	CNOT1	psi-mi:“MI:0914”(association)	0.530
	AP3D1	psi-mi:“MI:0914”(association)	0.460
Capza1		psi-mi:“MI:0915”(physical association)	0.400
HDAC4	WASHC2C	psi-mi:“MI:0915”(physical association)	0.400
Vps35	WASHC2C	psi-mi:“MI:0915”(physical association)	0.370
FKBP15	WASHC2C	psi-mi:“MI:0915”(physical association)	0.370
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.350
VPS35	WASHC1	psi-mi:“MI:0914”(association)	0.350
VPS35	ILVBL	psi-mi:“MI:0914”(association)	0.350
VPS35	DNAJC13	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
PIN4	SEC22B	psi-mi:“MI:0914”(association)	0.350
VPS35	KIF2A	psi-mi:“MI:0914”(association)	0.350
HORMAD2	WASH3P	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): FAM21C (Affinity Capture-MS), FAM21C (Proximity Label-MS), FAM21C (Affinity Capture-MS), FAM21C (Affinity Capture-MS), FAM21C (Affinity Capture-MS), FAM21C (Affinity Capture-MS), FAM21C (Affinity Capture-Western), FAM21C (Affinity Capture-Western), FKBP15 (Affinity Capture-Western), VPS35 (Affinity Capture-Western), VPS26A (Affinity Capture-Western), VPS29 (Affinity Capture-Western), FAM21C (Proximity Label-MS), FAM21C (Affinity Capture-RNA), FAM21C (Proximity Label-MS)

ESM2 similar proteins: A0P8Z5, A4IGN8, B0KYV5, D3ZUI5, F1LR10, O00515, O46385, O54931, O75128, O75152, O75410, O95425, P42167, P57016, Q13625, Q1RMS0, Q3U1C4, Q3UMF0, Q53SF7, Q5NBX1, Q5PQN4, Q5PR69, Q5RC32, Q5RDC1, Q5REG6, Q5U301, Q5U5Q9, Q5ZJ26, Q5ZJJ1, Q5ZMW6, Q641Q2, Q6A098, Q6INC4, Q6NZF1, Q6Y685, Q7TNY7, Q80XI1, Q8CG79, Q8K3I4, Q8K4L3

Diamond homologs: Q3UZA1, Q3ZBT0, Q5RDC1, Q641Q2, Q6JBY9, Q6PGL7, Q80X08, Q91Y25, Q9Y4E1, Q552E2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WASHC2C	“form complex”	“WASH complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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
ER to Golgi Anterograde Transport	5	30.2×	2e-05
Golgi-to-ER retrograde transport	5	30.2×	2e-05
Intra-Golgi and retrograde Golgi-to-ER traffic	6	28.6×	5e-06
Transport to the Golgi and subsequent modification	5	23.4×	3e-05
Asparagine N-linked glycosylation	5	13.7×	3e-04
Membrane Trafficking	7	11.8×	3e-05
Vesicle-mediated transport	7	11.1×	3e-05
Adaptive Immune System	5	6.8×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
endocytic recycling	8	53.5×	4e-10
protein transport	7	7.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	153
Likely benign	18
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4963 predictions. Top by Δscore:

