STAP1

Summary

STAP1 (signal transducing adaptor family member 1, HGNC:24133) is a protein-coding gene on chromosome 4q13.2, encoding Signal-transducing adaptor protein 1 (Q9ULZ2). In BCR signaling, appears to function as a docking protein acting downstream of TEC and participates in a positive feedback loop by increasing the activity of TEC.

The protein encoded by this gene contains a proline-rich region, a pleckstrin homology (PH) domain, and a region in the carboxy terminal half with similarity to the Src Homology 2 (SH2) domain. This protein is a substrate of tyrosine-protein kinase Tec, and its interaction with tyrosine-protein kinase Tec is phosphorylation-dependent. This protein is thought to participate in a positive feedback loop by upregulating the activity of tyrosine-protein kinase Tec. Variants of this gene have been associated with autosomal-dominant hypercholesterolemia (ADH), which is characterized by elevated low-density lipoprotein cholesterol levels and in increased risk of coronary vascular disease. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 26228 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 160 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 21 tissues, sQTL in 5 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.98 (unconstrained)
• MANE Select transcript: NM_012108
• Notable: 160 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24133
Approved symbol	STAP1
Name	signal transducing adaptor family member 1
Location	4q13.2
Locus type	gene with protein product
Status	Approved
Aliases	STAP-1, BRDG1
Ensembl gene	ENSG00000035720
Ensembl biotype	protein_coding
OMIM	604298
Entrez	26228

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

MANE Select: ENST00000265404

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

ENST00000265404, ENST00000396225, ENST00000894638, ENST00000894639, ENST00001117789, ENST00001129378, ENST00001133513

RefSeq mRNA: 2 — MANE Select: NM_012108 NM_001317769, NM_012108

CCDS: CCDS3515

Canonical transcript exons

ENST00000265404 — 9 exons

Exon	Start	End
ENSE00000371763	67571084	67571155
ENSE00000718793	67575385	67575498
ENSE00000718799	67577203	67577259
ENSE00000718804	67581305	67581471
ENSE00000718819	67583574	67583702
ENSE00000718848	67590884	67590953
ENSE00000718890	67593260	67593356
ENSE00001072365	67606296	67607337
ENSE00003847227	67558727	67558929

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 87.79.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5981 / max 267.2855, expressed in 256 samples.

Highest expression (Bgee): lymph node, epithelium of nasopharynx, spleen, metanephros cortex, vermiform appendix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

STAP1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Hippocampus	eqtl	7.0e-21	-0.78	4:67576912:A:T
Spleen	sqtl	1.4e-19	+0.88	4:67568744:C:T
Cells EBV-transformed lymphocytes	sqtl	5.9e-18	+0.84	4:67576912:A:T
Adipose Subcutaneous	eqtl	2.3e-17	-0.53	4:67553767:C:T
Testis	sqtl	2.2e-14	-0.73	4:67576912:A:T
Testis	eqtl	8.7e-12	-0.32	4:67577590:T:G
Nerve Tibial	eqtl	1.7e-11	-0.47	4:67553767:C:T
Artery Aorta	eqtl	7.7e-10	-0.46	4:67549661:G:A
Artery Tibial	eqtl	6.4e-08	-0.34	4:67553767:C:T
Brain Cerebellar Hemisphere	eqtl	6.0e-07	+0.56	4:67626342:A:G
Lung	eqtl	1.4e-06	-0.32	4:67564405:C:T
Brain Cerebellum	eqtl	2.1e-05	+0.52	4:67609129:G:C
Artery Coronary	eqtl	1.7e-04	-0.33	4:67549661:G:A
Whole Blood	eqtl	8.0e-04	-0.10	4:67457912:A:G
Spleen	eqtl	3.6e-03	+0.11	4:67593219:G:C
Breast Mammary Tissue	eqtl	3.6e-03	-0.31	4:67553767:C:T
Skin Sun Exposed Lower leg	eqtl	5.7e-03	-0.25	4:67403763:G:C
Heart Atrial Appendage	eqtl	1.5e-02	+0.24	4:67626055:T:A
Colon Sigmoid	eqtl	2.0e-02	+0.20	4:67620749:A:G
Bladder	eqtl	2.9e-02	+1.14	4:67801930:T:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
47810	1.9033	216
47812	1.5864	181
47811	0.1084	55

