STAMBP

Summary

STAMBP (STAM binding protein, HGNC:16950) is a protein-coding gene on chromosome 2p13.1, encoding STAM-binding protein (O95630). Zinc metalloprotease that specifically cleaves ‘Lys-63’-linked polyubiquitin chains. It is a selective cancer dependency (DepMap: 28.1% of cell lines).

Cytokine-mediated signal transduction in the JAK-STAT cascade requires the involvement of adaptor molecules. One such signal-transducing adaptor molecule contains an SH3 domain that is required for induction of MYC and cell growth. The protein encoded by this gene binds to the SH3 domain of the signal-transducing adaptor molecule, and plays a critical role in cytokine-mediated signaling for MYC induction and cell cycle progression. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene.

Source: NCBI Gene 10617 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly-capillary malformation syndrome (Definitive, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 220 total — 13 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 28.1% of screened cell lines
• MANE Select transcript: NM_213622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16950
Approved symbol	STAMBP
Name	STAM binding protein
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	AMSH
Ensembl gene	ENSG00000124356
Ensembl biotype	protein_coding
OMIM	606247
Entrez	10617

Gene structure

Transcript identifiers

Ensembl transcripts: 78 — 35 nonsense_mediated_decay, 30 protein_coding, 12 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000339566, ENST00000394070, ENST00000394073, ENST00000409707, ENST00000424659, ENST00000432295, ENST00000452725, ENST00000478946, ENST00000486458, ENST00000487811, ENST00000536064, ENST00000682105, ENST00000682157, ENST00000682271, ENST00000682329, ENST00000682351, ENST00000682352, ENST00000682379, ENST00000682387, ENST00000682423, ENST00000682558, ENST00000682592, ENST00000682683, ENST00000682747, ENST00000682784, ENST00000682799, ENST00000682847, ENST00000682848, ENST00000682851, ENST00000682998, ENST00000683016, ENST00000683027, ENST00000683036, ENST00000683149, ENST00000683205, ENST00000683247, ENST00000683304, ENST00000683314, ENST00000683317, ENST00000683349, ENST00000683391, ENST00000683408, ENST00000683417, ENST00000683434, ENST00000683465, ENST00000683518, ENST00000683530, ENST00000683582, ENST00000683594, ENST00000683718, ENST00000683728, ENST00000683818, ENST00000683852, ENST00000683877, ENST00000683902, ENST00000683928, ENST00000684095, ENST00000684174, ENST00000684200, ENST00000684312, ENST00000684321, ENST00000684337, ENST00000684355, ENST00000684426, ENST00000684585, ENST00000684671, ENST00000684697, ENST00000684703, ENST00000684716, ENST00000684758, ENST00000684774, ENST00000879042, ENST00000879043, ENST00000879044, ENST00000933900, ENST00000933901, ENST00000933902, ENST00000958034

RefSeq mRNA: 13 — MANE Select: NM_213622 NM_001353967, NM_001353968, NM_001353969, NM_001353970, NM_001353971, NM_001353972, NM_001353973, NM_001353974, NM_001353975, NM_001353976, NM_006463, NM_201647, NM_213622

CCDS: CCDS1929, CCDS92778, CCDS92779

Canonical transcript exons

ENST00000394070 — 10 exons

Exon	Start	End
ENSE00000761619	73844813	73844888
ENSE00000761622	73849363	73849487
ENSE00000761623	73850376	73850513
ENSE00001200513	73862203	73867168
ENSE00001517431	73828961	73829510
ENSE00003487057	73860052	73860151
ENSE00003554064	73845167	73845262
ENSE00003682679	73859254	73859366
ENSE00003683613	73847387	73847753
ENSE00003920832	73830845	73831059

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1781 / max 323.2787, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20961	18.8555	1809
20962	0.3225	136

