STAB2

Summary

STAB2 (stabilin 2, HGNC:18629) is a protein-coding gene on chromosome 12q23.3, encoding Stabilin-2 (Q8WWQ8). Phosphatidylserine receptor that enhances the engulfment of apoptotic cells.

This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 15 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to bind and endocytose ligands such as hyaluronan, low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein has been shown to cycle between the plasma membrane and lysosomes.

Source: NCBI Gene 55576 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 368 total
• MANE Select transcript: NM_017564

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18629
Approved symbol	STAB2
Name	stabilin 2
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434E0321, FELL, STAB-2, HARE, FEEL-2, SCARH1
Ensembl gene	ENSG00000136011
Ensembl biotype	protein_coding
OMIM	608561
Entrez	55576

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 retained_intron, 2 protein_coding, 1 nonsense_mediated_decay

ENST00000388887, ENST00000548073, ENST00000548579, ENST00000549474, ENST00000549798, ENST00000552777

RefSeq mRNA: 1 — MANE Select: NM_017564 NM_017564

CCDS: CCDS31888

Canonical transcript exons

ENST00000388887 — 69 exons

Exon	Start	End
ENSE00000818262	103739412	103739468
ENSE00000922885	103730116	103730256
ENSE00000922887	103731576	103731635
ENSE00000922888	103733006	103733182
ENSE00000922889	103735491	103735580
ENSE00000922890	103737634	103737780
ENSE00000922893	103740630	103740756
ENSE00000922895	103742405	103742554
ENSE00000922901	103748963	103749156
ENSE00000922902	103750579	103750720
ENSE00000922905	103753220	103753353
ENSE00001194009	103746597	103746704
ENSE00001194013	103745173	103745277
ENSE00001504274	103728849	103728995
ENSE00001504275	103727267	103727350
ENSE00001504276	103726116	103726163
ENSE00001504277	103724975	103725094
ENSE00001504278	103717770	103717841
ENSE00001504279	103715815	103715888
ENSE00001504280	103713643	103713768
ENSE00001504282	103711471	103711516
ENSE00001504283	103708441	103708536
ENSE00001504284	103706792	103706987
ENSE00001513480	103755302	103755467
ENSE00002326957	103673907	103674087
ENSE00002327690	103699096	103699227
ENSE00002331762	103683205	103683300
ENSE00002331830	103660331	103660384
ENSE00002334513	103594395	103594510
ENSE00002335547	103668643	103668729
ENSE00002338579	103638016	103638212
ENSE00002339362	103650496	103650578
ENSE00002340459	103652556	103652705
ENSE00002342179	103670696	103670807
ENSE00002345824	103703148	103703276
ENSE00002348000	103655251	103655307
ENSE00002352228	103675928	103676021
ENSE00002356311	103669541	103669627
ENSE00002361546	103637111	103637236
ENSE00002361702	103758170	103758289
ENSE00002364068	103622042	103622111
ENSE00002364142	103704558	103704614
ENSE00002370133	103690424	103690538
ENSE00002371189	103660683	103660763
ENSE00002372376	103688168	103688215
ENSE00002375454	103662846	103662998
ENSE00002398248	103590897	103591030
ENSE00002400819	103640123	103640256
ENSE00002401132	103677453	103677611
ENSE00002405626	103648690	103648823
ENSE00002406046	103655456	103655581
ENSE00002406434	103631598	103631693
ENSE00002417766	103692812	103692889
ENSE00002418289	103695550	103695648
ENSE00002418575	103684989	103685084
ENSE00002418744	103763492	103763608
ENSE00002419065	103705632	103705727
ENSE00002419281	103761300	103761410
ENSE00002419566	103689846	103689982
ENSE00002420576	103620468	103620553
ENSE00002425590	103766286	103766719
ENSE00002426555	103762274	103762402
ENSE00002427725	103666291	103666353
ENSE00002427925	103654555	103654698
ENSE00002429568	103695737	103695844
ENSE00002698916	103587273	103587557
ENSE00003466760	103712367	103712443
ENSE00003548355	103755612	103755718
ENSE00003551590	103759133	103759273

