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): 225 total — 13 pathogenic, 7 likely-pathogenic
• GTEx eGene: eQTL in 40 tissues, sQTL in 36 (q < 0.05)
• Phenotypes (HPO): 42
• Cancer dependency (DepMap): dependent in 28.1% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.83 (unconstrained)
• MANE Select transcript: NM_213622
• Interaction hub: 1,718 STRING partners (top 10% of genes corpus-wide)

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: 90 — 44 nonsense_mediated_decay, 33 protein_coding, 12 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000394070

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 4, TSL 4: 1, TSL 5: 4

ENST00000394070, ENST00000339566, 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, ENST00000973605, ENST00001039018, ENST00001039019, ENST00001039020, ENST00001039021, ENST00001039023, ENST00001080696, ENST00001080697, ENST00001080698, ENST00001080699, ENST00001128095, ENST00001128096

RefSeq mRNA: 17 — 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_001438900, NM_001438901, NM_001438902, NM_001438903, 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.

Highest expression (Bgee): C1 segment of cervical spinal cord, spinal cord, corpus callosum, inferior vagus X ganglion, calcaneal tendon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

STAMBP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 40 tissues and its splicing (sQTL) in 36 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 76 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	7.1e-71	+2.31	2:73860202:A:G
Skin Sun Exposed Lower leg	sqtl	7.5e-39	+0.72	2:73836546:T:C
Cells Cultured fibroblasts	sqtl	9.0e-38	+0.81	2:73836546:T:C
Nerve Tibial	sqtl	7.4e-32	-0.71	2:73836546:T:C
Adipose Subcutaneous	eqtl	8.6e-32	+0.39	2:73831767:G:T
Esophagus Mucosa	sqtl	2.5e-31	+0.78	2:73836546:T:C
Thyroid	sqtl	7.0e-30	+0.68	2:73836546:T:C
Skin Sun Exposed Lower leg	eqtl	4.2e-28	+0.34	2:73874206:A:G
Adipose Subcutaneous	sqtl	5.8e-28	+0.65	2:73836546:T:C
Skin Not Sun Exposed Suprapubic	sqtl	9.4e-24	+0.61	2:73836546:T:C
Artery Tibial	eqtl	9.6e-24	+0.31	2:73836546:T:C
Whole Blood	eqtl	1.7e-22	+0.23	2:73829437:A:G
Esophagus Muscularis	sqtl	1.3e-21	-0.73	2:73843059:C:T
Nerve Tibial	eqtl	1.3e-20	+0.30	2:73844024:C:T
Breast Mammary Tissue	sqtl	1.8e-20	+0.69	2:73844024:C:T
Adipose Visceral Omentum	sqtl	7.1e-20	+0.62	2:73831767:G:T
Muscle Skeletal	sqtl	1.2e-18	-0.54	2:73836546:T:C
Artery Aorta	sqtl	1.5e-18	-0.77	2:73843059:C:T
Thyroid	eqtl	8.1e-18	+0.29	2:73827375:C:CTGT
Lung	sqtl	5.8e-16	-0.56	2:73836546:T:C