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.16	gold quality
spinal cord	UBERON:0002240	96.84	gold quality
corpus callosum	UBERON:0002336	96.12	gold quality
inferior vagus X ganglion	UBERON:0005363	95.78	gold quality
calcaneal tendon	UBERON:0003701	95.55	gold quality
subthalamic nucleus	UBERON:0001906	94.63	gold quality
pons	UBERON:0000988	94.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.23	gold quality
sural nerve	UBERON:0015488	93.83	gold quality
gastrocnemius	UBERON:0001388	93.74	gold quality
muscle of leg	UBERON:0001383	93.70	gold quality
rectum	UBERON:0001052	93.51	gold quality
ventricular zone	UBERON:0003053	93.39	gold quality
tendon	UBERON:0000043	92.76	gold quality
ganglionic eminence	UBERON:0004023	92.74	gold quality
secondary oocyte	CL:0000655	92.64	gold quality
putamen	UBERON:0001874	92.55	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.53	gold quality
smooth muscle tissue	UBERON:0001135	92.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.43	gold quality
substantia nigra	UBERON:0002038	92.42	gold quality
amygdala	UBERON:0001876	92.39	gold quality
midbrain	UBERON:0001891	92.39	gold quality
islet of Langerhans	UBERON:0000006	92.33	gold quality
colonic epithelium	UBERON:0000397	92.22	gold quality
hypothalamus	UBERON:0001898	92.21	gold quality
lower esophagus mucosa	UBERON:0035834	92.19	gold quality
muscle organ	UBERON:0001630	92.17	gold quality
middle frontal gyrus	UBERON:0002702	92.16	gold quality
superior vestibular nucleus	UBERON:0007227	92.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.90
E-MTAB-6142	no	177.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting STAMBP, 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-4692	100.00	67.32	2066
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-378A-5P	99.65	66.33	1311

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 32)