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 97.07.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4010 / max 197.5255, expressed in 40 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127698	0.4010	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	97.07	gold quality
right lobe of liver	UBERON:0001114	84.00	gold quality
liver	UBERON:0002107	82.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.15	gold quality
sperm	CL:0000019	74.90	silver quality
male germ cell	CL:0000015	73.32	silver quality
lymph node	UBERON:0000029	72.74	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.36	gold quality
lower esophagus	UBERON:0013473	71.24	gold quality
oocyte	CL:0000023	69.86	gold quality
triceps brachii	UBERON:0001509	69.39	gold quality
gluteal muscle	UBERON:0002000	69.24	gold quality
superficial temporal artery	UBERON:0001614	68.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	68.44	gold quality
popliteal artery	UBERON:0002250	67.15	gold quality
tibial artery	UBERON:0007610	67.08	gold quality
secondary oocyte	CL:0000655	66.91	gold quality
body of uterus	UBERON:0009853	66.77	gold quality
aorta	UBERON:0000947	66.43	gold quality
ascending aorta	UBERON:0001496	65.94	gold quality
thoracic aorta	UBERON:0001515	65.65	gold quality
transverse colon	UBERON:0001157	65.60	gold quality
colon	UBERON:0001155	65.43	gold quality
gall bladder	UBERON:0002110	65.01	gold quality
large intestine	UBERON:0000059	64.98	gold quality
rectum	UBERON:0001052	64.75	gold quality
left testis	UBERON:0004533	64.72	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	64.31	gold quality
left coronary artery	UBERON:0001626	64.29	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	3364.54
E-HCAD-9	yes	15.93
E-CURD-112	yes	11.99
E-MTAB-9067	yes	8.49
E-ANND-3	yes	7.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, HOXC9

miRNA regulators (miRDB)

33 targeting STAB2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
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-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-135A-2-3P	98.40	66.74	442
HSA-MIR-135B-3P	98.40	67.35	426
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-6862-3P	97.92	64.86	531
HSA-MIR-4632-5P	97.82	65.38	1470

Literature-anchored findings (GeneRIF, showing 35)

