VPS26A

Summary

VPS26A (VPS26 retromer complex component A, HGNC:12711) is a protein-coding gene on chromosome 10q22.1, encoding Vacuolar protein sorting-associated protein 26A (O75436). Acts as a component of the retromer cargo-selective complex (CSC).

This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 9559 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 43 total
• Druggable target: yes
• MANE Select transcript: NM_004896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12711
Approved symbol	VPS26A
Name	VPS26 retromer complex component A
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	Hbeta58, PEP8A
Ensembl gene	ENSG00000122958
Ensembl biotype	protein_coding
OMIM	605506
Entrez	9559

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000263559, ENST00000373382, ENST00000395098, ENST00000467852, ENST00000489656, ENST00000489794, ENST00000490696, ENST00000497022, ENST00000497564, ENST00000858432, ENST00000858433, ENST00000858434, ENST00000858435, ENST00000940626, ENST00000940627, ENST00000940628, ENST00000940629, ENST00000949228

RefSeq mRNA: 5 — MANE Select: NM_004896 NM_001035260, NM_001318944, NM_001318945, NM_001318946, NM_004896

CCDS: CCDS41536, CCDS7286

Canonical transcript exons

ENST00000263559 — 9 exons

Exon	Start	End
ENSE00003483920	69171156	69174412
ENSE00003489679	69168489	69168631
ENSE00003541904	69155812	69155887
ENSE00003546494	69158047	69158211
ENSE00003570825	69166042	69166110
ENSE00003611490	69132898	69133047
ENSE00003645793	69157007	69157163
ENSE00003690460	69162406	69162512
ENSE00003842145	69124178	69124280

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.0115 / max 1130.1496, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105322	40.7351	1810
105321	0.2764	96

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parietal pleura	UBERON:0002400	98.62	gold quality
esophagus squamous epithelium	UBERON:0006920	98.58	gold quality
parotid gland	UBERON:0001831	98.55	gold quality
visceral pleura	UBERON:0002401	98.55	gold quality
pleura	UBERON:0000977	98.52	gold quality
germinal epithelium of ovary	UBERON:0001304	98.34	gold quality
upper leg skin	UBERON:0004262	98.28	gold quality
skin of hip	UBERON:0001554	98.15	gold quality
endothelial cell	CL:0000115	98.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.10	gold quality
oral cavity	UBERON:0000167	98.04	gold quality
cauda epididymis	UBERON:0004360	98.02	gold quality
squamous epithelium	UBERON:0006914	98.00	gold quality
palpebral conjunctiva	UBERON:0001812	97.97	gold quality
renal glomerulus	UBERON:0000074	97.94	gold quality
lower lobe of lung	UBERON:0008949	97.94	gold quality
gingiva	UBERON:0001828	97.91	gold quality
epithelium of esophagus	UBERON:0001976	97.88	gold quality
metanephric glomerulus	UBERON:0004736	97.88	gold quality
gingival epithelium	UBERON:0001949	97.84	gold quality
colonic mucosa	UBERON:0000317	97.80	gold quality
eye	UBERON:0000970	97.80	gold quality
corpus epididymis	UBERON:0004359	97.80	gold quality
caput epididymis	UBERON:0004358	97.75	gold quality
mammalian vulva	UBERON:0000997	97.51	gold quality
cerebellar vermis	UBERON:0004720	97.49	gold quality
nephron tubule	UBERON:0001231	97.46	gold quality
blood vessel layer	UBERON:0004797	97.45	gold quality
hair follicle	UBERON:0002073	97.44	gold quality
mammary duct	UBERON:0001765	97.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): VPS35

miRNA regulators (miRDB)

108 targeting VPS26A, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273

Literature-anchored findings (GeneRIF, showing 15)

• These observations indicate that the mammalian retromer complex assembles by sequential association of SNX1/2 and Vps26-Vps29-Vps35 subcomplexes on endosomal membranes and that SNX1 and SNX2 play interchangeable but essential roles. (PMID:17101778)
• Membrane recruitment of the cargo-selective retromer subcomplex VPS35/29/26 is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5. (PMID:19531583)
• Colocalization of Vps26 paralogues with different endosomally located Rab proteins shows prolonged association of Vps26B-retromer with maturing endosomes relative to Vps26A-retromer. (PMID:21920005)
• Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endocytic trafficking and retromer function (PMID:22284051)
• Mutations in VPS26A are not a frequent cause of Parkinson’s disease. (PMID:24417787)
• Mutations in the gene composing the retromer cargo recognition subunit are not a common cause of Parkinson’s disease. (PMID:24684791)
• VPS26A binding increases the affinity of the SNX27 PDZ domain for PDZ- binding motifs by an order of magnitude, revealing cooperativity in cargo selection. (PMID:25136126)
• provides molecular insights into the essential role of Vps26 and Vps35 in Rab7-mediated recruitment of the core retromer complex (PMID:25367362)
• Mutagenesis studies coupled with coimmunoprecipitations revealed that retromer-mediated trafficking requires the Env cytoplasmic tail that we show binds directly to retromer components Vps35 and Vps26. (PMID:25393110)
• This study demonstrated that Genetic variability of VPS26A in parkinsonism. (PMID:25475142)
• The retromer complex is a highly conserved membrane trafficking assembly composed of three proteins - Vps26, Vps29 and Vps35, which are impaired in neurodegenerative diseases. (Review) (PMID:26965691)
• We investigated the modification of air pollution and diabetes association by a genetic risk score covering 63 T2D genes. Five single variants near GRB14, UBE2E2, PTPRD, VPS26A and KCNQ1 showed nominally significant interactions with PM10 (P<0.05). Our results suggest that genetic risk for T2D may modify susceptibility to air pollution through alterations in insulin sensitivity. (PMID:27281273)
• X-ray crystallographic analysis of a 4-component complex comprising the VPS26 & VPS35 subunits of retromer, sorting nexin SNX3, & recycling signal from the divalent cation transporter DMT1-II; analysis identifies a binding site for canonical recycling signals at the interface between VPS26 & SNX3; shows cooperative interactions among the VPS subunits, SNX3 & cargo that couple signal-recognition to membrane recruitment. (PMID:27889239)
• Novel crosstalk between Vps26a and Nox4 signaling during neurogenesis. (PMID:30464227)
• The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma. (PMID:36834898)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps26a	ENSDARG00000056549
mus_musculus	Vps26a	ENSMUSG00000020078
rattus_norvegicus	Vps26a	ENSRNOG00000030683
caenorhabditis_elegans		WBGENE00006931

Paralogs (2): VPS26B (ENSG00000151502), VPS26C (ENSG00000157538)

Protein

Protein identifiers

Vacuolar protein sorting-associated protein 26A — O75436 (reviewed: O75436)

Alternative names: Vesicle protein sorting 26A

All UniProt accessions (3): O75436, S4R2Y3, S4R3Q6

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5. Required for retrograde transport of lysosomal enzyme receptor IGF2R. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for the endosomal localization of WASHC2A (indicative for the WASH complex). Required for the endosomal localization of TBC1D5. Mediates retromer cargo recognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP. Involved in retromer-independent lysosomal sorting of F2R. Involved in recycling of ADRB2. Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins.

Subunit / interactions. Component of the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35. The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform. The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex. Interacts with VPS29, VPS35, SNX1, SNX2, SNX5, SNX6, SNX3, SNX27, RAB7A, ECPAS, EHD1, WASHC5, SORL1.

Subcellular location. Cytoplasm. Endosome membrane. Early endosome.

Induction. Down-regulated in Alzheimer disease. No polymorphism or variant is however associated with Alzheimer disease for VPS26A.

Similarity. Belongs to the VPS26 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75436-1	1	yes
O75436-2	2

RefSeq proteins (5): NP_001030337, NP_001305873, NP_001305874, NP_001305875, NP_004887* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014752	Arrestin-like_C_sf	Homologous_superfamily
IPR028934	Vps26-related	Family

Pfam: PF03643

UniProt features (39 total): strand 22, helix 4, sequence conflict 4, turn 3, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2FAU	X-RAY DIFFRACTION	2.1
5F0J	X-RAY DIFFRACTION	2.7
5F0P	X-RAY DIFFRACTION	2.78
5F0M	X-RAY DIFFRACTION	3.1
5F0L	X-RAY DIFFRACTION	3.2
7BLO	ELECTRON MICROSCOPY	9.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75436-F1	87.92	0.74

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 (1): 315

Mutagenesis-validated functional residues (1):

Position	Phenotype
235–236	abolishes interaction with vps35 and endosomal subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3238698	WNT ligand biogenesis and trafficking

MSigDB gene sets: 213 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, CMYB_01, MORF_HDAC1, MORF_HDAC2, GOBP_VESICLE_MEDIATED_TRANSPORT, CACCAGC_MIR138, GOBP_MACROAUTOPHAGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, MORF_RAB6A, USF_01, NRF2_Q4, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_ENDOCYTIC_RECYCLING, GOBP_RETROGRADE_TRANSPORT_ENDOSOME_TO_GOLGI

GO Biological Process (5): intracellular protein transport (GO:0006886), regulation of macroautophagy (GO:0016241), endocytic recycling (GO:0032456), retrograde transport, endosome to Golgi (GO:0042147), protein transport (GO:0015031)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (11): lysosome (GO:0005764), endosome (GO:0005768), early endosome (GO:0005769), cytosol (GO:0005829), endosome membrane (GO:0010008), retromer complex (GO:0030904), retromer, cargo-selective complex (GO:0030906), vesicle (GO:0031982), tubular endosome (GO:0097422), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
endosome	3
intracellular protein localization	2
endosomal transport	2
endomembrane system	2
membrane protein complex	2
protein transport	1
intracellular transport	1
regulation of autophagy	1
macroautophagy	1
vesicle-mediated transport to the plasma membrane	1
intercellular transport	1
cytosolic transport	1
transport	1
establishment of protein localization	1
binding	1
lytic vacuole	1
cytoplasmic vesicle	1
cytoplasm	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
retromer complex	1
membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS26A	SNX1	Q13596	999
VPS26A	VPS35	Q96QK1	999
VPS26A	VPS29	Q9UBQ0	999
VPS26A	SNX2	P82862	994
VPS26A	SNX27	Q96L92	986
VPS26A	SNX5	Q9Y5X3	986
VPS26A	SNX3	O60493	982
VPS26A	SNX6	Q9UNH7	941
VPS26A	SORL1	Q92673	931
VPS26A	TBC1D5	Q92609	910
VPS26A	SERPINE2	P07093	843
VPS26A	SORT1	Q99523	766
VPS26A	SNX4	O95219	762
VPS26A	WASHC5	Q12768	753
VPS26A	ANXA7	P20073	752

IntAct

130 interactions, top by confidence:

A	B	Type	Score
VPS35	VPS26A	psi-mi:“MI:0915”(physical association)	0.980
VPS26A	VPS35	psi-mi:“MI:0915”(physical association)	0.980
VPS35	VPS26A	psi-mi:“MI:0914”(association)	0.980
VPS35	VPS26A	psi-mi:“MI:0407”(direct interaction)	0.980
VPS26A	VPS35	psi-mi:“MI:0914”(association)	0.980
VPS26A	VPS35	psi-mi:“MI:0403”(colocalization)	0.980
VPS26A	VPS29	psi-mi:“MI:0915”(physical association)	0.930
VPS29	VPS26A	psi-mi:“MI:0914”(association)	0.930
VPS29	VPS26A	psi-mi:“MI:0915”(physical association)	0.930
VPS26A	TBC1D5	psi-mi:“MI:0914”(association)	0.810
TBC1D5	VPS26A	psi-mi:“MI:0914”(association)	0.810
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
ZSCAN12	VPS26A	psi-mi:“MI:0915”(physical association)	0.560
VPS26A	MORF4L1	psi-mi:“MI:0915”(physical association)	0.560
NDUFV2	VPS26A	psi-mi:“MI:0915”(physical association)	0.560
VPS26A	VPS26B	psi-mi:“MI:0914”(association)	0.530

BioGRID (258): VPS29 (Affinity Capture-MS), VPS35 (Affinity Capture-MS), TBC1D5 (Affinity Capture-MS), VPS26B (Affinity Capture-MS), VPS26A (Affinity Capture-MS), VPS26A (Reconstituted Complex), VPS26A (Reconstituted Complex), VPS26A (Co-fractionation), VPS26A (Co-fractionation), VPS26A (Co-fractionation), VPS26A (Co-fractionation), VPS29 (Co-fractionation), VPS35 (Co-fractionation), VPS26A (Affinity Capture-MS), BCS1L (Affinity Capture-MS)

ESM2 similar proteins: A0A7J6K9S4, A5PF44, C4R360, C5DL84, C5DRZ0, O01258, O17972, O45782, O75436, P30647, P40335, P40336, P53179, Q02331, Q09219, Q0VD53, Q10243, Q17388, Q18268, Q19829, Q28HT6, Q4G0F5, Q55CA0, Q5BKM4, Q5R436, Q5RAV3, Q68F29, Q6AY86, Q6CTM7, Q6DFB9, Q6DFU4, Q6DH23, Q6DTM3, Q6FWV1, Q6IRD0, Q6PAW0, Q6PB19, Q6PBN2, Q6TNP8, Q754G2

Diamond homologs: O01258, O75436, P40335, P40336, Q0VD53, Q10243, Q28HT6, Q4G0F5, Q55CA0, Q5BKM4, Q5R436, Q68F29, Q6AY86, Q6DFB9, Q6DFU4, Q6DH23, Q6IRD0, Q6TNP8, Q7ZV03, Q8C0E2, Q8I4T1, Q9FJD0, Q9T091, Q9W552

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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.

GO biological processes:

GO term	Partners	Fold	FDR
retrograde transport, endosome to Golgi	9	23.4×	1e-07
endocytic recycling	5	16.9×	2e-03
protein transport	11	6.1×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1533 predictions. Top by Δscore:

Variant	Effect	Δscore
10:69123785:G:GT	donor_gain	1.0000
10:69132891:A:AG	acceptor_gain	1.0000
10:69132895:CAG:C	acceptor_gain	1.0000
10:69132896:A:AG	acceptor_gain	1.0000
10:69132896:AGA:A	acceptor_gain	1.0000
10:69132897:G:GA	acceptor_gain	1.0000
10:69132897:GA:G	acceptor_gain	1.0000
10:69132897:GAG:G	acceptor_gain	1.0000
10:69132897:GAGT:G	acceptor_gain	1.0000
10:69132897:GAGTT:G	acceptor_gain	1.0000
10:69133044:A:T	donor_gain	1.0000
10:69133044:AAAGG:A	donor_loss	1.0000
10:69133046:AGG:A	donor_loss	1.0000
10:69133049:T:G	donor_loss	1.0000
10:69156995:A:AG	acceptor_gain	1.0000
10:69156996:A:G	acceptor_gain	1.0000
10:69156997:A:AG	acceptor_gain	1.0000
10:69157005:A:AG	acceptor_gain	1.0000
10:69157005:AGAAC:A	acceptor_loss	1.0000
10:69157006:G:GA	acceptor_loss	1.0000
10:69157006:G:GG	acceptor_gain	1.0000
10:69157006:GA:G	acceptor_gain	1.0000
10:69157006:GAA:G	acceptor_gain	1.0000
10:69157050:A:AG	acceptor_gain	1.0000
10:69157051:G:GG	acceptor_gain	1.0000
10:69157159:TTGAG:T	donor_loss	1.0000
10:69157160:TGAG:T	donor_loss	1.0000
10:69157161:GAGGT:G	donor_loss	1.0000
10:69157162:AGGTA:A	donor_loss	1.0000
10:69157163:GGTA:G	donor_loss	1.0000

AlphaMissense

2170 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:69133037:T:A	V48D	1.000
10:69133043:G:A	G50E	1.000
10:69155878:G:C	G74R	1.000
10:69155879:G:A	G74D	1.000
10:69157039:T:C	F88L	1.000
10:69157041:T:A	F88L	1.000
10:69157041:T:G	F88L	1.000
10:69157109:T:C	F111S	1.000
10:69157154:T:A	V126D	1.000
10:69158112:T:A	V151D	1.000
10:69158157:T:A	M166K	1.000
10:69158157:T:C	M166T	1.000
10:69158157:T:G	M166R	1.000
10:69158158:G:A	M166I	1.000
10:69158158:G:C	M166I	1.000
10:69158158:G:T	M166I	1.000
10:69158159:G:A	E167K	1.000
10:69158162:G:A	V168M	1.000
10:69158162:G:C	V168L	1.000
10:69158162:G:T	V168L	1.000
10:69158163:T:A	V168E	1.000
10:69158163:T:C	V168A	1.000
10:69158165:G:A	G169S	1.000
10:69158165:G:C	G169R	1.000
10:69158165:G:T	G169C	1.000
10:69158166:G:A	G169D	1.000
10:69158166:G:T	G169V	1.000
10:69158169:T:A	I170N	1.000
10:69158169:T:G	I170S	1.000
10:69158181:T:A	L174Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000036974 (10:69135171 C>T), RS1000086328 (10:69166532 A>G), RS1000194877 (10:69137845 T>G), RS1000225815 (10:69137986 A>T), RS1000254431 (10:69129547 A>G), RS1000255813 (10:69122787 C>A,G), RS1000295947 (10:69170549 G>A), RS1000336874 (10:69142162 C>G,T), RS1000441816 (10:69151836 A>G,T), RS1000455328 (10:69162104 G>A), RS1000524046 (10:69136568 CT>C), RS1000604866 (10:69129205 A>C,G), RS1000723719 (10:69147970 C>T), RS1000758011 (10:69169721 G>A), RS1000930705 (10:69140529 G>A)

Disease associations

OMIM: gene MIM:605506 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001213_3	Type 2 diabetes	4.000000e-08
GCST001533_13	Immune reponse to smallpox (secreted IL-1beta)	1.000000e-09
GCST002110_3	Glycemic traits (pregnancy)	1.000000e-22
GCST007847_98	Type 2 diabetes	3.000000e-09
GCST010989_84	Body size at age 10	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004307	glucose tolerance test
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067011 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, affects response to substance	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects response to substance	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylparaben	increases expression	1
perfluorooctanoic acid	decreases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Benzene	increases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Endosulfan	decreases expression	1
Etoposide	affects expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Phthalic Acids	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652811	Binding	Binding affinity to human VPS26A incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TX51	HAP1 VPS26A (-) 1	Cancer cell line	Male
CVCL_TX52	HAP1 VPS26A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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