• AMSH is a deubiquitinating enzyme with functions at the endosome to oppose ubiquitin-dependent receptor sorting (PMID:15314065)
• The cellular functions of UBPY are complex but clearly distinct from those of the Lys-63-ubiquitin-specific protease, AMSH, with which it shares a binding site on the SH3 domain of STAM (PMID:16520378)
• AMSH and AMSH-LP are anchored on the early endosomal membrane via interaction with the clathrin coat (PMID:16716190)
• AMSH has a role in the deubiquitination of the endosomal cargo preceding lysosomal degradation (PMID:16760479)
• AMSH, which has been recently characterized as a regulator of the endosomal sorting of epidermal growth factor receptor, represents a novel modulator of CaR signaling. (PMID:16854379)
• both the deubiquitination enzyme activity of AMSH and its CHMP3-binding ability are required to clear ubiquitinated cargo from endosomes (PMID:17159328)
• Endosomal AMSH (STAMBP) is a functional component of the multivesicular body pathway. (PMID:17261583)
• UBPY MIT domain and another ubiquitin isopeptidase, AMSH, reveals common interactions with CHMP1A and CHMP1B but a distinct selectivity of AMSH for CHMP3/VPS24, a core subunit of the ESCRT-III complex, and UBPY for CHMP7. (PMID:17711858)
• crystal structures of the human AMSH-LP DUB domain alone and in complex with a Lys 63-linked di-ubiquitin at 1.2 A and 1.6 A resolutions, respectively (PMID:18758443)
• Data suggest that AMSH and UBPY are essential for trafficking and down-regulation of PAR(2) but not for regulating PAR(2) dissociation from beta-arrestin2 or PAR(2)-mediated ERK2 activation. (PMID:19684015)
• AMSH interacts with ESCRT-0 to regulate the stability and trafficking of CXCR4. (PMID:20159979)
• Studies indicate that USP8/Ubpy and AMSH interact with ESCRT components to modulate the ubiquitination status of receptors and relevant sorting proteins. (PMID:21448666)
• tight coupling of ESCRT-III CHMP3 and AMSH functions and provide insight into the regulation of ESCRT-III (PMID:21827950)
• AMSH efficiently removes ubiquitin from the activated EGFR. (PMID:22800866)
• Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. (PMID:23542699)
• Recognition of the proximal ubiquitin is imperative for the linkage specificity and catalytic efficiency of AMSH. (PMID:24151880)
• associated molecule with the SH3 domain of STAM-mediated deubiquitination of connexin 43 protects Gap junctions from degradation (PMID:25070368)
• Two siblings with classic features of MIC-CAP syndrome that harbor a novel predicted splice mutation in STAMBP (PMID:25692795)
• The VHS domain of STAM2 directs AMSH to cleave longer Lys63-linked ubiquitin chains (PMID:26601948)
• The authors propose a structural organization where the AMSH-SH3 binding motif interacts with the STAM2-SH3 domain and contributes to the correct positioning of AMSH prior to polyubiquitin chains’ cleavage. (PMID:27725184)
• Targeting the deubiquitinase STAMBP inhibits NALP7 inflammasome activity. (PMID:28492230)
• Contrary to previously reported STAMBP mutations, the Ser236Phe mutation did not lead to constitutive activation of the PI3K-AKT-mTOR pathway in patient-derived LCLs, as indicated by the expression of phosphorylated S6 ribosomal protein, suggesting that it is not the major pathomechanism underlying the disorder in this patient. (PMID:29907875)
• these results indicate the importance of STAMBP in melanoma metastasis by regulating SLUG. (PMID:30454887)
• the present study reported the first case of a Chinese patient with refractory epilepsy as an initial symptom of MIC-CAP. Additionally, novel pathogenic compound heterozygosity of the STAMBP was identified. (PMID:31638258)
• Prediagnostic circulating inflammation biomarkers and esophageal squamous cell carcinoma: A case-cohort study in Japan. (PMID:31671219)
• The deubiquitinase STAMBP modulates cytokine secretion through the NLRP3 inflammasome. (PMID:33253913)
• STAMBP promotes lung adenocarcinoma metastasis by regulating the EGFR/MAPK signaling pathway. (PMID:34102455)
• Structural and functional characterization of ubiquitin variant inhibitors for the JAMM-family deubiquitinases STAMBP and STAMBPL1. (PMID:34425109)
• STAM binding protein regulated by hsa_circ_0007334 exerts oncogenic potential in pancreatic cancer. (PMID:36089485)
• The expression and clinical significance of STAMBP in breast cancer. (PMID:36309616)
• The deubiquitinating enzyme STAMBP is a newly discovered driver of triple-negative breast cancer progression that maintains RAI14 protein stability. (PMID:36434041)
• Identification of STAM-binding protein as a target for the treatment of gemcitabine resistance pancreatic cancer in a nutrient-poor microenvironment. (PMID:39242557)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stambpa	ENSDARG00000054501
danio_rerio	stambpb	ENSDARG00000086906
mus_musculus	Stambp	ENSMUSG00000006906
rattus_norvegicus	Stambp	ENSRNOG00000012227
drosophila_melanogaster	CG2224	FBGN0039773

Paralogs (1): STAMBPL1 (ENSG00000138134)

Protein

Protein identifiers

STAM-binding protein — O95630 (reviewed: O95630)

Alternative names: Associated molecule with the SH3 domain of STAM, Endosome-associated ubiquitin isopeptidase

All UniProt accessions (21): A0A140VK54, A0A804HHU9, A0A804HHV2, A0A804HI64, A0A804HIF8, A0A804HII8, A0A804HIJ2, A0A804HIV0, A0A804HJ64, A0A804HJC8, A0A804HJD9, A0A804HJE8, A0A804HJS0, A0A804HKA6, O95630, A0A804HKL2, A0A804HL27, A0A804HL38, C9JEK5, C9JK83, F5H5B9

UniProt curated annotations — full annotation on UniProt →

Function. Zinc metalloprotease that specifically cleaves ‘Lys-63’-linked polyubiquitin chains. Does not cleave ‘Lys-48’-linked polyubiquitin chains. Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization. Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways.

Subunit / interactions. Interacts with STAM. Interacts with SMAD6 and SMAD7. Interacts with CHMP3; the interaction appears to relieve the autoinhibition of CHMP3. Interacts with SMURF2 and RNF11; this interaction promotes ubiquitination.