• code for homologous transmembrane proteins featuring seven fasciclin-like adhesion domains, 18-20 epidermal-growth-factor domains, one X-link domain and three to six B-(X(7))-B hyaluronan-binding motifs (PMID:11829752)
• amino acid sequence of 190-kDa protein composed of 1416 amino acids and alignment with rat sequence (PMID:12626425)
• HARE has a role in endocytosis and species-specific glycosaminoglycan affinity (PMID:15208308)
• A majority of HARE isoform is intracellular, within the endocytic system, suggesting transient surface residency typical of an active endocytic recycling receptor. (PMID:17145755)
• study provides evidence that stabilin-2 is a novel phosphatidylserine receptor, which performs a key function in the rapid clearance of cell corpses (PMID:17962816)
• GULP is a likely downstream molecule in the stabilin-2-mediated signaling pathway and plays an important role in stabilin-2-mediated phagocytosis (PMID:18230608)
• when HARE binds HA, that leads to activation of ERK1/2, important mediators of intracellular signal transduction. (PMID:18387958)
• HARE in the sinusoidal endothelial cells of lymph nodes and liver likely mediates the efficient systemic clearance of Hep and many different Hep-binding protein complexes from the lymphatic and vascular c (PMID:18434317)
• HARE binds to hyaluronan and heparin simultaneously (PMID:18499864)
• Thymosin beta4 is a downstream molecule of stabilin-2 that plays a role in stabilin-2-mediated cell corpse clearance. (PMID:18519035)
• although NPLY may be the most important motif, it functions together with two other endocytic motifs; thus three signal sequences (YSYFRI, FQHF, and NPLY) provide redundancy to mediate coated pit targeting and endocytosis of HARE (PMID:18539600)
• Epidermal growth factor (EGF)-like domain repeats (EGFrp) in stabilin-2 can directly and specifically recognize phosphatidylserine. (PMID:18573870)
• Both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are cleared by HARE/Stab2. The differences in the affinities of HARE binding to LMWH and UFH likely explain the longer in vivo circulating half-life of LMWH compared with UFH. (PMID:19359419)
• The results indicate that Link domain N-glycans stabilize interactions that facilitate HA binding to HARE. (PMID:20466649)
• Ligament Flavum (LF) hypertrophy is accompanied by increased CD44 and CD44v5 expression. CD44v6 expression is not enhanced in LF hypertrophy. (PMID:22052472)
• knockdown of endogenous alphavbeta5 expression or treatment with a function-blocking alphavbeta5 antibody significantly decreased stabilin-2-mediated phagocytosis in the absence of soluble factors (PMID:22566688)
• stabilin-2 acts as a receptor for necrotic cell clearance. (PMID:23416077)
• Hyaluronan binding to HARE mediates NF-kappaB-activated gene expression in a dose-dependent manner. (PMID:23530033)
• Loss of Stabilin-2 expression in peri-tumourous transdifferentiated liver endothelial cells correlates with increased survival by preventing endothelial-tumour cell adhesive interactions and microvascular invasion. (PMID:23870052)
• HARE may be part of a systemic tissue-stress sensor feedback system that responds to abnormal tissue turnover or damage as a danger signal (PMID:24247245)
• a Link domain complex N-glycan is required specifically for HARE.hyaluronic acid-mediated activation of ERK1/2 and NF-kappaB-mediated gene expression (PMID:24942734)
• HARE/Stabilin-2 splice variants are expressed in bone marrow, lymph node, and spleen (PMID:25446080)
• Data show that the hyaluronan receptor for endocytosis (HARE) NPLY2519 motif is necessary for both extracellular signal-regulated kinases ERK1/2 and NF-kappa B (NF-kappaB)signaling and that Tyr2519 is critical for these functions. (PMID:27100626)
• Stabilin-2 can play a critical role in the first entrapping step of LN metastasis through homotypic interaction with the lymphatic endothelium and appears to be a tumor biomarker predicting for LN metastasis in patients with solid tumors (PMID:27919991)
• Structural Determinants for the Interactions of Chemically Modified Nucleic Acids with the Stabilin-2 Clearance Receptor. (PMID:29589907)
• stabilin-2-expressing cells bind and internalize VWF and FVIII in a VWF-dependent manner, and the stabilin-2 variant p.E2377K significantly decreased stabilin-2 expression and impaired VWF endocytosis in a heterologous expression system (PMID:30124466)
• Macrophages likely require full-length Stab2 for efficient binding and phagocytosis of bacteria or apoptotic cells, since cell-binding domains are throughout the receptor. (PMID:31500161)
• Whole-exome sequencing identifies rare variants in STAB2 associated with venous thromboembolic disease. (PMID:32457982)
• Genome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus. (PMID:33493351)
• High expression of Stabilin-2 predicts poor prognosis in non-small-cell lung cancer. (PMID:34227915)
• A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/beta-catenin signaling pathway. (PMID:34863303)
• Loss of SATB2 and CDX2 expression is associated with DNA mismatch repair protein deficiency and BRAF mutation in colorectal cancer. (PMID:37583001)
• Highly oxidized albumin is cleared by liver sinusoidal endothelial cells via the receptors stabilin-1 and -2. (PMID:37926735)
• Stabilin-2 mediated apoptotic cell phagocytosis induces interleukin-10 expression by p38 and Pbx1 signaling. (PMID:38480573)
• Oncogenic Role of SATB2 In Vitro: Regulator of Pluripotency, Self-Renewal, and Epithelial-Mesenchymal Transition in Prostate Cancer. (PMID:38891096)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	stab2	ENSDARG00000045748
mus_musculus	Stab2	ENSMUSG00000035459
rattus_norvegicus	Stab2	ENSRNOG00000038948

Paralogs (2): STAB1 (ENSG00000010327), TNFAIP6 (ENSG00000123610)

Protein

Protein identifiers

Stabilin-2 — Q8WWQ8 (reviewed: Q8WWQ8)

Alternative names: FAS1 EGF-like and X-link domain-containing adhesion molecule 2, Fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor 2, Hyaluronan receptor for endocytosis

All UniProt accessions (3): Q8WWQ8, H0YHA5, H0YIF3

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Also acts, in different species, as a primary systemic scavenger receptor for heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), nonglycosaminoglycan (GAG), acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides and advanced glycation end products (AGE). May serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidity of bodily liquids by resorption of hyaluronan. Counter receptor which plays an important role in lymphocyte recruitment in the hepatic vasculature. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. The proteolytically processed 190 kDa form also functions as an endocytosis receptor for heparin internalization as well as HA and CS.

Subunit / interactions. Interacts with GULP1 and heparin. Also interacts with alpha-M/beta-2 integrin (ITGAM and ITGB2) and thymosin beta 4 (TMSB4X and/or TMSB4Y).