Top tissues by expression

showing 100 of 264 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	87.79	gold quality
epithelium of nasopharynx	UBERON:0001951	85.00	gold quality
spleen	UBERON:0002106	84.62	gold quality
metanephros cortex	UBERON:0010533	84.55	gold quality
vermiform appendix	UBERON:0001154	84.20	gold quality
granulocyte	CL:0000094	80.86	gold quality
caecum	UBERON:0001153	78.46	gold quality
bone marrow cell	CL:0002092	78.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.60	gold quality
bone marrow	UBERON:0002371	77.45	gold quality
tonsil	UBERON:0002372	76.28	gold quality
superficial temporal artery	UBERON:0001614	75.55	gold quality
blood	UBERON:0000178	74.21	gold quality
adult mammalian kidney	UBERON:0000082	72.91	gold quality
colonic epithelium	UBERON:0000397	70.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	69.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.65	gold quality
renal medulla	UBERON:0000362	69.57	gold quality
kidney	UBERON:0002113	69.02	gold quality
rectum	UBERON:0001052	68.54	gold quality
leukocyte	CL:0000738	67.03	gold quality
small intestine	UBERON:0002108	66.81	gold quality
cortex of kidney	UBERON:0001225	66.57	gold quality
nephron tubule	UBERON:0001231	66.17	silver quality
seminal vesicle	UBERON:0000998	65.78	gold quality
mononuclear cell	CL:0000842	65.59	gold quality
mucosa of transverse colon	UBERON:0004991	65.42	gold quality
monocyte	CL:0000576	65.20	gold quality
gall bladder	UBERON:0002110	65.07	gold quality
metanephros	UBERON:0000081	64.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	63.23	gold quality
trabecular bone tissue	UBERON:0002483	62.99	silver quality
nasal cavity mucosa	UBERON:0001826	61.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	61.25	silver quality
kidney epithelium	UBERON:0004819	60.62	silver quality
ileal mucosa	UBERON:0000331	60.43	gold quality
thymus	UBERON:0002370	59.89	silver quality
colonic mucosa	UBERON:0000317	59.68	gold quality
duodenum	UBERON:0002114	59.35	gold quality
sperm	CL:0000019	59.20	silver quality
bronchial epithelial cell	CL:0002328	59.11	silver quality
male germ cell	CL:0000015	58.67	silver quality
epithelium of bronchus	UBERON:0002031	58.04	silver quality
transverse colon	UBERON:0001157	57.83	gold quality
intestine	UBERON:0000160	57.72	gold quality
bronchus	UBERON:0002185	57.72	silver quality
amniotic fluid	UBERON:0000173	57.03	silver quality
smooth muscle tissue	UBERON:0001135	56.89	gold quality
decidua	UBERON:0002450	56.55	gold quality
metanephric glomerulus	UBERON:0004736	56.35	silver quality
upper lobe of left lung	UBERON:0008952	55.86	gold quality
upper lobe of lung	UBERON:0008948	55.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.20	gold quality
large intestine	UBERON:0000059	55.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	54.69	gold quality
jejunal mucosa	UBERON:0000399	54.63	gold quality
colon	UBERON:0001155	54.50	gold quality
lung	UBERON:0002048	53.94	gold quality
body of stomach	UBERON:0001161	53.74	gold quality
gingival epithelium	UBERON:0001949	53.59	gold quality
superior surface of tongue	UBERON:0007371	53.56	gold quality
mucosa of stomach	UBERON:0001199	53.37	gold quality
right lung	UBERON:0002167	53.18	gold quality
stomach	UBERON:0000945	52.94	gold quality
nasal cavity epithelium	UBERON:0005384	52.82	gold quality
lower esophagus mucosa	UBERON:0035834	52.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	52.61	gold quality
lower esophagus	UBERON:0013473	52.55	gold quality
urinary bladder	UBERON:0001255	52.44	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
esophagus	UBERON:0001043	52.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	51.89	gold quality
cerebellar vermis	UBERON:0004720	51.80	gold quality
corpus epididymis	UBERON:0004359	51.77	gold quality
minor salivary gland	UBERON:0001830	51.76	gold quality
buccal mucosa cell	CL:0002336	51.66	silver quality
esophagus mucosa	UBERON:0002469	51.48	gold quality
endothelial cell	CL:0000115	51.32	gold quality
jejunum	UBERON:0002115	51.20	gold quality
mouth mucosa	UBERON:0003729	50.97	gold quality
oocyte	CL:0000023	50.90	gold quality
testis	UBERON:0000473	50.85	gold quality
oral cavity	UBERON:0000167	50.81	gold quality
saliva-secreting gland	UBERON:0001044	50.79	gold quality
endometrium	UBERON:0001295	50.47	gold quality
pylorus	UBERON:0001166	50.30	silver quality
prostate gland	UBERON:0002367	50.12	gold quality
left testis	UBERON:0004533	50.07	gold quality
right coronary artery	UBERON:0001625	49.61	gold quality
gingiva	UBERON:0001828	49.60	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.60	gold quality
omental fat pad	UBERON:0010414	49.60	gold quality
peritoneum	UBERON:0002358	49.57	gold quality
fundus of stomach	UBERON:0001160	49.40	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
adipose tissue of abdominal region	UBERON:0007808	49.24	gold quality
skin of hip	UBERON:0001554	49.21	silver quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
quadriceps femoris	UBERON:0001377	49.11	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	406.06
E-ANND-3	yes	24.69
E-CURD-114	yes	11.39
E-CURD-112	yes	10.09

