SKAP1

Summary

SKAP1 (src kinase associated phosphoprotein 1, HGNC:15605) is a protein-coding gene on chromosome 17q21.32, encoding Src kinase-associated phosphoprotein 1 (Q86WV1). Positively regulates T-cell receptor signaling by enhancing the MAP kinase pathway.

This gene encodes a T cell adaptor protein, a class of intracellular molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity. The encoded protein contains a unique N-terminal region followed by a PH domain and C-terminal SH3 domain. Along with the adhesion and degranulation-promoting adaptor protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins.

Source: NCBI Gene 8631 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_003726

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15605
Approved symbol	SKAP1
Name	src kinase associated phosphoprotein 1
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	SKAP55
Ensembl gene	ENSG00000141293
Ensembl biotype	protein_coding
OMIM	604969
Entrez	8631

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000336915, ENST00000579336, ENST00000579476, ENST00000581400, ENST00000581419, ENST00000583844, ENST00000584709, ENST00000584924, ENST00000852281, ENST00000852282, ENST00000852283, ENST00000852284, ENST00000970118

RefSeq mRNA: 2 — MANE Select: NM_003726 NM_001075099, NM_003726

CCDS: CCDS32674

Canonical transcript exons

ENST00000336915 — 13 exons

Exon	Start	End
ENSE00001290851	48133442	48133816
ENSE00001342503	48345905	48346006
ENSE00001342511	48363789	48363814
ENSE00001342515	48396680	48396785
ENSE00002733332	48430075	48430214
ENSE00003479148	48182394	48182457
ENSE00003530462	48170609	48170659
ENSE00003532350	48162469	48162569
ENSE00003542041	48189423	48189500
ENSE00003545120	48137229	48137337
ENSE00003557988	48184723	48184847
ENSE00003583015	48180054	48180248
ENSE00003619639	48187843	48187926

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 96.24.

FANTOM5 (CAGE): breadth broad, TPM avg 6.6320 / max 276.7148, expressed in 281 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166653	4.5402	243
166652	1.9011	169
166655	0.0550	32
166654	0.0442	23
166637	0.0384	6
166651	0.0152	5
166636	0.0136	5
166639	0.0075	3
166640	0.0062	1
166638	0.0058	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.24	gold quality
right lobe of liver	UBERON:0001114	91.60	gold quality
right uterine tube	UBERON:0001302	90.85	gold quality
lymph node	UBERON:0000029	88.76	gold quality
blood	UBERON:0000178	88.21	gold quality
pituitary gland	UBERON:0000007	86.13	gold quality
right testis	UBERON:0004534	85.79	gold quality
liver	UBERON:0002107	85.74	gold quality
left testis	UBERON:0004533	85.46	gold quality
adenohypophysis	UBERON:0002196	85.22	gold quality
right adrenal gland cortex	UBERON:0035827	84.61	gold quality
metanephros cortex	UBERON:0010533	83.31	gold quality
spleen	UBERON:0002106	83.27	gold quality
testis	UBERON:0000473	82.69	gold quality
adult mammalian kidney	UBERON:0000082	82.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.33	gold quality
right adrenal gland	UBERON:0001233	81.74	gold quality
bone marrow cell	CL:0002092	81.48	gold quality
vermiform appendix	UBERON:0001154	80.70	gold quality
left adrenal gland cortex	UBERON:0035825	80.22	gold quality
adrenal cortex	UBERON:0001235	79.72	gold quality
colonic epithelium	UBERON:0000397	79.67	gold quality
left adrenal gland	UBERON:0001234	79.64	gold quality
tonsil	UBERON:0002372	79.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.28	gold quality
thymus	UBERON:0002370	78.96	gold quality
adrenal gland	UBERON:0002369	78.46	gold quality
sperm	CL:0000019	78.33	gold quality
mucosa of transverse colon	UBERON:0004991	77.23	gold quality
caecum	UBERON:0001153	76.81	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2144.68
E-GEOD-180759	yes	1369.34
E-HCAD-30	yes	718.47
E-MTAB-11268	yes	626.60
E-CURD-119	yes	45.90
E-CURD-122	yes	38.76
E-MTAB-10287	yes	30.65
E-ANND-3	yes	12.05
E-CURD-112	yes	4.37
E-CURD-120	no	43.66

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IL2	Activation

miRNA regulators (miRDB)