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Highly expressed in sinusoidal endothelial cells of liver, spleen and lymph nodes. Also expressed in non SEC-cells such as HMDMs (monocyte-derivedmacrophages), HAMs (T-cell leukemia virus type 1-associated myelopathy), and several macrophage cell line.

Post-translational modifications. Glycosylated. Proteolytically processed to yield a 190 kDa protein.

Domain organisation. Recognizes phosphatidyl serine via its epidermal growth factor-like domains.

RefSeq proteins (1): NP_060034* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000538	Link_dom	Domain
IPR000742	EGF	Domain
IPR000782	FAS1_domain	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002049	LE_dom	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR024731	NELL2-like_EGF	Domain
IPR036378	FAS1_dom_sf	Homologous_superfamily
IPR056806	EGF_STAB1-2	Domain

Pfam: PF00193, PF02469, PF12947, PF24887

UniProt features (163 total): disulfide bond 63, glycosylation site 28, domain 27, sequence conflict 12, sequence variant 9, strand 7, helix 6, chain 2, topological domain 2, region of interest 2, signal peptide 1, turn 1, compositionally biased region 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5N86	X-RAY DIFFRACTION	1.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWQ8-F1	70.62	0.02

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): 2497

Disulfide bonds (63): 1436–1446, 1440–1456, 1458–1469, 1475–1488, 1482–1498, 1500–1511, 1517–1530, 1524–1540, 1542–1553, 1559–1572, 1566–1582, 1962–1976, 1970–1986, 1988–1997, 2009–2020, 2014–2030, 2032–2041, 2051–2061, 2055–2067, 2069–2080 …

Glycosylation sites (28): 133, 337, 449, 619, 720, 761, 847, 925, 1016, 1028, 1100, 1247, 1275, 1367, 1429, 1437, 1465, 1573, 1679, 1743 …

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-2142845	Hyaluronan metabolism
R-HSA-2160916	Hyaluronan degradation
R-HSA-3000497	Scavenging by Class H Receptors
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656	Vesicle-mediated transport
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 141 (showing top): ATACCTC_MIR202, GOBP_HYALURONAN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_HYALURONAN_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, GOBP_BLOOD_VESSEL_MORPHOGENESIS, CAIRO_HEPATOBLASTOMA_DN

GO Biological Process (7): angiogenesis (GO:0001525), endocytosis (GO:0006897), receptor-mediated endocytosis (GO:0006898), cell adhesion (GO:0007155), hyaluronan catabolic process (GO:0030214), defense response to bacterium (GO:0042742), defense response to Gram-positive bacterium (GO:0050830)

GO Molecular Function (8): low-density lipoprotein particle receptor activity (GO:0005041), scavenger receptor activity (GO:0005044), calcium ion binding (GO:0005509), hyaluronic acid binding (GO:0005540), protein-disulfide reductase activity (GO:0015035), low-density lipoprotein particle binding (GO:0030169), protein binding (GO:0005515), cargo receptor activity (GO:0038024)

GO Cellular Component (6): cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endocytic vesicle membrane (GO:0030666), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Glycosaminoglycan metabolism	1
Hyaluronan metabolism	1
Binding and Uptake of Ligands by Scavenger Receptors	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Vesicle-mediated transport	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
vesicle-mediated transport	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
endocytosis	1
cellular process	1
glycosaminoglycan catabolic process	1
hyaluronan metabolic process	1
defense response	1
response to bacterium	1
defense response to bacterium	1
low-density lipoprotein particle binding	1
lipoprotein particle receptor activity	1
cargo receptor activity	1
metal ion binding	1
carboxylic acid binding	1
disulfide oxidoreductase activity	1
catalytic activity, acting on a protein	1
lipoprotein particle binding	1
binding	1
molecular_function	1
molecular adaptor activity	1
cytoplasm	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

874 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAB2	ADGRB1	O14514	862
STAB2	GULP1	Q9UBP9	856
STAB2	TIMD4	Q96H15	820
STAB2	ALB	P02768	761
STAB2	CD44	P16070	752
STAB2	LYVE1	Q9Y5Y7	743
STAB2	HMMR	O75330	711
STAB2	CLEC4M	Q9H2X3	710
STAB2	SCARA5	Q6ZMJ2	686
STAB2	DOCK1	Q14185	683
STAB2	MFGE8	Q08431	668
STAB2	ADGRB3	O60242	665
STAB2	ELMO1	Q92556	632
STAB2	VWF	P04275	613
STAB2	STXBP5	Q5T5C0	607

