CD1A

Summary

CD1A (CD1a molecule, HGNC:1634) is a protein-coding gene on chromosome 1q23.1, encoding T-cell surface glycoprotein CD1a (P06126). Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.

This gene encodes a member of the CD1 family of transmembrane glycoproteins, which are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. The protein encoded by this gene localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 909 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_001763

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1634
Approved symbol	CD1A
Name	CD1a molecule
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000158477
Ensembl biotype	protein_coding
OMIM	188370
Entrez	909

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000289429, ENST00000894721, ENST00000894722

RefSeq mRNA: 2 — MANE Select: NM_001763 NM_001320652, NM_001763

CCDS: CCDS1174

Canonical transcript exons

ENST00000289429 — 6 exons

Exon	Start	End
ENSE00001039139	158256004	158256282
ENSE00001039144	158257421	158257511
ENSE00001075814	158255084	158255350
ENSE00001446468	158257681	158258269
ENSE00001446470	158254424	158254727
ENSE00002381009	158256786	158257064

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 95.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.7753 / max 1031.3562, expressed in 92 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5825	0.6935	17
5830	0.4479	13
5827	0.3676	13
5831	0.2351	15
5829	0.2157	13
5833	0.1451	9
5823	0.1370	26
5828	0.1222	9
5826	0.1190	10
5820	0.0977	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	95.91	gold quality
upper leg skin	UBERON:0004262	94.56	gold quality
skin of hip	UBERON:0001554	92.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.92	gold quality
esophagus squamous epithelium	UBERON:0006920	82.64	gold quality
upper arm skin	UBERON:0004263	82.53	gold quality
epithelium of esophagus	UBERON:0001976	82.18	gold quality
squamous epithelium	UBERON:0006914	79.20	gold quality
gingiva	UBERON:0001828	78.85	silver quality
gingival epithelium	UBERON:0001949	78.33	silver quality
zone of skin	UBERON:0000014	75.94	gold quality
skin of abdomen	UBERON:0001416	75.36	gold quality
monocyte	CL:0000576	74.97	gold quality
mononuclear cell	CL:0000842	74.92	gold quality
leukocyte	CL:0000738	74.60	gold quality
skin of leg	UBERON:0001511	74.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	73.74	gold quality
endometrium epithelium	UBERON:0004811	73.64	gold quality
diaphragm	UBERON:0001103	73.56	gold quality
mammalian vulva	UBERON:0000997	72.38	gold quality
tibialis anterior	UBERON:0001385	71.38	silver quality
oral cavity	UBERON:0000167	70.92	gold quality
tongue squamous epithelium	UBERON:0006919	70.90	gold quality
cervix epithelium	UBERON:0004801	70.73	silver quality
granulocyte	CL:0000094	69.98	gold quality
epithelium of nasopharynx	UBERON:0001951	69.52	gold quality
hair follicle	UBERON:0002073	68.31	gold quality
superficial temporal artery	UBERON:0001614	67.14	gold quality
cervix squamous epithelium	UBERON:0006922	66.63	gold quality
epithelial cell of pancreas	CL:0000083	66.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-79	yes	944.26
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, CREB1, HOXB1, PPARG, SSRP1

miRNA regulators (miRDB)

24 targeting CD1A, 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-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-27B-5P	97.34	66.55	549

Literature-anchored findings (GeneRIF, showing 40)

• outstanding ability of Langerhans cells to mediate CD1a-dependent lipid antigen presentation and thus, Langerhans-cell-mediated skin immunity may involve T cell recognition of both peptide and lipid antigens. (PMID:12925210)
• CD1a and langerin have roles in antigen presentation to T cells (PMID:14991068)
• Review. CD1a on tumor-infiltrating dendritic cells may present immunogenic tumor-specific glycolipid antigens to T-cells. (PMID:15099564)
• CD1a expression was detected on monocytes in the majority of sickle cell anemia patients, and was predominant in SDPunjab patients. (PMID:15556687)
• structural study illustrates how a single chain lipid can be presented by CD1 and that the peptide moiety of the lipopeptide is recognized by the T cell receptor (PMID:15723809)
• hypothesis that CD1-restricted T cells might be activated and home to target tissues involved in Hashimoto’s thyroiditis and Graves’ disease (PMID:15749918)
• CD1a may be a novel biomarker for Barrett metaplasia and that its expression may help to predict the prognosis of this pathology. (PMID:15756258)
• identified CD1a-, CD1b-, and CD1c-restricted T cells from normal human donors that induce cytolysis and secrete copious IFN-gamma in response to self-CD1 expressed on monocyte-derived dendritic cells (PMID:16272286)
• In this study, we show that PTX can selectively block the expression of CD1a isoform during the differentiation of human monocytes into dendritic cells. (PMID:16598657)
• In humans, CD1a-expressing antigen- presenting cells located close to the lymphatic vessels in the upper layers of the dermis may fulfill some of the roles previously ascribed to Langerhans cells. (PMID:16670277)
• A 1000-base pair region upstream of CD1A translation start site is identified as necessary for CD1A proximal promoter activity. (PMID:17082618)
• The mature dentritic cells express CD83 and high CD40/80/86, whereas the immature cells express CD1a and low CD40/80/86 (PMID:17197902)
• Associated with chronic dysimmune neuropathies (PMID:17428545)
• In cystic teratomas of the ovary, CD1-positive Langerhans cells appeared to cross the basal membrane and penetrate the subepidermal tissue, and they were associated there with T-cell line lymphocytes (CD3 positive). (PMID:17652534)
• These findings identify Ii and lipid rafts as key regulators of CD1a organization on the surface of immature DCs and of its immunological function as Ag-presenting molecule. (PMID:18178838)
• The positive and significant correlations between the number of CD1a+ cells and positivity of the primary tumour for estrogen receptor and progesterone receptor suggest a possible role for CD1a as a prognostic marker for breast cancer. (PMID:18184269)
• CD1a expression can be an additional new marker for PEComas and also supports the distinct and integrated disease entity of PEComas. (PMID:18251780)
• HCMV encodes multiple blocking strategies targeting group 1 CD1 molecules CD1a, CD1b, and CD1c (PMID:18287231)
• monocyte-derived DCs cultured in an immunoglobulin-rich milieu expressed CD1d but not CD1a, CD1b, and CD1c, whereas DCs cultured in the presence of low levels of immunoglobulins had an opposite CD1 profile (PMID:18337560)
• Dermal dendritic cells comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages. (PMID:18337829)
• Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules. (PMID:18624350)
• SNPs in CD1A and CD1E were not associated with GBS susceptibility, specific clinical subgroups, anti-ganglioside antibodies, antecedent infections and prognosis. (PMID:18838176)
• Data show high expression of CD86 and CD11C, moderate expression of CD1a and CD123, low levels of CD83 on dendritic cells after induction by GM-CSF and IL-4. (PMID:19257981)
• The quantity of CD1a-positive Langerhans cells in the lesions of epidermodysplasia verruciformis patients was significantly lower than in normal skin. (PMID:19317050)
• CD1a and CD83 may be involved in pain generation and the pathogenesis of endometriosis (PMID:19321495)
• Data show that the expression of CD1a and CD207 is markedly down-regulated in CA epidermis. (PMID:19426597)
• dideoxymycobactin antigens presented by CD1a show T cell fine specificity for natural lipopeptide structures (PMID:19605355)
• The effect of transient stimulation of the canonical Wnt pathway in the differentiation potential of Lin(-)CD34(+) CD1a(-) human thymic progenitors, was analyzed. (PMID:19952356)
• The intracellular trafficking route of CD1a is essential for efficient presentation of lipid antigens that traffic through the early endocytic and recycling pathways. (PMID:20026739)
• microsomal triglyceride transfer protein deficiency was associated with increased proteasomal degradation of group 1 CD1 molecules in human abetalipoproteinemia. (PMID:20592474)
• Accumulation of CD1a-positive Langerhans cells and mast cells in actinic cheilitis. (PMID:20890667)
• CD1E and CD1A genes may be involved in networks which determine susceptibility to multiple sclerosis types RR-MS and PP-MS, respectively. (PMID:20954848)
• We do not believe that there is a role for CD1a immunohistochemistry in the differential diagnosis of perivascular epithelioid cell neoplasms. (PMID:21194729)
• CD1A and CD1E polymorphisms contribute to the polygenic susceptibility to multiple sclerosis (PMID:21496400)
• In Guillain-Barre syndrome, an initially positive association study with polymorphism of CD1A and CD1E genes was not confirmed (PMID:21696499)
• GM-CSF independent signaling directed toward the CD1a genome is important in Langerhans cell biology. (PMID:21900947)
• allelic variation in CD1A does not play a major role in determining multifocal motor neuropathy susceptibility. (PMID:22003931)
• In the intratumoral and peritumoral areas, the expression of CD1a, tryptase, and CD68 was significantly higher in papillary thyroid carcinoma than in thyroid adenomas. (PMID:22007938)
• Saposins utilize two strategies for lipid transfer and CD1 antigen presentation (PMID:22331868)
• these results reveal that CD1 expression is modified in MS and provide novel information on the regulation of lipid antigen presentation in myeloid cells. (PMID:22670773)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	mhc1laa	ENSDARG00000016056
danio_rerio	mhc1lba	ENSDARG00000016227
danio_rerio	mhc1lda	ENSDARG00000023203
danio_rerio		ENSDARG00000051710
danio_rerio		ENSDARG00000051711
danio_rerio	mhc1lfa	ENSDARG00000051712
danio_rerio	mhc1lga	ENSDARG00000051713
danio_rerio	mhc1lca	ENSDARG00000055813
danio_rerio	mhc1lja	ENSDARG00000096830
danio_rerio	si:dkey-52p2.5	ENSDARG00000096940
danio_rerio	mhc1lla	ENSDARG00000096977

Paralogs (22): HFE (ENSG00000010704), FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP2 (ENSG00000131015), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), RAET1L (ENSG00000155918), CD1D (ENSG00000158473), CD1C (ENSG00000158481), CD1B (ENSG00000158485), CD1E (ENSG00000158488), AZGP1 (ENSG00000160862), RAET1E (ENSG00000164520), RAET1G (ENSG00000203722), MICB (ENSG00000204516), MICA (ENSG00000204520), HLA-C (ENSG00000204525), HLA-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503), HLA-B (ENSG00000234745)

Protein

Protein identifiers

T-cell surface glycoprotein CD1a — P06126 (reviewed: P06126)

Alternative names: T-cell surface antigen T6/Leu-6

All UniProt accessions (1): P06126

UniProt curated annotations — full annotation on UniProt →

Function. Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.

Subunit / interactions. Heterodimer with B2M (beta-2-microglobulin). Interacts with CD74.

Subcellular location. Cell membrane. Membrane raft. Endosome membrane.

Tissue specificity. Expressed on cortical thymocytes, epidermal Langerhans cells, dendritic cells, on certain T-cell leukemias, and in various other tissues.

Miscellaneous. During protein synthesis and maturation, CD1 family members bind endogenous lipids that are replaced by lipid or glycolipid antigens when the proteins are internalized and pass through endosomes, before trafficking back to the cell surface.

RefSeq proteins (2): NP_001307581, NP_001754* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily
IPR050208	MHC_class-I_related	Family

Pfam: PF07654, PF16497

UniProt features (47 total): strand 16, helix 9, glycosylation site 4, sequence variant 3, turn 3, binding site 3, disulfide bond 2, topological domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
5J1A	X-RAY DIFFRACTION	1.86
4X6F	X-RAY DIFFRACTION	1.91
7SH4	X-RAY DIFFRACTION	2
7KP1	X-RAY DIFFRACTION	2.02
4X6E	X-RAY DIFFRACTION	2.1
9OHZ	X-RAY DIFFRACTION	2.14
1ONQ	X-RAY DIFFRACTION	2.15
6NUX	X-RAY DIFFRACTION	2.2
7KOZ	X-RAY DIFFRACTION	2.25
7KP0	X-RAY DIFFRACTION	2.4
7RYN	X-RAY DIFFRACTION	2.7
1XZ0	X-RAY DIFFRACTION	2.8
4X6C	X-RAY DIFFRACTION	2.8
4X6D	X-RAY DIFFRACTION	2.98
7RYO	X-RAY DIFFRACTION	3
7RYM	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06126-F1	89.11	0.77

Functional residue map

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

Ligand- & substrate-binding residues (3): 90–94; 171; 175

Disulfide bonds (2): 119–183, 223–278

Glycosylation sites (4): 60, 74, 145, 37

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 124 (showing top): GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_255, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MODULE_317, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_VIA_MHC_CLASS_IB, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_POSITIVE_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GOBP_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY, GOBP_REGULATION_OF_LYMPHOCYTE_MEDIATED_IMMUNITY

GO Biological Process (6): positive regulation of T cell mediated cytotoxicity (GO:0001916), adaptive immune response (GO:0002250), immune response (GO:0006955), antigen processing and presentation, endogenous lipid antigen via MHC class Ib (GO:0048006), antigen processing and presentation, exogenous lipid antigen via MHC class Ib (GO:0048007), immune system process (GO:0002376)

GO Molecular Function (4): endogenous lipid antigen binding (GO:0030883), exogenous lipid antigen binding (GO:0030884), lipopeptide binding (GO:0071723), protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endosome membrane (GO:0010008), membrane raft (GO:0045121), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antigen processing and presentation of lipid antigen via MHC class Ib	2
lipid antigen binding	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of T cell mediated immunity	1
immune response	1
immune system process	1
response to stimulus	1
antigen processing and presentation of endogenous antigen	1
antigen processing and presentation of exogenous antigen	1
biological_process	1
lipid binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
membrane microdomain	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD1A	CD207	Q9UJ71	937
CD1A	CD68	P34810	903
CD1A	CD83	Q01151	879
CD1A	CD86	P42081	790
CD1A	CD80	P33681	786
CD1A	CD4	P01730	784
CD1A	ITGAX	P20702	779
CD1A	CD5	P06127	769
CD1A	MME	P08473	744
CD1A	CSF2	P04141	730
CD1A	CD34	P28906	724
CD1A	CD7	P09564	723
CD1A	CD8A	P01732	720
CD1A	B2M	P01884	720
CD1A	CD40	P25942	716

IntAct

8 interactions, top by confidence:

A	B	Type	Score
B2M	CD1A	psi-mi:“MI:0407”(direct interaction)	0.620
CD1A	DGAT1	psi-mi:“MI:0915”(physical association)	0.370
KCTD5	CD1A	psi-mi:“MI:0915”(physical association)	0.370
UBTD1	CD1A	psi-mi:“MI:0915”(physical association)	0.370
CD1A	EXTL3	psi-mi:“MI:0914”(association)	0.350
CD1A	FZD6	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): KCNJ8 (Affinity Capture-MS), PURB (Affinity Capture-MS), EXTL3 (Affinity Capture-MS), RAB3B (Affinity Capture-MS), WNT5A (Affinity Capture-MS), CPT1A (Affinity Capture-MS), SUSD1 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), INTS7 (Affinity Capture-MS), RNF167 (Affinity Capture-MS), MAN1A2 (Affinity Capture-MS), TMEM120A (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM67 (Affinity Capture-MS), C1QL4 (Affinity Capture-MS)

ESM2 similar proteins: O35799, O62848, P01898, P01899, P06126, P06339, P10321, P11609, P11610, P13747, P13752, P13753, P14429, P14430, P15812, P15813, P15978, P16212, P16215, P17693, P23043, P29016, P29017, P30511, P30515, P30516, P30517, P60018, P70387, Q28565, Q29422, Q30201, Q3ZCH5, Q4ACW4, Q5YB65, Q63493, Q95IT1, Q95IT3, Q9GKZ0, Q9GL41

Diamond homologs: C1ITJ8, O19477, O35799, P01888, P01889, P01893, P01894, P01895, P01896, P01897, P01898, P01899, P01900, P01901, P01902, P03991, P04223, P04439, P06126, P06140, P06339, P10321, P13747, P13748, P13749, P13750, P13751, P13752, P13753, P13765, P14426, P14427, P14428, P14429, P14430, P14431, P14432, P15464, P15978, P15979

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

789 predictions. Top by Δscore:

Variant	Effect	Δscore
1:158255347:GAAT:G	donor_gain	1.0000
1:158255351:G:GG	donor_gain	1.0000
1:158257076:C:G	donor_gain	1.0000
1:158255315:G:T	donor_gain	0.9900
1:158255349:ATGTG:A	donor_loss	0.9900
1:158255350:TGT:T	donor_loss	0.9900
1:158255351:G:C	donor_loss	0.9900
1:158256784:A:AG	acceptor_gain	0.9900
1:158256785:G:GG	acceptor_gain	0.9900
1:158257101:G:GT	donor_gain	0.9900
1:158255353:GAG:G	donor_loss	0.9800
1:158255354:AGTT:A	donor_loss	0.9800
1:158257062:GGG:G	donor_gain	0.9800
1:158257063:GGG:G	donor_gain	0.9800
1:158257412:A:G	acceptor_gain	0.9800
1:158257419:A:AG	acceptor_gain	0.9800
1:158257420:G:GG	acceptor_gain	0.9800
1:158257679:A:AG	acceptor_gain	0.9800
1:158257680:G:GG	acceptor_gain	0.9800
1:158255349:AT:A	donor_gain	0.9700
1:158255356:T:G	donor_gain	0.9700
1:158257411:A:AG	acceptor_gain	0.9700
1:158257420:GA:G	acceptor_gain	0.9700
1:158257420:GAGC:G	acceptor_gain	0.9700
1:158255265:G:GT	donor_gain	0.9600
1:158255269:G:GT	donor_gain	0.9600
1:158256785:GTGAA:G	acceptor_gain	0.9600
1:158255082:AG:A	acceptor_gain	0.9500
1:158255083:GG:G	acceptor_gain	0.9500
1:158255314:GGAA:G	donor_gain	0.9500

AlphaMissense

2145 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:158256863:T:C	F228L	0.984
1:158256865:C:A	F228L	0.984
1:158256865:C:G	F228L	0.984
1:158256892:G:C	W237C	0.969
1:158256892:G:T	W237C	0.969
1:158256890:T:A	W237R	0.947
1:158256890:T:C	W237R	0.947
1:158256848:T:A	C223S	0.946
1:158256849:G:C	C223S	0.946
1:158257013:T:A	C278S	0.933
1:158257014:G:C	C278S	0.933
1:158257031:A:C	S284R	0.933
1:158257033:T:A	S284R	0.933
1:158257033:T:G	S284R	0.933
1:158257027:C:A	H282Q	0.928
1:158257027:C:G	H282Q	0.928
1:158256864:T:C	F228S	0.922
1:158256848:T:C	C223R	0.918
1:158256855:T:A	V225D	0.908
1:158257013:T:C	C278R	0.898
1:158256850:C:G	C223W	0.897
1:158256864:T:G	F228C	0.897
1:158255221:T:C	F66L	0.896
1:158255223:C:A	F66L	0.896
1:158255223:C:G	F66L	0.896
1:158256792:C:A	P204H	0.891
1:158256849:G:A	C223Y	0.888
1:158255233:T:A	W70R	0.873
1:158255233:T:C	W70R	0.873
1:158257014:G:A	C278Y	0.871

dbSNP variants (sampled 300 via entrez): RS1000052954 (1:158256688 A>G), RS1000082017 (1:158256438 G>T), RS1000356398 (1:158250727 T>A,C), RS1000700659 (1:158246652 T>C), RS1000960106 (1:158252051 G>A), RS1001006855 (1:158252322 G>A), RS1001298993 (1:158246596 T>C), RS1001326809 (1:158252250 G>A), RS1001340589 (1:158253868 G>C,T), RS1001539066 (1:158249543 A>G), RS1001566079 (1:158258124 C>T), RS1001998295 (1:158249822 G>A,C), RS1002840376 (1:158249783 G>A), RS1003256486 (1:158248576 C>T), RS1003424534 (1:158254060 T>G)

Disease associations

OMIM: gene MIM:188370 | disease phenotypes: MIM:605373, MIM:606764, MIM:608266

GenCC curated gene-disease

Mondo (3): pheochromocytoma/paraganglioma syndrome 3 (MONDO:0011544), gastrointestinal stromal tumor (MONDO:0011719), parathyroid gland carcinoma (MONDO:0012004)

Orphanet (3): Parathyroid carcinoma (Orphanet:143), Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Gastrointestinal stromal tumor (Orphanet:44890)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008497_1	Change in neurofilament light levels	5.000000e-08
GCST009269_21	Dental caries (decayed and filled deciduous teeth)	3.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D046152	Gastrointestinal Stromal Tumors	C04.557.450.565.370; C06.301.371.308; C06.405.249.308
C565335	Paragangliomas 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Rosiglitazone	affects cotreatment, decreases expression, decreases reaction	2
Lipopolysaccharides	affects cotreatment, decreases reaction, increases expression, decreases expression	2
sodium arsenite	affects cotreatment, decreases reaction, increases expression	1
24,25-epoxycholesterol	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
3,5-di-tert-butylchalcone 4’-carboxylic acid	decreases expression	1
Am 580	decreases expression	1
MF59 oil emulsion	increases expression, affects cotreatment, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
HX 630	decreases expression, decreases reaction	1
2-chloro-5-nitrobenzanilide	decreases reaction, decreases expression	1
lupane	increases expression	1
lipopolysaccharide, E coli O55-B5	decreases expression	1
Alitretinoin	decreases expression, decreases reaction, affects cotreatment	1
Acetaminophen	decreases expression	1
Allergens	increases expression, affects cotreatment, increases abundance	1
Alum Compounds	increases expression, affects cotreatment, decreases reaction	1
Aluminum Hydroxide	affects cotreatment, decreases reaction, increases expression	1
Arsenic	affects expression, increases abundance	1
Vehicle Emissions	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cacodylic Acid	affects expression, increases abundance	1
Cadmium	decreases expression	1
Methotrexate	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7V8	Abcam Jurkat CD1A KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00171977	PHASE4	COMPLETED	Post-Marketing Clinical Study of Postoperative Adjuvant Therapy With Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT00510354	PHASE4	COMPLETED	Treatment of Patients With Everolimus and Imatinib Mesylate Who Have Progressive Gastro Intestinal Stromal Tumors (GIST) and Are Resistant to Imatinib Mesylate
NCT00756509	PHASE4	COMPLETED	Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT02800330	PHASE4	COMPLETED	The Effects of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib
NCT04825574	PHASE4	COMPLETED	Study for Patients Previously Treated in Avapritinib Clinical Trials
NCT00009906	PHASE3	TERMINATED	Comparison of Two Different Doses of STI571 in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
NCT00041197	PHASE3	COMPLETED	Imatinib Mesylate in Treating Patients With Primary Gastrointestinal Stromal Tumor That Has Been Completely Removed By Surgery
NCT00075218	PHASE3	COMPLETED	A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)
NCT00103168	PHASE3	COMPLETED	Imatinib Mesylate or Observation Only in Treating Patients Who Have Undergone Surgery for Localized Gastrointestinal Stromal Tumor
NCT00293124	PHASE3	COMPLETED	Open-label Trial of GlivecWith Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumors
NCT00324987	PHASE3	TERMINATED	Imatinib Mesylate With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
NCT00372567	PHASE3	TERMINATED	Safety And Effectiveness Of Daily Dosing With Sunitinib Or Imatinib In Patients With Gastrointestinal Stromal Tumors
NCT00471328	PHASE3	COMPLETED	Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib
NCT00685828	PHASE3	UNKNOWN	Imatinib Mesylate in Treating Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumor
NCT00688766	PHASE3	TERMINATED	Study Evaluating IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) Following Failure of at Least Imatinib and Sunitinib
NCT00751036	PHASE3	TERMINATED	Nilotinib 800 Mg And Imatinib 800 Mg For The Treatment Of Patients With Gastrointestinal Stromal Tumors (Gist) Refractory To Imatinib 400 Mg
NCT00785785	PHASE3	COMPLETED	A Study of Nilotinib Versus Imatinib in GIST Patients
NCT00812240	PHASE3	TERMINATED	Masitinib in First Line Treatment of Gastro-Intestinal Stromal Tumor (GIST)
NCT00956072	PHASE3	TERMINATED	Imatinib Mesylate With or Without Surgery in Treating Patients With Metastatic Gastrointestinal Stromal Tumor That is Responding to Imatinib Mesylate
NCT01031628	PHASE3	TERMINATED	Study of Dose Escalation Versus no Dose Escalation of Imatinib in Metastatic Gastrointestinal Stromal Tumors (GIST) Patients
NCT01151852	PHASE3	COMPLETED	Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT
NCT01265810	PHASE3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01271712	PHASE3	COMPLETED	Study of Regorafenib as a 3rd-line or Beyond Treatment for Gastrointestinal Stromal Tumors (GIST)
NCT01289028	PHASE3	COMPLETED	Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.
NCT01462994	PHASE3	COMPLETED	Detection of CF-DNA in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT01694277	PHASE3	COMPLETED	Masitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib
NCT02260505	PHASE3	COMPLETED	Efficiency of Imatinib Treatment Maintenance or Interruption After 3 Years of Adjuvant Treatment in Patients With Gastrointestinal Stromal Tumours (GIST)
NCT02576080	PHASE3	UNKNOWN	Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index
NCT02866045	PHASE3	UNKNOWN	EUS-FNB vs. Single-incision Needle-knife (SINK) Biopsy for Gastrointestinal SELs
NCT03353753	PHASE3	COMPLETED	Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies
NCT03426722	PHASE3	COMPLETED	L-carnitine vs Placebo for the Treatment of Muscle Cramps After Imatinib in Gastrointestinal Stromal Tumors
NCT03465722	PHASE3	COMPLETED	(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST
NCT03673501	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib
NCT04409223	PHASE3	TERMINATED	Efficacy and Safety of Famitinib Versus Sunitinib in the Treatment of Advanced Gastrointestinal Stromal Tumour Patients After Failure of Imatinib
NCT05208047	PHASE3	ACTIVE_NOT_RECRUITING	(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
NCT05734105	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib
NCT06640361	PHASE3	RECRUITING	A Study of Olverembatinib in SDH-deficient GIST.
NCT07585266	PHASE3	NOT_YET_RECRUITING	A Study to Investigate Velzatinib Compared With Imatinib in Adult Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (StrateGIST Frontline)
NCT00003939	PHASE2	COMPLETED	Ecteinascidin 743 in Treating Patients With Advanced Soft Tissue Sarcoma