31 targeting SKAP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-668-3P	96.18	65.80	673
HSA-MIR-4471	95.11	66.84	755

Literature-anchored findings (GeneRIF, showing 17)

• SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription. (PMID:11909961)
• observation that adapter protein SKAP55 formed homodimers through its SH3 domain and SK region (PMID:12171928)
• SKAP-55 regulates integrin-mediated adhesion and conjugate formation between T cells and antigen-presenting cells (PMID:12652296)
• stimuli that signal for the stabilization of SKAP55 may play an important role in T cell adhesion and conjugate formation (PMID:15849195)
• This study reports on a RKXXY294 motif in SKAP-55 that mediates unique ADAP SH3c domain binding; it is necessary for LFA-1-mediated adhesion and cytokine production. (PMID:16461356)
• These results suggest that SKAP55 modulates signal transduction from the T cell antigen receptor to Ras by binding to RasGRP1. (PMID:17658605)
• SKAP1 protein as a novel regulator of the metaphase-to-anaphase transition and demonstrates that misregulation of the separase activation results in a reduced fidelity of chromosome segregation and a reduced genomic stability independent of the SAC. (PMID:19667759)
• findings define a T cell receptor “inside-out” pathway via N-SKAP1-C-RapL that regulates T cell adhesion, motility, and arrest times with dendritic cells in lymph nodes. (PMID:20346707)
• Single nucleotide polymorphism in SKAP1 is associated with ovarian cancer. (PMID:20852632)
• single-nucleotide polymorphisms in ARRDC3, FLT1, and SKAP1 were significant predictors for survival androgen-deprivation therapy in prostate cancer patients. (PMID:21652578)
• N-terminal myr-tagged SKAP1 for membrane binding facilitated constitutive RapL membrane and Rap1 binding and effectively substituted for PI3K and TCR ligation in the activation of LFA-1 in T cells. (PMID:21669874)
• SKAP55 dimers stabilize SLP-76 microclusters, couple SLP-76 to the force-generating systems responsible for microcluster movement, and enable adhesion via the TCR by mechanisms independent of RIAM, talin, and beta1 integrins. (PMID:24368808)
• K152 and D120 within the PH domain of SKAP55 regulate plasma membrane targeting and T cell receptor-mediated activation of LFA-1. (PMID:28052935)
• The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events. (PMID:34295339)
• THUMPD3-AS1 facilitates cell growth and aggressiveness by the miR-218-5p/SKAP1 axis in colorectal cancer. (PMID:35538197)
• Splicing annotation of endometrial cancer GWAS risk loci reveals potentially causal variants and supports a role for NF1 and SKAP1 as susceptibility genes. (PMID:36908940)
• SKAP1 Is a Novel Biomarker and Therapeutic Target for Gastric Cancer: Evidence from Expression, Functional, and Bioinformatic Analyses. (PMID:37511629)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	skap1	ENSDARG00000001498
mus_musculus	Skap1	ENSMUSG00000057058
rattus_norvegicus	Skap1	ENSRNOG00000023881

Paralogs (1): SKAP2 (ENSG00000005020)

Protein

Protein identifiers

Src kinase-associated phosphoprotein 1 — Q86WV1 (reviewed: Q86WV1)

Alternative names: Src family-associated phosphoprotein 1, Src kinase-associated phosphoprotein of 55 kDa

All UniProt accessions (6): Q86WV1, J3KS83, J3KSD4, J3QKX8, J3QRG3, J3QS38

UniProt curated annotations — full annotation on UniProt →

Function. Positively regulates T-cell receptor signaling by enhancing the MAP kinase pathway. Required for optimal conjugation between T-cells and antigen-presenting cells by promoting the clustering of integrin ITGAL on the surface of T-cells. May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells.

Subunit / interactions. Homodimer. Interacts with FYN. Interacts with PTPRC. Interacts with GRB2 when phosphorylated on Tyr-271. Interacts with FYB1, which is required for SKAP2 protein stability. Part of a complex consisting of SKAP1, FYB1 and CLNK. Interacts with RASGRP1. Interacts with FYB2.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Tissue specificity. Highly expressed in thymocytes and peripheral blood lymphocytes. Also expressed in spleen cells and testis. Present in T-cells (at protein level).

Post-translational modifications. Phosphorylated on tyrosines. Phosphorylation by FYN on Tyr-271 is required for GRB2 interaction. Phosphorylation by FYN on Tyr-295 abolishes interaction with FYB1. Tyr-232 is dephosphorylated by PTPRC.