IntAct

7 interactions, top by confidence:

A	B	Type	Score
Tmsb4x	STAB2	psi-mi:“MI:0915”(physical association)	0.590
STAB2	NPM1	psi-mi:“MI:0915”(physical association)	0.400
STAB2	TMSB4X	psi-mi:“MI:0915”(physical association)	0.370
VPS35	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): STAB2 (Affinity Capture-Western), STAB2 (Affinity Capture-Western), ITGB5 (Affinity Capture-Western), ITGB5 (FRET), STAB2 (Proximity Label-MS), STAB2 (Cross-Linking-MS (XL-MS)), STAB2 (Protein-peptide), STAB2 (Affinity Capture-Western), STAB2 (Affinity Capture-Western), MAPK3 (Affinity Capture-Western), MAPK1 (Affinity Capture-Western), STAB2 (Affinity Capture-Western), STAB2 (Affinity Capture-Western)

ESM2 similar proteins: A0A1D0C023, A5Z1X6, B0FYY4, C0K3N4, D3GGZ8, D5FM37, G5ECE3, G5ECS8, G5EGM1, O18016, O64758, O73682, O76840, O77469, O77636, P08479, P0DRJ0, P11584, P24348, P33434, P33436, P49134, P53712, P78536, P81439, P84032, P98060, P98092, Q00174, Q04833, Q06561, Q11101, Q19204, Q19267, Q21313, Q27591, Q7Z1K3, Q811M5, Q8L7E3, Q8R4U0

Diamond homologs: A0A182C2Z2, C6KFA3, F1RWC3, O08628, O08859, O14594, O14786, O35276, O35375, O43897, O57382, O57460, O60462, O60494, O70244, P03994, P07354, P07897, P07898, P10859, P10915, P13497, P13608, P13611, P14745, P16112, P25723, P28824, P42674, P55066, P55067, P55252, P79795, P97333, P98063, P98065, P98066, P98068, P98069, P98070

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	284
Likely benign	38
Benign	21

Top pathogenic / likely-pathogenic (0)

SpliceAI

9274 predictions. Top by Δscore:

Variant	Effect	Δscore
12:103631596:A:AG	acceptor_gain	1.0000
12:103631597:G:GG	acceptor_gain	1.0000
12:103631692:GC:G	donor_gain	1.0000
12:103637105:A:AG	acceptor_gain	1.0000
12:103637106:T:G	acceptor_gain	1.0000
12:103637106:T:TA	acceptor_gain	1.0000
12:103637106:TGCA:T	acceptor_loss	1.0000
12:103637109:A:AG	acceptor_gain	1.0000
12:103637109:A:C	acceptor_loss	1.0000
12:103637110:G:GA	acceptor_gain	1.0000
12:103637110:GC:G	acceptor_gain	1.0000
12:103637110:GCC:G	acceptor_gain	1.0000
12:103637110:GCCA:G	acceptor_gain	1.0000
12:103637110:GCCAT:G	acceptor_gain	1.0000
12:103637232:CGACC:C	donor_gain	1.0000
12:103637233:GACC:G	donor_gain	1.0000
12:103637233:GACCG:G	donor_gain	1.0000
12:103637234:ACC:A	donor_gain	1.0000
12:103637234:ACCGT:A	donor_loss	1.0000
12:103637235:CC:C	donor_gain	1.0000
12:103637235:CCGTG:C	donor_loss	1.0000
12:103637236:CGTG:C	donor_loss	1.0000
12:103637237:G:GG	donor_gain	1.0000
12:103637237:GT:G	donor_loss	1.0000
12:103637238:T:G	donor_loss	1.0000
12:103637239:GAG:G	donor_loss	1.0000
12:103638002:T:A	acceptor_gain	1.0000
12:103640111:T:TA	acceptor_gain	1.0000
12:103640116:A:AG	acceptor_gain	1.0000
12:103640118:T:A	acceptor_gain	1.0000