Subcellular location. Nucleus. Membrane. Cytoplasm. Early endosome.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated after BMP type I receptor activation. Ubiquitinated by SMURF2 in the presence of RNF11.

Disease relevance. Microcephaly-capillary malformation syndrome (MICCAP) [MIM:614261] A congenital disorder characterized by severe progressive microcephaly, early-onset refractory epilepsy, profound developmental delay, and multiple small capillary malformations spread diffusely on the body. Additional more variable features include dysmorphic facial features, distal limb abnormalities, and mild heart defects. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by N-ethylmaleimide. Strongly and specifically inhibited by ubiquitin variants UbV(SP.2) and UbV(SP.3). Also inhibited by UbV(SP.1); an ubiquitin variant that also inhibits STAMBPL1.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Domain organisation. The JAMM motif is essential for the protease activity.

Miscellaneous. X-ray crystallography studies of STAMBPL1, another member of the peptidase M67C family, has shown that Glu-280 binds zinc indirectly via a water molecule. Nevertheless, this residue is essential for catalytic activity.

Similarity. Belongs to the peptidase M67C family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95630-1	1	yes
O95630-2	2

RefSeq proteins (13): NP_001340896, NP_001340897, NP_001340898, NP_001340899, NP_001340900, NP_001340901, NP_001340902, NP_001340903, NP_001340904, NP_001340905, NP_006454, NP_964010, NP_998787* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000555	JAMM/MPN+_dom	Domain
IPR015063	USP8_dimer	Domain
IPR037518	MPN	Domain
IPR044098	STAMBP/STALP-like_MPN	Domain

Pfam: PF01398, PF08969

UniProt features (50 total): strand 12, helix 10, binding site 7, sequence variant 6, modified residue 5, region of interest 2, turn 2, chain 1, domain 1, site 1, splice variant 1, mutagenesis site 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3RZV	X-RAY DIFFRACTION	1.67
2XZE	X-RAY DIFFRACTION	1.75
3RZU	X-RAY DIFFRACTION	2.5
9LE4	X-RAY DIFFRACTION	2.6
5IXF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95630-F1	84.75	0.66

Functional residue map

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

Catalytic / active sites (1): 280 (indirect zinc-binding)

Ligand- & substrate-binding residues (7): 396; 398; 335; 337; 348; 350; 390

Post-translational modifications (5): 2, 48, 243, 245, 247

Mutagenesis-validated functional residues (1):

Position	Phenotype
348	promotes accumulation of ubiquitin on endosomes, ablates enzymatic activity toward polyubiquitin substrate and allows ub

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5689901	Metalloprotease DUBs
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 256 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, AAGCCAT_MIR135A_MIR135B, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_CYTOKINESIS, GOBP_NEGATIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (10): mitotic cytokinesis (GO:0000281), proteolysis (GO:0006508), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), positive regulation of cell population proliferation (GO:0008284), protein deubiquitination (GO:0016579), negative regulation of Ras protein signal transduction (GO:0046580), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), protein K63-linked deubiquitination (GO:0070536), hippocampal neuron apoptotic process (GO:0110088), negative regulation of hippocampal neuron apoptotic process (GO:0110091)

GO Molecular Function (9): protein domain specific binding (GO:0019904), metal ion binding (GO:0046872), K63-linked deubiquitinase activity (GO:0061578), deubiquitinase activity (GO:0101005), metal-dependent deubiquitinase activity (GO:0140492), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), endosome (GO:0005768), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), cleavage furrow (GO:0032154), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Deubiquitination	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
deubiquitinase activity	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
protein metabolic process	1
cell surface receptor signaling pathway via STAT	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
protein deubiquitination	1
neuron apoptotic process	1
negative regulation of neuron apoptotic process	1
hippocampal neuron apoptotic process	1
regulation of hippocampal neuron apoptotic process	1
protein binding	1
cation binding	1
ubiquitin-like protein peptidase activity	1
metallopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
endomembrane system	1
cytoplasmic vesicle	1
endosome	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