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 146 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	199.8	high
Ovary	tissue	164.8	medium
Thymus	tissue	155.3
Pancreas	tissue	142.6	medium
Lymph node	tissue	138.9	high
Tonsil	tissue	133.8	high
Breast	tissue	118.8	high
Epididymis	tissue	116.4	low
Vagina	tissue	109.1	high
Adrenal gland	tissue	108.4	high
Salivary gland	tissue	106.8	medium
Liver	tissue	105.9	medium
Pituitary gland	tissue	103.9
Colon	tissue	100.9	high
Heart muscle	tissue	98.2	medium
Fallopian tube	tissue	97.0	medium
Rectum	tissue	93.4	high
Urinary bladder	tissue	89.8	high
Tongue	tissue	88.7
Parathyroid gland	tissue	84.8
Skeletal muscle	tissue	83.4	medium
Kidney	tissue	83.2	medium
Stomach 1	tissue	81.0	low
Spleen	tissue	79.9	high
Small intestine	tissue	79.4	high
Cervix	tissue	77.9	high
Thyroid gland	tissue	77.0	medium
Appendix	tissue	74.2	high
Duodenum	tissue	72.4	high
Esophagus	tissue	70.2	high
Skin 1	tissue	67.3	high
Smooth muscle	tissue	63.6	medium
Gallbladder	tissue	62.6	medium
Prostate	tissue	62.2	medium
Endometrium 1	tissue	62.1	low
Seminal vesicle	tissue	61.9	medium
Placenta	tissue	61.2	high
Lung	tissue	57.0	high
Adipose tissue	tissue	55.3	low
Tonsil	tissue	47.7	high
Choroid plexus	tissue	44.2
Retina	tissue	39.7
Lymph node	tissue	38.1	high
Nucleus accumbens	tissue	32.8
Locus coeruleus	tissue	32.2
Testis	tissue	31.4	medium
Hippocampus	tissue	28.0	low
Postcentral gyrus	tissue	25.0
Spleen	tissue	14.7	medium
Appendix	tissue	14.6	high
Spinal cord	tissue	14.1
Pons	tissue	13.6
Thalamus	tissue	13.2
Substantia nigra	tissue	12.9
Corpus callosum	tissue	12.7
Superior colliculi	tissue	12.5
Midbrain	tissue	12.0
Medulla oblongata	tissue	11.8
Cerebral cortex	tissue	11.6	medium
Basal ganglia	tissue	11.6	low