AlphaMissense

16799 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:103715865:T:A	C1530S	0.994
12:103715866:G:C	C1530S	0.994
12:103755329:T:A	W2248R	0.994
12:103755329:T:C	W2248R	0.994
12:103755331:G:C	W2248C	0.994
12:103755331:G:T	W2248C	0.994
12:103755454:C:G	C2289W	0.993
12:103712437:T:A	C1469S	0.992
12:103712438:G:C	C1469S	0.992
12:103594494:G:C	W105C	0.991
12:103594494:G:T	W105C	0.991
12:103685064:T:A	C993S	0.991
12:103685065:G:C	C993S	0.991
12:103712416:T:C	F1462L	0.991
12:103712418:C:A	F1462L	0.991
12:103712418:C:G	F1462L	0.991
12:103750630:T:A	C2164S	0.991
12:103750631:G:C	C2164S	0.991
12:103750699:T:A	C2187S	0.991
12:103750700:G:C	C2187S	0.991
12:103755452:T:C	C2289R	0.991
12:103715847:T:A	C1524S	0.990
12:103715848:G:C	C1524S	0.990
12:103717815:T:A	C1553S	0.990
12:103717816:G:C	C1553S	0.990
12:103724987:T:A	C1566S	0.990
12:103724988:G:C	C1566S	0.990
12:103750681:T:A	C2181S	0.990
12:103750682:G:C	C2181S	0.990
12:103753337:T:C	L2233P	0.990

dbSNP variants (sampled 300 via entrez): RS1000057591 (12:103643815 G>A,C), RS1000063926 (12:103683734 G>A,T), RS1000105120 (12:103598825 C>A,G,T), RS1000131443 (12:103646401 T>C,G), RS1000132209 (12:103682422 C>A,T), RS1000151980 (12:103606908 C>T), RS1000173026 (12:103762970 C>T), RS1000191149 (12:103603755 T>C), RS1000194562 (12:103682927 G>A), RS1000218075 (12:103679019 A>G), RS1000219527 (12:103599050 T>C), RS1000222866 (12:103633606 C>T), RS1000223574 (12:103716836 G>A,C), RS1000227886 (12:103627188 G>A), RS1000256487 (12:103610895 T>G)

Disease associations

OMIM: gene MIM:608561 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000627_3	vWF levels	7.000000e-10
GCST001188_7	vWF and FVIII levels	3.000000e-06
GCST001214_1	Coronary restenosis	1.000000e-07
GCST002408_11	Response to methotrexate in juvenile idiopathic arthritis	4.000000e-06
GCST003174_11	Sense of smell	2.000000e-07
GCST003174_4	Sense of smell	3.000000e-07
GCST003210_4	Low vWF levels	1.000000e-08
GCST003518_89	Daytime sleep phenotypes	6.000000e-06
GCST004428_11	Stem cell growth factor beta levels	1.000000e-23
GCST007445_11	Factor VIII levels	1.000000e-17
GCST007445_14	Factor VIII levels	1.000000e-13
GCST007445_19	Factor VIII levels	1.000000e-13
GCST007445_22	Factor VIII levels	2.000000e-17
GCST007445_46	Factor VIII levels	3.000000e-20
GCST007445_50	Factor VIII levels	2.000000e-14
GCST007445_55	Factor VIII levels	2.000000e-14
GCST007445_58	Factor VIII levels	6.000000e-18
GCST007446_1	vWF levels	2.000000e-08
GCST007446_13	vWF levels	2.000000e-36
GCST007446_17	vWF levels	1.000000e-14
GCST007446_40	vWF levels	5.000000e-37
GCST007446_60	vWF levels	5.000000e-09
GCST007446_70	vWF levels	2.000000e-36
GCST007446_74	vWF levels	2.000000e-14
GCST007446_80	vWF levels	7.000000e-41
GCST009028_17	Adverse response to drug	2.000000e-08
GCST011493_2	Systemic lupus erythematosus	4.000000e-08
GCST011536_3	Intestinal permeability measurement	4.000000e-06
GCST012231_113	A body shape index	1.000000e-08
GCST90002393_424	Monocyte count	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004630	factor VIII measurement
EFO:0007828	daytime rest measurement
EFO:0009658	adverse effect
EFO:0011031	intestinal permeability measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	increases expression	1
titanium dioxide	increases expression	1
aflatoxin B2	increases methylation	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
Arsenic	decreases methylation, increases abundance	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Copper	affects cotreatment, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Oxygen	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	increases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Metals, Heavy	decreases methylation, increases abundance	1

Clinical trials (associated diseases)

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