3220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAMBP	STAM2	O75886	996
STAMBP	STAM	Q92783	979
STAMBP	CHMP3	Q9Y3E7	974
STAMBP	A0A140T963	A0A140T963	974
STAMBP	CHMP1B	Q7LBR1	923
STAMBP	CHMP2A	O43633	922
STAMBP	COPS5	Q92905	828
STAMBP	RNF11	Q9Y3C5	827
STAMBP	USP8	P40818	824
STAMBP	SMURF2	Q9HAU4	821
STAMBP	CHMP1A	Q9HD42	796
STAMBP	ZUP1	Q96AP4	753
STAMBP	UCHL5	Q9Y5K5	723
STAMBP	CHMP6	Q96FZ7	720
STAMBP	KNSTRN	Q9Y448	716

IntAct

185 interactions, top by confidence:

A	B	Type	Score
STAMBP	CHMP1B	psi-mi:“MI:0915”(physical association)	0.960
STAMBP	CHMP3	psi-mi:“MI:0915”(physical association)	0.960
CHMP1B	STAMBP	psi-mi:“MI:0915”(physical association)	0.960
CHMP3	STAMBP	psi-mi:“MI:0915”(physical association)	0.960
CHMP1B	STAMBP	psi-mi:“MI:0403”(colocalization)	0.960
CHMP3	STAMBP	psi-mi:“MI:0403”(colocalization)	0.960
STAMBP	CHMP1B	psi-mi:“MI:0407”(direct interaction)	0.960
CHMP3	STAMBP	psi-mi:“MI:2364”(proximity)	0.960

BioGRID (259): STAMBP (Two-hybrid), CHMP3 (Two-hybrid), CHMP1B (Two-hybrid), STAMBP (Affinity Capture-MS), STAMBP (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), GRB2 (Affinity Capture-MS), CHMP3 (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), PIK3C2A (Affinity Capture-MS), GAK (Affinity Capture-MS), STAMBP (Affinity Capture-MS), STAMBP (Two-hybrid), STAMBP (Two-hybrid), STAMBP (Reconstituted Complex)

ESM2 similar proteins: A0A8M3B525, A2AHJ4, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E1C3P4, E9Q4Z2, O00763, O42611, O94967, O95630, P46736, P46737, P48553, Q15386, Q15542, Q3TLI0, Q4VA72, Q5KSL6, Q5R558, Q5R9L6, Q5RAQ5, Q5VVJ2, Q641K1, Q66GV6, Q66H62, Q69Z66, Q6RI45, Q6WKZ8, Q76N33, Q7M757, Q80U95, Q8BPM2, Q8CGF6, Q8IVH8, Q8QFR2, Q8TAT6, Q8VDD9, Q8W206

Diamond homologs: O95630, Q54Q40, Q5PNU3, Q5R558, Q63ZM7, Q6NKP9, Q6TH47, Q76N33, Q8R424, Q8VYB5, Q96FJ0, Q9CQ26, Q9P371, O94454, P41883, Q4IJM4, Q6BMQ3, Q6FKS1, Q6FT36, Q750E9, Q7RXX8, Q86IJ1, P41878, O00487, O35593, P43588, Q5BBF1, Q8SQY3, Q9LT08, O76577, Q9V3H2

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
SMURF2	“down-regulates quantity by destabilization”	STAMBP	polyubiquitination
RNF11	“down-regulates quantity by destabilization”	STAMBP	binding
BMPR1B	“up-regulates activity”	STAMBP	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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
Endosomal Sorting Complex Required For Transport (ESCRT)	11	101.3×	8e-18
InlB-mediated entry of Listeria monocytogenes into host cell	5	95.2×	9e-08
Budding and maturation of HIV virion	9	91.8×	4e-14
Late endosomal microautophagy	8	65.3×	4e-11
Negative regulation of MET activity	5	64.9×	7e-07
Pyroptosis	5	52.9×	2e-06
EGFR downregulation	5	43.3×	4e-06
Sealing of the nuclear envelope (NE) by ESCRT-III	5	43.3×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	8	136.7×	2e-14
late endosome to lysosome transport	8	136.7×	2e-14
viral budding via host ESCRT complex	9	124.5×	1e-15
multivesicular body sorting pathway	8	110.7×	1e-13
midbody abscission	8	101.1×	3e-13
regulation of mitotic spindle assembly	8	101.1×	3e-13
multivesicular body assembly	11	99.9×	2e-17
regulation of centrosome duplication	7	88.4×	3e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	7
Uncertain significance	85
Likely benign	64
Benign	23