Domain organisation. The SH3 domain interacts with FYB1.

Similarity. Belongs to the SKAP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86WV1-1	1	yes
Q86WV1-2	2

RefSeq proteins (2): NP_001068567, NP_003717* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035765	SKAP1_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR037781	SKAP_fam	Family

Pfam: PF00169, PF14604

UniProt features (33 total): strand 9, mutagenesis site 6, modified residue 5, helix 3, domain 2, sequence variant 2, region of interest 2, chain 1, splice variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1U5D	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WV1-F1	70.40	0.28

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 (5): 295, 142, 219, 232, 271

Mutagenesis-validated functional residues (6):

Position	Phenotype
219	impairs interaction with ptprc. no effect on interaction with fyn or grb2.
232	abolishes interaction with ptprc, translocation to cell membrane upon t-cell stimulation and activation of the map kinas
271	no effect on interaction with ptprc and translocation to cell membrane upon t-cell stimulation. abolishes interaction wi
295	abolishes fyb1-dependent activation of itgal clustering.
298	impairs interaction with fyb1.
333	abolishes homodimerization, interaction with fyb1 and activation of the map kinase pathway.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 264 (showing top): LI_CISPLATIN_RESISTANCE_DN, FREAC2_01, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, BENPORATH_ES_WITH_H3K27ME3, NKX25_02, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_HETEROTYPIC_CELL_CELL_ADHESION, MODULE_45, MODULE_64, AREB6_03, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, FOXO4_01, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION

GO Biological Process (13): positive regulation of cell-matrix adhesion (GO:0001954), adaptive immune response (GO:0002250), positive regulation of adaptive immune response (GO:0002821), positive regulation of integrin activation (GO:0033625), positive regulation of cell-cell adhesion mediated by integrin (GO:0033634), positive regulation of heterotypic cell-cell adhesion (GO:0034116), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), T cell receptor signaling pathway (GO:0050852), protein localization to plasma membrane (GO:0072659), positive regulation of leukocyte cell-cell adhesion (GO:1903039), immune system process (GO:0002376), positive regulation of cell adhesion (GO:0045785)

GO Molecular Function (5): SH3 domain binding (GO:0017124), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), SH2 domain binding (GO:0042169), protein binding (GO:0005515)

GO Cellular Component (10): immunological synapse (GO:0001772), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), T cell receptor complex (GO:0042101), plasma membrane raft (GO:0044853), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
positive regulation of cell-cell adhesion	3
protein domain specific binding	2
plasma membrane	2
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
immune response	1
adaptive immune response	1
regulation of adaptive immune response	1
positive regulation of immune response	1
positive regulation of protein-containing complex assembly	1
integrin activation	1
regulation of integrin activation	1
positive regulation of cell adhesion mediated by integrin	1
cell-cell adhesion mediated by integrin	1
regulation of cell-cell adhesion mediated by integrin	1
heterotypic cell-cell adhesion	1
regulation of heterotypic cell-cell adhesion	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
antigen receptor-mediated signaling pathway	1
protein localization to membrane	1
protein localization to cell periphery	1
leukocyte cell-cell adhesion	1
regulation of leukocyte cell-cell adhesion	1
biological_process	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
kinase binding	1
phosphatase binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SKAP1	FYB1	O15117	993
SKAP1	APBB1IP	Q7Z5R6	970
SKAP1	LCP2	Q13094	930
SKAP1	FYN	P06241	899
SKAP1	RASSF5	Q8WWW0	825
SKAP1	LCK	P06239	801
SKAP1	GRB2	P29354	794
SKAP1	PLCG1	P19174	740
SKAP1	SRC	P12931	735
SKAP1	TLN1	Q9Y490	709
SKAP1	TLN2	Q9Y4G6	706
SKAP1	ZAP70	P43403	704
SKAP1	FERMT3	Q86UX7	698
SKAP1	KNSTRN	Q9Y448	658
SKAP1	NCK1	P16333	610

IntAct

29 interactions, top by confidence:

A	B	Type	Score
FYB1	SKAP1	psi-mi:“MI:0915”(physical association)	0.730
FYB1	SKAP1	psi-mi:“MI:0407”(direct interaction)	0.730
SKAP1	FYB1	psi-mi:“MI:0915”(physical association)	0.730
EEIG1	SKAP1	psi-mi:“MI:0915”(physical association)	0.670
SKAP1	PRAM1	psi-mi:“MI:0915”(physical association)	0.670
SKAP1	EEIG1	psi-mi:“MI:0915”(physical association)	0.670
PRAM1	SKAP1	psi-mi:“MI:0915”(physical association)	0.670
SKAP1	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
SKAP1	SH2D4A	psi-mi:“MI:0915”(physical association)	0.560
SH2D4A	SKAP1	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	SKAP1	psi-mi:“MI:0915”(physical association)	0.560
SKAP1	URI1	psi-mi:“MI:0914”(association)	0.530
FYB1	CKAP5	psi-mi:“MI:0914”(association)	0.350
SKAP1	MYO9A	psi-mi:“MI:0914”(association)	0.350
SKAP1	SKAP2	psi-mi:“MI:0914”(association)	0.350
FYN	SKAP1	psi-mi:“MI:0914”(association)	0.350
GRB2	SKAP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (201): BLCAP (Two-hybrid), SH2D4A (Two-hybrid), PRAM1 (Two-hybrid), FAM102A (Two-hybrid), AP3M1 (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9A (Affinity Capture-MS), POLR1B (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), EML3 (Affinity Capture-MS), WRN (Affinity Capture-MS), ASPM (Affinity Capture-MS), JPH1 (Affinity Capture-MS), POLR1A (Affinity Capture-MS), POLR3A (Affinity Capture-MS)

ESM2 similar proteins: A1L2W9, B2RQE8, B5XG43, G9CGD6, O08969, O88387, P59113, Q0V987, Q0VC85, Q1KKW7, Q1KKZ1, Q32LP0, Q3UUV5, Q3ZBA3, Q4V7G1, Q503L1, Q53GA4, Q5FVW6, Q5PQT7, Q5R8M5, Q5U597, Q5XGP7, Q5ZL23, Q6P0G8, Q6PG29, Q7Z628, Q7Z6J4, Q80VL0, Q80YS6, Q86UX7, Q86WV1, Q8AW35, Q8BY35, Q8IZC4, Q8K1B8, Q8N556, Q8VH46, Q91ZM9, Q91ZT5, Q925E0

Diamond homologs: A1CEK6, A1DFN5, A2QW93, A4FU49, A4RF61, A7A261, A7E3N7, D3ZG83, F1LRS8, O42287, O55043, O60504, O94868, P10569, P19878, P29355, P32793, P38753, P39743, P43603, P49710, P52735, P62993, P62994, P80192, P87379, Q02779, Q06449, Q07883, Q08012, Q08DN7, Q0CJU8, Q0U6X7, Q14155, Q15811, Q16584, Q1E878, Q1KKW7, Q1KKZ1, Q2GT05

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PTPRC	“up-regulates activity”	SKAP1	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3784 predictions. Top by Δscore:

Variant	Effect	Δscore
17:48137194:A:C	donor_gain	1.0000
17:48137227:A:AG	donor_loss	1.0000
17:48137228:C:CT	donor_loss	1.0000
17:48137333:TACTC:T	acceptor_gain	1.0000
17:48137335:CTC:C	acceptor_gain	1.0000
17:48137335:CTCCT:C	acceptor_loss	1.0000
17:48137337:CCT:C	acceptor_loss	1.0000
17:48137338:C:A	acceptor_loss	1.0000
17:48137339:T:C	acceptor_loss	1.0000
17:48180048:TCTCA:T	donor_loss	1.0000
17:48180049:CTCAC:C	donor_loss	1.0000
17:48180050:TCA:T	donor_loss	1.0000
17:48180051:CA:C	donor_loss	1.0000
17:48180052:A:AG	donor_loss	1.0000
17:48180053:C:CA	donor_loss	1.0000
17:48180244:CAGAT:C	acceptor_gain	1.0000
17:48180245:AGAT:A	acceptor_gain	1.0000
17:48180246:GAT:G	acceptor_gain	1.0000
17:48180247:ATCT:A	acceptor_loss	1.0000
17:48180248:TCTA:T	acceptor_loss	1.0000
17:48180249:C:CC	acceptor_gain	1.0000
17:48187841:A:AC	donor_gain	1.0000
17:48187842:C:CC	donor_gain	1.0000
17:48187842:CT:C	donor_gain	1.0000
17:48187842:CTCTT:C	donor_gain	1.0000
17:48345903:AC:A	donor_gain	1.0000
17:48345904:CC:C	donor_gain	1.0000
17:48346003:CCCC:C	acceptor_gain	1.0000
17:48346004:CCCC:C	acceptor_gain	1.0000
17:48346006:CCT:C	acceptor_loss	1.0000

AlphaMissense

2390 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:48137282:A:T	V345D	0.999
17:48182424:A:G	W201R	0.999
17:48182424:A:T	W201R	0.999
17:48182456:A:G	F190S	0.999
17:48184757:A:G	F178S	0.999
17:48187903:A:G	W128R	0.999
17:48187903:A:T	W128R	0.999
17:48182422:C:A	W201C	0.998
17:48182422:C:G	W201C	0.998
17:48189440:A:G	L114S	0.998
17:48187888:A:G	C133R	0.997
17:48187891:A:G	W132R	0.997
17:48187891:A:T	W132R	0.997
17:48187893:C:G	R131P	0.997
17:48187901:C:A	W128C	0.997
17:48187901:C:G	W128C	0.997
17:48182423:C:G	W201S	0.996
17:48182433:C:G	A198P	0.996
17:48182450:G:T	A192D	0.996
17:48182455:A:C	F190L	0.996
17:48182455:A:T	F190L	0.996
17:48182457:A:G	F190L	0.996
17:48184751:A:G	L180P	0.996
17:48184756:A:C	F178L	0.996
17:48184756:A:T	F178L	0.996
17:48184758:A:G	F178L	0.996
17:48189433:C:A	K116N	0.996
17:48189433:C:G	K116N	0.996
17:48137319:A:G	W333R	0.995
17:48137319:A:T	W333R	0.995

dbSNP variants (sampled 300 via entrez): RS1000003060 (17:48192511 T>C), RS1000014850 (17:48248384 T>C), RS1000022996 (17:48402401 C>G), RS1000024058 (17:48338730 G>C), RS1000026622 (17:48439188 A>G), RS1000042179 (17:48347935 T>C), RS1000046811 (17:48197757 G>A), RS1000049553 (17:48439610 C>T), RS1000053314 (17:48395100 C>A,G), RS1000053907 (17:48312640 C>T), RS1000055607 (17:48148073 A>G), RS1000056983 (17:48364606 C>T), RS1000065247 (17:48327440 C>T), RS1000072098 (17:48389913 G>A), RS1000072899 (17:48255002 T>G)

Disease associations

OMIM: gene MIM:604969 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000802_6	Ovarian cancer	1.000000e-06
GCST001662_4	Generalized epilepsy	9.000000e-09
GCST002748_6	Epithelial ovarian cancer	5.000000e-15
GCST002783_122	Body mass index	9.000000e-06
GCST002783_147	Body mass index	4.000000e-07
GCST002783_334	Body mass index	1.000000e-07
GCST004364_15	Intelligence	1.000000e-06
GCST004364_33	Intelligence	3.000000e-08
GCST004904_212	Body mass index	2.000000e-11
GCST006038_6	Food allergy	6.000000e-07
GCST006039_7	Peanut allergy	3.000000e-06
GCST006464_25	Endometrial cancer	5.000000e-09
GCST006465_3	Endometrial cancer (endometrioid histology)	1.000000e-08
GCST006666_17	Lipid traits (pleiotropy) (HIPO component 1)	4.000000e-10
GCST007269_164	Pulse pressure	7.000000e-18
GCST008153_32	Lean body mass	6.000000e-06
GCST010242_441	HDL cholesterol levels	3.000000e-11
GCST90002407_140	White blood cell count	1.000000e-12
GCST90013442_30	Keratoconus	5.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0007016	food allergy measurement
EFO:0007017	peanut allergy measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005763	pulse pressure measurement
EFO:0004995	lean body mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation, increases mutagenesis	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
propionaldehyde	increases expression	1
dimethylselenide	increases expression, increases oxidation	1
beta-lapachone	increases expression	1
sodium arsenite	affects methylation	1
butyraldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
maleic acid	increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Rosiglitazone	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Diuron	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methotrexate	affects response to substance	1
Nickel	increases expression	1
Ozone	increases expression, increases oxidation	1
Phenobarbital	affects expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female
CVCL_D8V5	Ubigene HCT 116 SKAP1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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