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 294 tissues 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
popliteal artery	UBERON:0002250	91.96	gold quality
tibial artery	UBERON:0007610	91.95	gold quality
esophagus mucosa	UBERON:0002469	91.93	gold quality
mucosa of stomach	UBERON:0001199	91.85	gold quality
caudate nucleus	UBERON:0001873	91.81	gold quality
medulla oblongata	UBERON:0001896	91.78	gold quality
nucleus accumbens	UBERON:0001882	91.77	gold quality
prefrontal cortex	UBERON:0000451	91.73	gold quality
gall bladder	UBERON:0002110	91.66	gold quality
aorta	UBERON:0000947	91.63	gold quality
vagina	UBERON:0000996	91.60	gold quality
descending thoracic aorta	UBERON:0002345	91.60	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.51	gold quality
mucosa of transverse colon	UBERON:0004991	91.47	gold quality
esophagus	UBERON:0001043	91.45	gold quality
epithelium of esophagus	UBERON:0001976	91.43	gold quality
cingulate cortex	UBERON:0003027	91.39	gold quality
medial globus pallidus	UBERON:0002477	91.38	gold quality
tibial nerve	UBERON:0001323	91.35	gold quality
anterior cingulate cortex	UBERON:0009835	91.33	gold quality
esophagus squamous epithelium	UBERON:0006920	91.32	gold quality
globus pallidus	UBERON:0001875	91.27	gold quality
hair follicle	UBERON:0002073	91.26	gold quality
thoracic aorta	UBERON:0001515	91.25	gold quality
ascending aorta	UBERON:0001496	91.18	gold quality
cerebellar hemisphere	UBERON:0002245	91.18	gold quality
cerebellar cortex	UBERON:0002129	91.17	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.12	gold quality
body of uterus	UBERON:0009853	91.03	gold quality
oviduct epithelium	UBERON:0004804	91.00	gold quality
right frontal lobe	UBERON:0002810	90.92	gold quality
lymph node	UBERON:0000029	90.90	gold quality
endothelial cell	CL:0000115	90.89	gold quality
ventral tegmental area	UBERON:0002691	90.86	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.80	gold quality
lower esophagus	UBERON:0013473	90.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.76	gold quality
Ammon’s horn	UBERON:0001954	90.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.72	gold quality
ectocervix	UBERON:0012249	90.71	gold quality
right atrium auricular region	UBERON:0006631	90.69	gold quality
central nervous system	UBERON:0001017	90.66	gold quality
fallopian tube	UBERON:0003889	90.66	gold quality
adrenal tissue	UBERON:0018303	90.59	gold quality
cerebellum	UBERON:0002037	90.58	gold quality
tonsil	UBERON:0002372	90.53	gold quality
right testis	UBERON:0004534	90.53	gold quality
brain	UBERON:0000955	90.46	gold quality
telencephalon	UBERON:0001893	90.46	gold quality
granulocyte	CL:0000094	90.40	gold quality
skin of abdomen	UBERON:0001416	90.40	gold quality
primary visual cortex	UBERON:0002436	90.40	gold quality
monocyte	CL:0000576	90.35	gold quality
forebrain	UBERON:0001890	90.35	gold quality
leukocyte	CL:0000738	90.31	gold quality
body of tongue	UBERON:0011876	90.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.28	gold quality
right coronary artery	UBERON:0001625	90.28	gold quality
oocyte	CL:0000023	90.26	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.26	gold quality
prostate gland	UBERON:0002367	90.20	gold quality
parotid gland	UBERON:0001831	90.19	gold quality
mononuclear cell	CL:0000842	90.17	gold quality
gluteal muscle	UBERON:0002000	90.13	gold quality
skin of leg	UBERON:0001511	90.11	gold quality
frontal pole	UBERON:0002795	90.11	gold quality
left testis	UBERON:0004533	90.11	gold quality
neocortex	UBERON:0001950	90.10	gold quality
occipital lobe	UBERON:0002021	90.10	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	33.0
Corpus callosum	tissue	31.4
Frontal cortex	tissue	28.1
Skeletal muscle	tissue	27.9	medium
Spinal cord	tissue	27.8
Medulla oblongata	tissue	24.5
Tongue	tissue	23.8
Midbrain	tissue	23.1
Substantia nigra	tissue	20.7
Thalamus	tissue	20.0
Superior colliculi	tissue	19.9
Pons	tissue	19.4
Putamen	tissue	17.5
Periaqueductal gray	tissue	17.2
Hippocampal formation	tissue	16.5
Ventral forebrain	tissue	16.5
Duodenum	tissue	16.3	high
Rectum	tissue	16.1	high
Septum	tissue	16.1
Esophagus	tissue	16.0	low
Hypothalamus	tissue	15.8
Parathyroid gland	tissue	15.7	medium
Colon	tissue	14.9	high
Kidney	tissue	14.5	high
Smooth muscle	tissue	14.4	medium
Tonsil	tissue	14.3	medium
Small intestine	tissue	14.1	high
Salivary gland	tissue	13.7	high
Thyroid gland	tissue	13.7	medium
Heart muscle	tissue	13.5	medium
Thymus	tissue	13.1
Stomach 1	tissue	13.0	high
Cerebellum	tissue	13.0	medium
Prostate	tissue	13.0	high
Cerebral cortex	tissue	12.8	high
Occipital cortex	tissue	12.8
Basal ganglia	tissue	12.6	medium
Olfactory bulb	tissue	12.3
Adipose tissue	tissue	12.1	low
Prefrontal cortex	tissue	11.9
Motor cortex	tissue	11.7
Amygdala	tissue	11.6
Ovary	tissue	11.5	medium
Endometrium 1	tissue	11.4	medium
Somatosensory cortex	tissue	11.4
Fallopian tube	tissue	11.3	high
Retrosplenial cortex	tissue	11.3
Entorhinal cortex	tissue	11.0
Retrosplenial and cingulate cortex	tissue	10.9
Lymph node	tissue	10.6	medium
Urinary bladder	tissue	10.6	high
Insular cortex	tissue	10.6
Breast	tissue	10.5	high
Epididymis	tissue	10.4	medium
Liver	tissue	10.4	medium
Locus coeruleus	tissue	10.3
Temporal cortex	tissue	10.3
Appendix	tissue	10.2	high
Placenta	tissue	9.9	medium
Cervix	tissue	9.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (31.4), Cerebellar white matter (30.8), Parieto-temporal junction (white matter) (29.6), Dorsal funiculus (white matter) (29.3), Lateral funiculus (white matter) (29.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting STAMBP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 126 miRNAs:

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

gnomAD constraint: pLI 3.86e-06, LOEUF 0.829, missense Z 1.22 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000394070 — one region, missense o/e 0.91. DepMap (CRISPR cell-line fitness): dependent in 28.1% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): TYK-nu (-2.403), RVH-421 (-2.168), HCC1954 (-2.001), Evsa-T (-1.987), SCC-9 (-1.891), DAN-G (-1.821), UM-UC7 (-1.794), KYAE-1 (-1.79), EW-7 (-1.783), DoTc2 4510 (-1.751), HCC1806 (-1.74), T3M-5 (-1.723), KON (-1.698), LN-340 (-1.696), GSS (-1.687).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1917777) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal cerebral cortex morphology	1
hippocampal neuron degeneration	1
blepharoptosis	1
increased startle reflex	1
limb grasping	1
postnatal growth retardation	1
shortened QT interval	1
lethality at weaning, complete penetrance	1
preweaning lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R558	98.6%	Diamond
Xenopus laevis	Q63ZM7	64.2%	Diamond
Arabidopsis thaliana	Q5PNU3	62.3%	Diamond
Schizosaccharomyces pombe 972h-	Q9P371	52.8%	Diamond
Dictyostelium discoideum	Q54Q40	52.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DGUOK-AS1	ncRNA	100874048
DGUOK	protein-coding	1716
ACTG2	protein-coding	72
C2orf78	protein-coding	388960
DUSP11	protein-coding	8446
TPRKB	protein-coding	51002

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, A0A804HKL2, A0A804HL27, A0A804HL38, C9JEK5, C9JK83, O95630, 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 (17): NP_001340896, NP_001340897, NP_001340898, NP_001340899, NP_001340900, NP_001340901, NP_001340902, NP_001340903, NP_001340904, NP_001340905, NP_001425829, NP_001425830, NP_001425831, NP_001425832, 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 (53 total): helix 13, strand 12, 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 by resolution:

PDB	Title	Method	Resolution (Å)
3RZV	The Crystal Structure of a E280A Mutant of the Catalytic Domain of AMSH	X-RAY DIFFRACTION	1.67
2XZE	Structural basis for AMSH-ESCRT-III CHMP3 interaction	X-RAY DIFFRACTION	1.75
3RZU	The Crystal Structure of the Catalytic Domain of AMSH	X-RAY DIFFRACTION	2.5
9LE4	Crystal structure of the MIT-CD complex of STAMBP	X-RAY DIFFRACTION	2.6
5IXF	Solution structure of the STAM2 SH3 with AMSH derived peptide complex	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, Peptidases, Metallopeptidases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; plasma membrane

Antibody reliability (HPA): IH uncertain · IF supported

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)

Position	Role
280	indirect zinc-binding

Ligand- & substrate-binding residues (7)

Position	Role
396	Zn(2+)
398	Zn(2+)
335	Zn(2+)
337	Zn(2+)
348	Zn(2+)
350	Zn(2+)
390	Zn(2+)

Post-translational modifications (5)

Type	Positions
Phosphoserine	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 ubiquitinated stam …

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-5689901	Metalloprotease DUBs	curated
R-HSA-5688426	Deubiquitination	—
R-HSA-392499	Metabolism of proteins	—
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 (8): 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)

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

3 top-level categories:

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

GO top-level categories

40 GO namespaces:

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
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
cell division site	1
plasma membrane region	1
extracellular vesicle	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
mitotic cytokinesis	BP	mutant phenotype
negative regulation of Ras protein signal transduction	BP	mutant phenotype
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	mutant phenotype
protein deubiquitination	BP	mutant phenotype
cleavage furrow	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
nucleoplasm	CC	direct assay
plasma membrane	CC	direct assay
K63-linked deubiquitinase activity	MF	direct assay
deubiquitinase activity	MF	direct assay
protein domain specific binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,718 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAMBP	CHMP3	Q9Y3E7	847
STAMBP	A0A140T963	A0A140T963	847
STAMBP	STAM2	O75886	842
STAMBP	RNF11	Q9Y3C5	812
STAMBP	CHMP1B	Q7LBR1	807
STAMBP	COPS5	Q92905	804
STAMBP	SMURF2	Q9HAU4	780
STAMBP	USP8	P40818	776
STAMBP	VPS4A	Q9UN37	759
STAMBP	KNSTRN	Q9Y448	716
STAMBP	ZUP1	Q96AP4	715
STAMBP	CHMP2A	O43633	701
STAMBP	CHMP6	Q96FZ7	678
STAMBP	STAM	Q92783	650
STAMBP	PSMD14	O00487	649

IntAct

Human interaction partners of STAMBP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 44 partners by confidence:

Partner	Interaction type	MIscore	Records
CHMP3	physical association	0.960	30
CHMP1B	physical association	0.960	21
GRB2	physical association	0.930	6
STAM2	physical association	0.840	9
CHMP1A	physical association	0.830	7
GRAP2	physical association	0.810	6
STAM	physical association	0.770	7
PIK3C2A	association	0.730	4
RNF11	physical association	0.700	5
UBB	physical association	0.680	4
BMP2K	physical association	0.660	1
CHMP2A	physical association	0.660	1
TRIP13	physical association	0.620	4
CHMP5	physical association	0.570	2
ATXN1	physical association	0.560	6
APOBEC3A	physical association	0.560	3
CCT5	physical association	0.560	3
JPH3	physical association	0.560	3
PRKN	physical association	0.560	3
TARDBP	physical association	0.560	3
CDKL3	association	0.560	2
CHMP4B	physical association	0.550	3
CHMP4A	physical association	0.550	2
CIMAP1C	association	0.530	2
SMAD6	physical association	0.510	2
UBC	deubiquitination reaction	0.440	1
CHMP4C	physical association	0.400	1
ALAS1	physical association	0.370	1
AMN	physical association	0.370	1
CTNNBL1	physical association	0.370	1

BioGRID (260 interactions; top human partners by supporting records): CHMP3 (Two-hybrid; 23 records), STAM (Reconstituted Complex; 19 records), UBC (Biochemical Activity; 15 records), GRB2 (Two-hybrid; 12 records), CHMP1B (Two-hybrid; 11 records), CHMP1A (Affinity Capture-MS; 10 records), GRAP2 (Affinity Capture-MS; 8 records), CLTC (Affinity Capture-MS; 6 records), STAM2 (Two-hybrid; 6 records), CHMP2A (Affinity Capture-MS; 5 records), PIK3C2A (Affinity Capture-MS; 4 records), ULK1 (Affinity Capture-Western; 4 records), CDKL3 (Affinity Capture-MS; 3 records), CHMP4B (Two-hybrid; 3 records), CLINT1 (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 3 of 7 signaling 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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
RNF11-SMURF2-STAMBP complex	3	RNF11, SMURF2, STAMBP

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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
InlB-mediated entry of Listeria monocytogenes into host cell	5	131.3×	2e-08
Endosomal Sorting Complex Required For Transport (ESCRT)	10	127.0×	4e-17
Budding and maturation of HIV virion	8	112.5×	4e-13
Negative regulation of MET activity	5	89.5×	1e-07
Late endosomal microautophagy	7	78.8×	3e-10
Pyroptosis	5	72.9×	3e-07
EGFR downregulation	5	59.7×	7e-07
Sealing of the nuclear envelope (NE) by ESCRT-III	5	59.7×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	8	198.3×	8e-16
late endosome to lysosome transport	8	198.3×	8e-16
viral budding via host ESCRT complex	8	160.5×	5e-15
multivesicular body sorting pathway	8	160.5×	5e-15
midbody abscission	8	146.5×	1e-14
regulation of mitotic spindle assembly	8	146.5×	1e-14
multivesicular body assembly	10	131.7×	2e-17
regulation of centrosome duplication	7	128.2×	2e-12

Disease & clinical

Genetic variants

Variant evidence for STAMBP: 225 ClinVar records (20 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	7
Uncertain significance	85
Likely benign	69
Benign	19

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 20 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
212320	NM_213622.4(STAMBP):c.1119-6T>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
424125	NM_213622.4(STAMBP):c.230A>G (p.His77Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
817554	NM_213622.4(STAMBP):c.232C>T (p.Arg78Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
50796	NM_213622.4(STAMBP):c.299T>A (p.Phe100Tyr)	Pathogenic	criteria provided, single submitter	2
420170	NM_213622.4(STAMBP):c.938C>T (p.Thr313Ile)	Pathogenic	criteria provided, single submitter	1
436881	NM_213622.4(STAMBP):c.649C>T (p.Gln217Ter)	Pathogenic	criteria provided, single submitter	1
503843	NM_213622.4(STAMBP):c.503_524del (p.Met168fs)	Pathogenic	criteria provided, single submitter	1
1034283	NM_213622.4(STAMBP):c.843_844del (p.Cys282fs)	Pathogenic	criteria provided, single submitter	1
1366374	NM_213622.4(STAMBP):c.1214del (p.Phe405fs)	Pathogenic	criteria provided, single submitter	1
2028025	NM_213622.4(STAMBP):c.487dup (p.His163fs)	Pathogenic	criteria provided, single submitter	1
2637512	NM_213622.4(STAMBP):c.5_6dup (p.Asp3fs)	Pathogenic	criteria provided, single submitter	1
424114	NM_213622.4(STAMBP):c.932G>T (p.Cys311Phe)	Likely pathogenic	criteria provided, single submitter	1
1992771	NM_213622.4(STAMBP):c.868-1G>A	Likely pathogenic	criteria provided, single submitter	1
2690758	NM_213622.4(STAMBP):c.1006-2A>T	Likely pathogenic	criteria provided, single submitter	1
3767307	NM_213622.4(STAMBP):c.376-1G>A	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore STAMBP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 1,292):

Position(s)	Effect	Δscore	Sites
2:73830837	acceptor_gain	1.0000
2:73830843–73830844	acceptor_loss	1.0000	6
2:73831014	donor_gain	1.0000
2:73844811–73844812	acceptor_loss	1.0000	5
2:73845152	acceptor_gain	1.0000
2:73845157	acceptor_gain	1.0000
2:73845165–73845166	acceptor_loss	1.0000	6
2:73845263	donor_loss	1.0000	2
2:73847385–73847386	acceptor_loss	1.0000	6
2:73847570	donor_gain	1.0000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.87e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000343
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000803

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
microcephaly-capillary malformation syndrome	Definitive	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (11 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

11 panels:

Panel	Rating
Clefting	green
DDG2P	green
Early onset or syndromic epilepsy	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Severe microcephaly	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Vascular skin disorders	green

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 phenotypes (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
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0009879	Simplified gyral pattern
HP:0009882	Short distal phalanx of finger
HP:0010721	Abnormal hair whorl
HP:0011344	Severe global developmental delay
HP:0012448	Delayed myelination
HP:0012469	Infantile spasms
HP:0012510	Extra-axial cerebrospinal fluid accumulation
HP:0025104	Capillary malformation
HP:0025517	Hypoplastic hippocampus
HP:0030084	Clinodactyly

GWAS associations

9 associations:

Study	Trait	p-value
GCST006249_44	Serum metabolite levels	8e-29
GCST006879_7	Blood metabolite levels	2e-15
GCST006879_9	Blood metabolite levels	2e-14
GCST012020_550	Serum metabolite levels	3e-14
GCST006879_6	Blood metabolite levels	5e-14
GCST006879_11	Blood metabolite levels	1e-12
GCST005025_21	Anti-saccade response	1e-6
GCST005025_7	Anti-saccade response	3e-6
GCST011354_11	Bell’s palsy	5e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0006874	antisaccade response measurement

MeSH disease descriptors

1 disease descriptors:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

22 measured of 29 human assays (29 total across all organisms); most potent 22 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4104719	IC50	200 nM
CHEMBL4100384	IC50	300 nM
CHEMBL4586347	IC50	330 nM
Capzimin	IC50	340 nM	US-10005735: Inhibitors of RPN11
CHEMBL4073553	IC50	390 nM
CHEMBL4069023	IC50	800 nM
CHEMBL4088568	IC50	800 nM
CHEMBL4060337	IC50	900 nM
CHEMBL4091693	IC50	1000 nM
CHEMBL4078891	IC50	1000 nM
CHEMBL4095913	IC50	1000 nM
CHEMBL4095417	IC50	1100 nM
CHEMBL4099434	IC50	1200 nM
CHEMBL4070821	IC50	1200 nM
CHEMBL4103171	IC50	1600 nM
CHEMBL4065318	IC50	2600 nM
CHEMBL4093962	IC50	2900 nM
CHEMBL4083926	IC50	3200 nM
CHEMBL4062208	IC50	4000 nM
CHEMBL4105598	IC50	5000 nM
CHEMBL4059915	IC50	6400 nM
CHEMBL4085174	IC50	82000 nM

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	affects cotreatment, increases oxidation	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

4 cell lines: 3 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_F5IC	EDITGENE STAMBP Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_TQ54	HAP1 STAMBP (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for STAMBP across ~30M SureChEMBL compounds — explore on Sugi Predict.