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1034283	NM_213622.4(STAMBP):c.843_844del (p.Cys282fs)	Pathogenic
1366374	NM_213622.4(STAMBP):c.1214del (p.Phe405fs)	Pathogenic
1458642	NC_000002.11:g.(?74089310)(74089386_?)del	Pathogenic
2028025	NM_213622.4(STAMBP):c.487dup (p.His163fs)	Pathogenic
2425561	NC_000002.11:g.(?72359356)(74779761_?)del	Pathogenic
2425598	NC_000002.11:g.(?74087159)(74087298_?)del	Pathogenic
2637512	NM_213622.4(STAMBP):c.5_6dup (p.Asp3fs)	Pathogenic
420170	NM_213622.4(STAMBP):c.938C>T (p.Thr313Ile)	Pathogenic
436881	NM_213622.4(STAMBP):c.649C>T (p.Gln217Ter)	Pathogenic
492960	NM_213622.4(STAMBP):c.707C>T (p.Ser236Phe)	Pathogenic
503843	NM_213622.4(STAMBP):c.503_524del (p.Met168fs)	Pathogenic
50796	NM_213622.4(STAMBP):c.299T>A (p.Phe100Tyr)	Pathogenic
50797	NM_213622.4(STAMBP):c.411del (p.Ile138fs)	Pathogenic
1992771	NM_213622.4(STAMBP):c.868-1G>A	Likely pathogenic
212320	NM_213622.4(STAMBP):c.1119-6T>G	Likely pathogenic
2690758	NM_213622.4(STAMBP):c.1006-2A>T	Likely pathogenic
3767307	NM_213622.4(STAMBP):c.376-1G>A	Likely pathogenic
424114	NM_213622.4(STAMBP):c.932G>T (p.Cys311Phe)	Likely pathogenic
424125	NM_213622.4(STAMBP):c.230A>G (p.His77Arg)	Likely pathogenic
817554	NM_213622.4(STAMBP):c.232C>T (p.Arg78Ter)	Likely pathogenic

SpliceAI

2406 predictions. Top by Δscore:

Variant	Effect	Δscore
2:73830837:T:A	acceptor_gain	1.0000
2:73830841:TCA:T	acceptor_loss	1.0000
2:73830842:CAG:C	acceptor_loss	1.0000
2:73830843:A:AG	acceptor_gain	1.0000
2:73830843:AG:A	acceptor_loss	1.0000
2:73830844:G:GA	acceptor_gain	1.0000
2:73830844:GA:G	acceptor_gain	1.0000
2:73830844:GAA:G	acceptor_gain	1.0000
2:73830844:GAAC:G	acceptor_gain	1.0000
2:73830844:GAACT:G	acceptor_gain	1.0000
2:73831013:G:GT	donor_gain	1.0000
2:73831014:A:T	donor_gain	1.0000
2:73831051:G:GG	donor_gain	1.0000
2:73831060:G:GG	donor_gain	1.0000
2:73844807:CCTTA:C	acceptor_loss	1.0000
2:73844808:CTTA:C	acceptor_loss	1.0000
2:73844809:TTA:T	acceptor_loss	1.0000
2:73844810:TA:T	acceptor_loss	1.0000
2:73844811:A:AC	acceptor_loss	1.0000
2:73844811:A:AG	acceptor_gain	1.0000
2:73844812:G:GG	acceptor_gain	1.0000
2:73845152:T:A	acceptor_gain	1.0000
2:73845157:T:A	acceptor_gain	1.0000
2:73845159:T:TA	acceptor_gain	1.0000
2:73845165:A:AG	acceptor_gain	1.0000
2:73845166:G:GG	acceptor_gain	1.0000
2:73845166:GA:G	acceptor_gain	1.0000
2:73845166:GAA:G	acceptor_gain	1.0000
2:73845166:GAAA:G	acceptor_gain	1.0000
2:73845166:GAAAT:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000035714 (2:73858292 C>A), RS1000075425 (2:73832570 A>C,G), RS1000262832 (2:73868984 G>A), RS1000345445 (2:73856907 C>T), RS1000376276 (2:73863050 T>C), RS1000502999 (2:73845672 C>T), RS1000552793 (2:73832816 C>T), RS1000569649 (2:73850659 C>A,G,T), RS1000586538 (2:73857138 C>T), RS1000640183 (2:73845364 G>C,T), RS1000662919 (2:73852187 G>C), RS1000669799 (2:73843809 A>G), RS1000702333 (2:73844021 A>T), RS1000721845 (2:73858893 C>A,T), RS1000975784 (2:73832572 G>GATATAC)