Brain sub-regions (HPA Brain Atlas): detected in 324; highest nTPM — Blood vessel (123.3), Lateral funiculus (white matter) (53.9), Cerebellar white matter (49.8), Dorsal funiculus (white matter) (48.9), Anterior funiculus (white matter) (48.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting STAP1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 67 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863

Functional genomics

gnomAD constraint: pLI 0.00112, LOEUF 0.982, missense Z 0.0159 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000265404 — one region, missense o/e 1.02.

Literature-anchored findings (GeneRIF, showing 9)

• Mutations in STAP1 are associated with autosomal dominant hypercholesterolemia. (PMID:25035151)
• STAP1 associated with Familial Hypercholesterolemia and Polygenic Hypercholesterolemia in patients with Acute Coronary Syndrome , age </=65 years, and LDL-C levels >/=160 mg/dl. (PMID:28958330)
• The findings confirm and extend the linkage between STAP1 variants and FH, and point to an important role of this adaptor protein within a signaling pathway that affects cholesterol homeostasis. (PMID:30308187)
• Predicted pathogenic mutations in STAP1 are not associated with clinically defined familial hypercholesterolemia. (PMID:31809983)
• Our combined studies in mouse models and carriers of STAP1 variants indicate that STAP1 is not a familial hypercholesterolemia gene. (PMID:31996024)
• Positive interactions between STAP-1 and BCR-ABL influence chronic myeloid leukemia cell proliferation and survival. (PMID:33845308)
• Signal-transducing adaptor protein-1 and protein-2 in hematopoiesis and diseases. (PMID:34780812)
• Diagnostic and prognostic value of STAP1 and AHNAK methylation in peripheral blood immune cells for HBV-related hepatopathy. (PMID:36713363)
• Relationship between STAP1 methylation in peripheral blood T cells and the clinicopathological characteristics and prognosis of patients within 5-cm diameter HCC. (PMID:37526444)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Stap1	ENSMUSG00000029254
rattus_norvegicus	Stap1	ENSRNOG00000002014

Paralogs (1): STAP2 (ENSG00000178078)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1926193) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
male infertility	1

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
UBA6-DT	ncRNA	550112
UBA6	protein-coding	55236
CENPC	protein-coding	1060
GNRHR	protein-coding	2798

Protein

Protein identifiers

Signal-transducing adaptor protein 1 — Q9ULZ2 (reviewed: Q9ULZ2)

Alternative names: BCR downstream-signaling protein 1, Docking protein BRDG1, Stem cell adaptor protein 1

All UniProt accessions (1): Q9ULZ2

UniProt curated annotations — full annotation on UniProt →

Function. In BCR signaling, appears to function as a docking protein acting downstream of TEC and participates in a positive feedback loop by increasing the activity of TEC.

Subunit / interactions. Interacts with KIT and CSF1R. Interacts with URI1; the interaction is phosphorylation-dependent and occurs in a growth-dependent manner.

Subcellular location. Nucleus. Cytoplasm. Mitochondrion.

Post-translational modifications. Phosphorylated on tyrosine by TEC. Phosphorylated on tyrosine by KIT.

RefSeq proteins (2): NP_001304698, NP_036240* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035877	STAP1_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR039111	STAP1/STAP2	Family

Pfam: PF00017, PF00169

UniProt features (26 total): strand 15, helix 5, domain 2, chain 1, turn 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
3MAZ	Crystal Structure of the Human BRDG1/STAP-1 SH2 Domain in Complex with the NTAL pTyr136 …	X-RAY DIFFRACTION	1.9
1X1F	Solution structure of the PH domain of human Docking protein BRDG1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULZ2-F1	79.06	0.39

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nuclear bodies

Antibody reliability (HPA): IH enhanced · 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.