Variant	Effect	Δscore
10:45727538:GC:G	donor_gain	1.0000
10:45727599:G:GT	donor_gain	1.0000
10:45728860:A:AG	acceptor_gain	1.0000
10:45728861:G:GG	acceptor_gain	1.0000
10:45729022:AGAAT:A	donor_gain	1.0000
10:45729023:GAAT:G	donor_gain	1.0000
10:45729023:GAATG:G	donor_gain	1.0000
10:45729024:AATGT:A	donor_loss	1.0000
10:45729025:AT:A	donor_gain	1.0000
10:45729026:TGT:T	donor_loss	1.0000
10:45729027:G:C	donor_loss	1.0000
10:45729027:G:GG	donor_gain	1.0000
10:45729028:T:A	donor_loss	1.0000
10:45737981:A:AG	acceptor_gain	1.0000
10:45737982:G:GG	acceptor_gain	1.0000
10:45737982:GC:G	acceptor_gain	1.0000
10:45737982:GCGT:G	acceptor_gain	1.0000
10:45740067:TTGTA:T	acceptor_loss	1.0000
10:45740068:TGTA:T	acceptor_loss	1.0000
10:45740069:GTAG:G	acceptor_loss	1.0000
10:45740070:TA:T	acceptor_loss	1.0000
10:45740071:AGG:A	acceptor_loss	1.0000
10:45740202:G:GT	donor_gain	1.0000
10:45740242:CAAAG:C	donor_loss	1.0000
10:45740243:AAAG:A	donor_loss	1.0000
10:45740245:AGGT:A	donor_loss	1.0000
10:45740246:GGTGA:G	donor_loss	1.0000
10:45740247:GTGAA:G	donor_loss	1.0000
10:45740248:T:G	donor_loss	1.0000
10:45744820:GAA:G	acceptor_gain	1.0000

AlphaMissense

8905 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:45729015:T:C	F94L	1.000
10:45729017:C:A	F94L	1.000
10:45729017:C:G	F94L	1.000
10:45740124:G:C	A136P	1.000
10:45727516:T:A	W35R	0.999
10:45727516:T:C	W35R	0.999
10:45728863:T:C	L43P	0.999
10:45728875:T:C	L47P	0.999
10:45728938:T:C	L68P	0.999
10:45729001:T:C	L89P	0.999
10:45729016:T:C	F94S	0.999
10:45737984:G:C	R98P	0.999
10:45740104:T:C	L129P	0.999
10:45740136:G:C	G140R	0.999
10:45740137:G:A	G140D	0.999
10:45740157:G:C	A147P	0.999
10:45740170:T:C	L151P	0.999
10:45727518:G:C	W35C	0.998
10:45727518:G:T	W35C	0.998
10:45727534:G:C	A41P	0.998
10:45728866:T:C	L44P	0.998
10:45728883:T:C	F50L	0.998
10:45728885:C:A	F50L	0.998
10:45728885:C:G	F50L	0.998
10:45728971:T:C	L79P	0.998
10:45728995:T:C	L87P	0.998
10:45729023:G:C	E96D	0.998
10:45729023:G:T	E96D	0.998
10:45737983:C:A	R98S	0.998
10:45740116:T:A	V133D	0.998

dbSNP variants (sampled 300 via entrez): RS1002710851 (10:45727594 C>T), RS1002763261 (10:45727764 G>C), RS1003771820 (10:45726410 C>T), RS1005557567 (10:45728662 C>T), RS1006152615 (10:45727236 T>C,G), RS1006712099 (10:45728556 G>A), RS1007666074 (10:45727016 G>A,C), RS1008719401 (10:45725593 AC>A), RS1010120740 (10:45728052 A>G), RS1011054146 (10:45726503 T>A), RS1012927661 (10:45725633 C>A,T), RS1014651414 (10:45725243 C>A), RS1015641168 (10:45726966 A>C), RS1016502762 (10:45728668 G>A), RS1017972889 (10:45727868 G>A)

Disease associations

OMIM: gene MIM:613631 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000585_14	Mean corpuscular volume	3.000000e-11
GCST000587_14	Mean corpuscular hemoglobin	4.000000e-12
GCST007272_17	Pulse pressure	4.000000e-79
GCST90002398_173	Neutrophil count	4.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0005763	pulse pressure measurement
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Aflatoxin B1	increases methylation	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
FR900359	decreases phosphorylation	1
ethylbenzene	affects cotreatment, decreases expression, increases methylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants, Occupational	decreases expression, increases methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Estradiol	decreases expression	1
Gallic Acid	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Selenium	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Toluene	affects cotreatment, decreases expression, increases methylation	1
Vitamin E	affects cotreatment, decreases expression	1
Xylenes	affects cotreatment, decreases expression, increases methylation	1

Clinical trials (associated diseases)

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