Disease associations

OMIM: gene MIM:606247 | disease phenotypes: MIM:614261, MIM:606056

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly-capillary malformation syndrome	Definitive	Autosomal recessive

Mondo (2): microcephaly-capillary malformation syndrome (MONDO:0013659), MOGS-congenital disorder of glycosylation (MONDO:0011629)

Orphanet (2): Microcephaly-capillary malformation syndrome (Orphanet:294016), MOGS-CDG (Orphanet:79330)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000175	Cleft palate
HP:0000253	Progressive microcephaly
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000340	Sloping forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000508	Ptosis
HP:0000648	Optic atrophy
HP:0001156	Brachydactyly
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001285	Spastic tetraparesis
HP:0001290	Generalized hypotonia
HP:0001336	Myoclonus
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001655	Patent foramen ovale
HP:0001667	Right ventricular hypertrophy
HP:0001792	Small nail
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0003196	Short nose
HP:0003429	CNS hypomyelination

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST005025_21	Anti-saccade response	1.000000e-06
GCST005025_7	Anti-saccade response	3.000000e-06
GCST006249_93	Serum metabolite levels	8.000000e-29
GCST006879_11	Blood metabolite levels	1.000000e-12
GCST006879_6	Blood metabolite levels	5.000000e-14
GCST006879_7	Blood metabolite levels	2.000000e-15
GCST006879_9	Blood metabolite levels	2.000000e-14
GCST011354_24	Bell’s palsy	5.000000e-06
GCST012020_44	Serum metabolite levels	3.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006874	antisaccade response measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565264	Congenital Disorder Of Glycosylation, Type IIB (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105848 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Capzimin	IC50	340 nM	US-10005735: Inhibitors of RPN11

ChEMBL bioactivities

20 potent at pChembl≥5 of 22 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.48	IC50	330	nM	CHEMBL4586347
6.30	IC50	500	nM	CHEMBL4104719
6.22	IC50	600	nM	CHEMBL4096289
6.05	IC50	900	nM	CHEMBL4088568
6.05	IC50	900	nM	CHEMBL4080490
6.05	IC50	900	nM	CHEMBL4095913
5.89	IC50	1300	nM	CHEMBL4100384
5.89	IC50	1300	nM	CHEMBL4105598
5.77	IC50	1700	nM	CHEMBL4099434
5.77	IC50	1700	nM	CHEMBL4078891
5.66	IC50	2200	nM	CHEMBL4086748
5.46	IC50	3500	nM	CHEMBL4080694
5.46	IC50	3500	nM	CHEMBL4069023
5.46	IC50	3500	nM	CHEMBL4083926
5.39	IC50	4100	nM	CHEMBL4103171
5.35	IC50	4500	nM	CHEMBL4073553
5.33	IC50	4700	nM	CHEMBL4070821
5.30	IC50	5000	nM	CHEMBL4065318
5.17	IC50	6800	nM	CHEMBL4091693
5.11	IC50	7800	nM	CHEMBL4093962