Post-translational modifications (1)

Type	Positions
Phosphotyrosine	168

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 369 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, WALLACE_PROSTATE_CANCER_RACE_UP, HNF3ALPHA_Q6, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (11): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), positive regulation of gene expression (GO:0010628), negative regulation of macrophage chemotaxis (GO:0010760), positive regulation of B cell receptor signaling pathway (GO:0050861), positive regulation of phagocytosis, engulfment (GO:0060100), cellular response to lipopolysaccharide (GO:0071222), negative regulation of ruffle assembly (GO:1900028), negative regulation of macrophage colony-stimulating factor signaling pathway (GO:1902227), positive regulation of microglial cell activation (GO:1903980), negative regulation of microglial cell migration (GO:1904140), positive regulation of microglial cell mediated cytotoxicity (GO:1904151)

GO Molecular Function (10): phosphotyrosine residue binding (GO:0001784), transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068), macrophage colony-stimulating factor receptor binding (GO:0005157), phospholipid binding (GO:0005543), protein kinase binding (GO:0019901), protein tyrosine kinase activator activity (GO:0030296), signaling adaptor activity (GO:0035591), protein binding (GO:0005515), protein-macromolecule adaptor activity (GO:0030674), receptor tyrosine kinase binding (GO:0030971)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), nuclear body (GO:0016604), protein-containing complex (GO:0032991)

GO top-level categories

58 GO namespaces:

Category	Terms
negative regulation of macrophage migration	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
enzyme-linked receptor protein signaling pathway	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
B cell receptor signaling pathway	1
regulation of B cell receptor signaling pathway	1
positive regulation of antigen receptor-mediated signaling pathway	1
phagocytosis, engulfment	1
positive regulation of phagocytosis	1
regulation of phagocytosis, engulfment	1
positive regulation of membrane invagination	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
ruffle assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of ruffle assembly	1
negative regulation of cytokine-mediated signaling pathway	1
macrophage colony-stimulating factor signaling pathway	1
regulation of macrophage colony-stimulating factor signaling pathway	1
microglial cell activation	1
positive regulation of macrophage activation	1
positive regulation of neuroinflammatory response	1
regulation of microglial cell activation	1
negative regulation of glial cell migration	1
microglial cell migration	1
regulation of microglial cell migration	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of myeloid leukocyte mediated immunity	1
microglial cell mediated cytotoxicity	1
regulation of microglial cell mediated cytotoxicity	1
protein phosphorylated amino acid binding	1
cell surface receptor protein tyrosine kinase signaling pathway	1
signaling receptor complex adaptor activity	1
receptor tyrosine kinase binding	1
cytokine receptor binding	1
lipid binding	1
kinase binding	1
protein tyrosine kinase activity	1
protein kinase activator activity	1
protein-macromolecule adaptor activity	1
binding	1
protein binding	1
molecular adaptor activity	1
signaling receptor binding	1
protein tyrosine kinase binding	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
cellular_component	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of B cell receptor signaling pathway	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
mitochondrion	CC	direct assay
nuclear body	CC	direct assay
nucleus	CC	direct assay
protein-containing complex	CC	direct assay
phosphotyrosine residue binding	MF	physical interaction
protein kinase binding	MF	physical interaction
protein tyrosine kinase activator activity	MF	direct assay
signaling adaptor activity	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 474 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAP1	BMX	P51813	741
STAP1	ITK	Q08881	628
STAP1	LDLRAP1	Q5SW96	614
STAP1	TXK	P42681	575
STAP1	BTK	Q06187	540
STAP1	BCR	P11274	504
STAP1	ABCG5	Q9H222	499
STAP1	PCSK9	Q8NBP7	498
STAP1	LIPA	P38571	491
STAP1	IRS2	Q9Y4H2	487
STAP1	PLEK2	Q9NYT0	480
STAP1	APOB	P04114	469
STAP1	PLEK	P08567	457
STAP1	ABCG8	Q9H221	452
STAP1	IRS1	P35568	436