PubChem BioAssay actives

22 with measured affinity, of 29 total; 22 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(1,3-benzodioxol-5-ylmethyl)-8-[[3-(1,3-benzodioxol-5-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	0.2000	uM
N-(furan-2-ylmethyl)-2-[6-morpholin-4-yl-4-oxo-3-(2-phenylethyl)quinazolin-2-yl]sulfanylacetamide	1558726: Inhibition of human STAMBP expressed in Sf21 cells pre-incubated for 20 mins before Ubiquitinated NALP7 substrate addition and measured after 1 hr by immunoblotting analysis	ic50	0.3300	uM
N-(pyridin-4-ylmethyl)-8-[[3-(pyridin-4-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	0.5000	uM
N-[(4-methoxyphenyl)methyl]-8-[[3-[(4-methoxyphenyl)methylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	0.6000	uM
N-(furan-2-ylmethyl)-8-[[3-(furan-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	0.9000	uM
N-[(4-fluorophenyl)methyl]-8-[[3-[(4-fluorophenyl)methylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	0.9000	uM
8-[[3-[(4-morpholin-4-ylphenyl)methylcarbamoyl]quinolin-8-yl]disulfanyl]-N-[(4-piperidin-1-ylphenyl)methyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	0.9000	uM
N-(2-thiophen-2-ylethyl)-8-[[3-(2-thiophen-2-ylethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	1.3000	uM
N-(thiophen-2-ylmethyl)-8-[[3-(thiophen-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	1.3000	uM
N-[2-(furan-2-yl)ethyl]-8-[[3-[2-(furan-2-yl)ethylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	1.7000	uM
8-[(3-carbamoylquinolin-8-yl)disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	1.7000	uM
methyl 2-[[8-[[3-[(2-methoxy-2-oxoethyl)carbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carbonyl]amino]acetate	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	2.2000	uM
N-(pyridin-3-ylmethyl)-8-[[3-(pyridin-3-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	3.5000	uM
N-[[4-(trifluoromethyl)phenyl]methyl]-8-[[3-[[4-(trifluoromethyl)phenyl]methylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	3.5000	uM
benzyl 2-[[2-[[8-[[3-[[2-oxo-2-[(2-oxo-2-phenylmethoxyethyl)amino]ethyl]carbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carbonyl]amino]acetyl]amino]acetate	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	3.5000	uM
N-methyl-8-[[3-(methylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	4.1000	uM
8-sulfanyl-N-[2-(1,3-thiazol-2-yl)ethyl]quinoline-3-carboxamide	1802702: In Vitro AMSH Activity Assay from Article 10.1038/nchembio.2326: “Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11.”	ic50	4.5000	uM
N-[2-(1,3-thiazol-2-yl)ethyl]-8-[[3-[2-(1,3-thiazol-2-yl)ethylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	4.5000	uM
N-(1,3-thiazol-2-yl)-8-[[3-(1,3-thiazol-2-ylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	4.7000	uM
N-(1,3-oxazol-2-yl)-8-[[3-(1,3-oxazol-2-ylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	5.0000	uM
N-(oxolan-2-ylmethyl)-8-[[3-(oxolan-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	6.8000	uM
N-(1,3-thiazol-2-ylmethyl)-8-[[3-(1,3-thiazol-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480596: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	ic50	7.8000	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
methacrylaldehyde	increases oxidation, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
PF 3758309	decreases expression	1
Rosiglitazone	decreases expression	1
Acrolein	affects cotreatment, increases oxidation	1
Aspirin	increases expression	1
Diethylstilbestrol	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases oxidation	1
Valproic Acid	decreases methylation	1
Isotretinoin	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Asbestos, Serpentine	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4049711	Binding	Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay	Discovery of an Inhibitor of the Proteasome Subunit Rpn11. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B2HG	Abcam HeLa STAMBP KO	Cancer cell line	Female
CVCL_C6TG	WAe001-A-95	Embryonic stem cell	Male
CVCL_TQ54	HAP1 STAMBP (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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