IntAct

Human interaction partners of STAP1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
SH3KBP1	physical association	0.750	4
RETREG3	physical association	0.720	8
GRIPAP1	physical association	0.560	3
SULT1A1	association	0.530	2
GAB1	direct interaction	0.440	3
KIT	direct interaction	0.440	3
MET	direct interaction	0.440	3
AR	direct interaction	0.440	2
ALK	physical association	0.370	1
CAPZA2	association	0.350	1

BioGRID (31 interactions; top human partners by supporting records): SH3KBP1 (Two-hybrid; 5 records), CD2AP (Affinity Capture-MS; 3 records), SULT1A1 (Affinity Capture-MS; 3 records), CAPZA2 (Affinity Capture-MS; 2 records), CCND3 (Affinity Capture-MS; 2 records), FAM134C (Two-hybrid; 2 records), AR (Reconstituted Complex), ATG16L1 (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), EGFR (Reconstituted Complex), ERBB2 (Reconstituted Complex), ERBB3 (Reconstituted Complex), ERBB4 (Reconstituted Complex), GAB1 (Reconstituted Complex)

SIGNOR signaling

6 signaling interactions:

A	Effect	B	Mechanism
TEC	“up-regulates activity”	STAP1	phosphorylation
PTK2B	“up-regulates activity”	STAP1	phosphorylation
STAP1	“up-regulates activity”	TEC	binding
KIT	“up-regulates activity”	STAP1	phosphorylation
STAP1	“up-regulates activity”	STAT5A	binding
STAP1	“up-regulates activity”	KIT	binding

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
URI complex (Unconventional prefoldin RPB5 Interactor)	9	RUVBL1, SKP1, SKP2, STAP1, CUL1, PFDN2, POLR2E, RUVBL2, URI1

Disease & clinical

Genetic variants

Variant evidence for STAP1: 160 ClinVar records (1 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	80
Likely benign	52
Benign	14

Top pathogenic / likely-pathogenic (1)

Showing all 1 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
189309	NM_012108.4(STAP1):c.139A>G (p.Thr47Ala)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore STAP1’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.

AlphaMissense

541 missense substitutions predicted likely pathogenic (of 1,940 scored), across 144 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H226	8	0.942	0.989
F256	8	0.918	0.988
W112	7	0.986	0.999
R203	7	0.979	0.997
W46	7	0.962	0.986
E145	7	0.951	0.974
R18	7	0.950	0.996
F115	7	0.926	0.991
F55	7	0.923	0.981
C178	7	0.905	0.989
E48	7	0.902	0.974
F179	7	0.897	0.984
F267	7	0.892	0.960
N199	7	0.853	0.985
R50	6	0.970	0.994
G133	6	0.927	0.970
R12	6	0.921	0.985
L191	6	0.897	0.993
P132	6	0.881	0.938
K228	6	0.872	0.965

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Kidney Chromophobe)

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	5.84e-05
Lung Adenocarcinoma (TCGA)	favorable	8.76e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000193
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	0.000428

Disease associations

OMIM: gene MIM:604298 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): hypercholesterolemia, familial, 1 (MONDO:0007750)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

GWAS associations

1 associations:

Study	Trait	p-value
GCST000005_2	Parkinson’s disease	2e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
GSK-J4	decreases expression	1
bisphenol F	decreases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Estradiol	decreases expression, affects cotreatment	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methapyrilene	decreases methylation	1
Methotrexate	increases expression	1
Nickel	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

28 trials:

NCT	Phase	Status	Title
NCT06231459	Phase 4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	Phase 3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	Phase 3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	Phase 3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	Phase 3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	Phase 3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	Phase 3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	Phase 3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	Phase 2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	Phase 2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	Phase 2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	Phase 1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	Phase 1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	UNKNOWN	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab