CD99

Summary

CD99 (CD99 molecule (Xg blood group), HGNC:7082) is a protein-coding gene on chromosome Xp22.32 and Yp11.3, encoding CD99 antigen (P14209). Involved in T-cell adhesion processes and in spontaneous rosette formation with erythrocytes.

The protein encoded by this gene is a cell surface glycoprotein involved in leukocyte migration, T-cell adhesion, ganglioside GM1 and transmembrane protein transport, and T-cell death by a caspase-independent pathway. In addition, the encoded protein may have the ability to rearrange the actin cytoskeleton and may also act as an oncosuppressor in osteosarcoma. This gene is found in the pseudoautosomal region of chromosomes X and Y and escapes X-chromosome inactivation. There is a related pseudogene located immediately adjacent to this locus.

Source: NCBI Gene 4267 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 174 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_002414

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7082
Approved symbol	CD99
Name	CD99 molecule (Xg blood group)
Location	Xp22.32 and Yp11.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000002586
Ensembl biotype	protein_coding
OMIM	313470, 450000
Entrez	4267

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 32 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000381177, ENST00000381180, ENST00000381184, ENST00000381187, ENST00000381192, ENST00000449611, ENST00000482293, ENST00000482405, ENST00000497752, ENST00000611428, ENST00000623253, ENST00000624481, ENST00000645950, ENST00000646103, ENST00000647297, ENST00000863832, ENST00000863833, ENST00000863834, ENST00000863835, ENST00000863836, ENST00000863837, ENST00000863838, ENST00000863839, ENST00000863840, ENST00000863841, ENST00000863842, ENST00000863843, ENST00000863844, ENST00000863845, ENST00000863846, ENST00000928650, ENST00000928653, ENST00000928655, ENST00000928657, ENST00000928659, ENST00000928660, ENST00000928661, ENST00000928662, ENST00000957177, ENST00000957178

RefSeq mRNA: 6 — MANE Select: NM_002414 NM_001122898, NM_001321367, NM_001321368, NM_001321369, NM_001321370, NM_002414

CCDS: CCDS14119, CCDS48071, CCDS75947, CCDS83452

Canonical transcript exons

ENST00000381192 — 10 exons

Exon	Start	End
ENSE00001032174	2738200	2738256
ENSE00001487771	2740779	2741309
ENSE00001487792	2691295	2691427
ENSE00003474982	2717605	2717652
ENSE00003535342	2714422	2714454
ENSE00003552837	2722627	2722674
ENSE00003578821	2720356	2720424
ENSE00003586106	2719661	2719705
ENSE00003612985	2723314	2723364
ENSE00003785141	2726260	2726373

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 125.3468 / max 1940.3431, expressed in 627 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195367	55.4029	625
195366	29.6311	617
195364	17.2319	609
195363	15.9459	615
195362	4.9265	612
195365	1.9473	500
195371	0.2613	163

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	99.89	gold quality
thymus	UBERON:0002370	99.71	gold quality
stromal cell of endometrium	CL:0002255	99.58	gold quality
synovial joint	UBERON:0002217	99.58	gold quality
islet of Langerhans	UBERON:0000006	99.55	gold quality
olfactory bulb	UBERON:0002264	99.55	gold quality
tendon of biceps brachii	UBERON:0008188	99.55	gold quality
layer of synovial tissue	UBERON:0007616	99.50	gold quality
right coronary artery	UBERON:0001625	99.49	gold quality
vena cava	UBERON:0004087	99.48	gold quality
tibial nerve	UBERON:0001323	99.45	gold quality
urethra	UBERON:0000057	99.44	gold quality
descending thoracic aorta	UBERON:0002345	99.43	gold quality
left coronary artery	UBERON:0001626	99.41	gold quality
saphenous vein	UBERON:0007318	99.41	gold quality
coronary artery	UBERON:0001621	99.40	gold quality
popliteal artery	UBERON:0002250	99.40	gold quality
cauda epididymis	UBERON:0004360	99.40	gold quality
tibial artery	UBERON:0007610	99.40	gold quality
aorta	UBERON:0000947	99.39	gold quality
thoracic aorta	UBERON:0001515	99.39	gold quality
ascending aorta	UBERON:0001496	99.38	gold quality
body of uterus	UBERON:0009853	99.37	gold quality
endocervix	UBERON:0000458	99.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.36	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.35	gold quality
right lung	UBERON:0002167	99.34	gold quality
periodontal ligament	UBERON:0008266	99.33	gold quality
ectocervix	UBERON:0012249	99.32	gold quality
lower esophagus	UBERON:0013473	99.32	gold quality

Single-cell (SCXA)

Detected in 36 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	4141.51
E-MTAB-5061	yes	3217.73
E-CURD-112	yes	2033.92
E-MTAB-9154	yes	1338.94
E-MTAB-9067	yes	1254.31
E-HCAD-6	yes	1155.79
E-HCAD-4	yes	134.83
E-CURD-122	yes	57.13
E-HCAD-1	yes	44.88
E-MTAB-6701	yes	43.86
E-HCAD-31	yes	40.74
E-HCAD-10	yes	37.30
E-HCAD-5	yes	35.77
E-MTAB-8410	yes	34.86
E-GEOD-81547	yes	31.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF4, EWSR1, FLI1, NFKB1, NFKB2, NFKB, SP1

miRNA regulators (miRDB)

12 targeting CD99, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-365A-5P	94.91	63.72	471
HSA-MIR-365B-5P	94.91	63.79	470
HSA-MIR-4474-5P	94.23	67.95	568
HSA-MIR-4508	90.37	59.62	240

Literature-anchored findings (GeneRIF, showing 40)

• Results suggest that type I is the major isoform of CD99 expressed in non-neoplastic gastric mucosa and gastric adenocarcinomas. (PMID:12172043)
• Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells (PMID:12216109)
• engagement triggers the exocytic transport of ganglioside GM1 and the reorganization of actin cytoskeleton (PMID:12681511)
• inhibition by MHC class I engagement or apoptosis and upregulation of T cell receptor and MHC molecules in human thymocytes and T cell line induced by CD99 (PMID:12832073)
• CD99 epitopes plays a distinct role in T cell biology, especially in T cell apoptosis. (PMID:14623115)
• CD99 type II acts as a negative regulator in the neural differentiation of precursor cells that might occur during nerve system development (PMID:14646598)
• Solitary sclerotic fibroma is a fibrotic lesion with cells positive for CD34 and O13. O13 expression in SF has not been previously described. (PMID:14744088)
• our findings indicate that CD99 functions occur through reorganization of cytoskeleton and identify actin and zyxin as the early signaling events driven by CD99 engagement. (PMID:15184883)
• solution structure of cytoplasmic domain of human CD99 type I shows that it has a hairpin shape anchored by two flexible loops (PMID:15359120)
• cyclophilin A binds CD99 and may be either a signaling mediator or a signaling regulator for CD99 (PMID:15388255)
• loss of CD99 expression in PETs was found to be associated with ominous prognostic indicators (PMID:15469477)
• Cooperation of CD99 engagement with suboptimal TCR/CD3 signals resulted in enhanced CD4+ T cell proliferation, elevated expression of CD25 and GM1, increased apoptosis, augmented activation of JNK, and increased AP-1 activation (PMID:15528994)
• CD99 was found to be widely expressed in both sarcomatous and carcinoma component in pleomorphic carcinomas of the lung (PMID:15716602)
• High expression of CD99 in ALK-positive anaplastic large cell lymphomas is an unexpected finding and its biologic and clinical significance has yet to be clarified. (PMID:16361803)
• The findings point to an antioncogenic role for CD99 in osteosarcoma, likely through the regulation of caveolin-1 and inhibition of c-Src kinase activity. (PMID:16421247)
• LMP-1 induced down-regulation of the CD99 pathway is important in nasopharyngeal carcinogenesis, and the expression of CD99 in lymphoid stroma may regulate immune response to nasopharyngeal carcinoma. (LMP-1= EBV latent membrane protein 1) (PMID:16614706)
• subsets of CD34+ cells with high or low levels of CD99 expression produce different numbers of erythroid, natural killer (NK), or dendritic cells in the in vitro differentiation assays (PMID:16825498)
• The results of this study suggest that expression of a splice variant of CD99 contributes to the invasive ability of human breast cancer cells by up-regulating AP-1-mediated gene expression through the Akt-dependent ERK and JNK signaling pathways. (PMID:16984917)
• PECAM (CD31) and CD99 regulate distinct, sequential steps in the transendothelial migration of neutrophils during inflammation (PMID:17202377)
• These data demonstrate the unique properties of CD99 co-stimulation that distinguish this molecule from CD28 and other raft-resident co-stimulatory factors. (PMID:17464179)
• Our findings highlight the involvement of CD99 in crucial processes of cancer malignancy. (PMID:17471235)
• CK19/CD99 immunoexpression did not correlate with extent of tumor invasion, mitotic activity, Ki-67 labeling index, presence of extracellular mucinous pools dissecting muscle, and angiolymphatic and perineural/neural invasion in goblet cell carcinoids. (PMID:17652531)
• CD99-immunohistochemistry is unique in that it is helpful for the diagnosis of clear cell brain tumors through the visualization of CD99-negative clear cells (PMID:18552083)
• CD99 also binds p230/golgin-245, a coiled-coil protein that recycles between the cytosol and buds/vesicles of the TGN and which plays a fundamental role in trafficking transport vesicles. (PMID:18849489)
• CD99 is frequently expressed in anaplastic large cell lymphoma (PMID:19289593)
• CD99 plays a critical role in human monocyte and lymphocyte transendothelial migration across pocine endothelial cells. (PMID:19307784)
• Type B3 thymic epithelial tumor in an adolescent detected by immunohistochemical staining for CD5, CD99, and KIT (CD117): a case report. (PMID:19901887)
• CD99 showed no preferential staining of Atypical fibroxanthoma, spindle cell malignant melanoma or sarcomatoid carcinoma/spindle cell squamous cell carcinoma (PMID:20184665)
• Analysis of a panel of human EWS cells revealed an inverse correlation between CD99 and H-neurofilament expression, as well as an inverse correlation between neural differentiation and oncogenic transformation. (PMID:20197622)
• Protein expression and gene promoter hypermethylation of CD99 in transitional cell carcinoma of urinary bladder (PMID:20217126)
• CD99 may play a physiologic role in the clonal deletion processes necessary for B-lymphoid selection (PMID:20453109)
• CD99 positivity was significantly associated with advanced stage (p < 0.01), higher risk group according to the International Prognostic Index risk score (p < 0.01) and non-germinal center B cell-like type (p = 0.01). (PMID:21196719)
• High CD99 is associated with central primitive neuroectodermal tumors and Ewing’s sarcoma (PMID:21267687)
• Our study has identified for the first time that pancreatic solid-pseudopapillary neoplasm exhibits a unique dot-like staining pattern for CD99. (PMID:21566515)
• Data show that CD99 combined with E-cadherin/beta-catenin and CD10 can be used as a relatively specific expression profile of SPTs. (PMID:21775056)
• upregulation of CD99 in H/RS cells induces terminal B-cell differentiation, which may provide a novel therapeutic strategies for cHL (PMID:22020966)
• NF-kappaB2 exhibits the major inhibitory role in the transcription at the CD99 promoter (PMID:22083306)
• Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and CD99 are critical in lymphatic transmigration of human dendritic cells. (PMID:22189791)
• The new antibody scFvC7 recognizes the CD99 extracellular domain. (PMID:22335486)
• the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression. (PMID:22392539)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd99	ENSDARG00000051975
rattus_norvegicus		ENSRNOG00000072482

Paralogs (1): CD99L2 (ENSG00000102181)

Protein

Protein identifiers

CD99 antigen — P14209 (reviewed: P14209)

Alternative names: 12E7, E2 antigen, Protein MIC2, T-cell surface glycoprotein E2

All UniProt accessions (5): P14209, A0A096LP69, A6NGF6, A6NJT9, A8MQT7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in T-cell adhesion processes and in spontaneous rosette formation with erythrocytes. Plays a role in a late step of leukocyte extravasation helping leukocytes to overcome the endothelial basement membrane. Acts at the same site as, but independently of, PECAM1. Involved in T-cell adhesion processes.

Subcellular location. Membrane.

Post-translational modifications. Extensively O-glycosylated.

Miscellaneous. The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes.

Similarity. Belongs to the CD99 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P14209-1	I	yes
P14209-2	II
P14209-3	3

RefSeq proteins (6): NP_001116370, NP_001308296, NP_001308297, NP_001308298, NP_001308299, NP_002405* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022078	CD99L2	Family

Pfam: PF12301

UniProt features (17 total): compositionally biased region 4, modified residue 2, splice variant 2, sequence variant 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7SFX	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14209-F1	60.43	0.03

Antibody-complex structures (SAbDab): 1 — 7SFX

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 (2): 168, 181

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 236 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, HARRIS_HYPOXIA, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_CELLULAR_EXTRAVASATION, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_CELL_CELL_ADHESION, GOBP_CELLULAR_EXTRAVASATION, GOBP_LEUKOCYTE_MIGRATION, GOBP_POSITIVE_REGULATION_OF_NEUTROPHIL_MIGRATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_MIGRATION, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN

GO Biological Process (4): homotypic cell-cell adhesion (GO:0034109), T cell extravasation (GO:0072683), positive regulation of neutrophil extravasation (GO:2000391), cell adhesion (GO:0007155)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Adaptive Immune System	1
Hemostasis	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell-cell adhesion	1
cellular extravasation	1
T cell migration	1
positive regulation of cellular extravasation	1
neutrophil extravasation	1
positive regulation of neutrophil migration	1
regulation of neutrophil extravasation	1
cellular process	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell-substrate junction	1

Protein interactions and networks

STRING

1066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD99	ICAM1	P05362	975
CD99	EWSR1	Q01844	943
CD99	PILRA	Q9UKJ1	919
CD99	XG	P55808	860
CD99	CD99L2	Q8TCZ2	849
CD99	CD34	P28906	840
CD99	SYP	P08247	819
CD99	ENO2	P09104	812
CD99	ARSF	P54793	789
CD99	SHOX	O15266	777
CD99	STS	P08842	775
CD99	PECAM1	P16284	775
CD99	PILRB	Q9UKJ0	759
CD99	PTPRC	P08575	741
CD99	ETV4	P43268	731

IntAct

40 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CD99	sepZ	psi-mi:“MI:0915”(physical association)	0.370
CD99	SGTA	psi-mi:“MI:0915”(physical association)	0.370
CD99	UBQLN1	psi-mi:“MI:0915”(physical association)	0.370
	CD99	psi-mi:“MI:0915”(physical association)	0.370
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
CD81	CD276	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC16A1	STXBP3	psi-mi:“MI:0914”(association)	0.350
CAPRIN1	VPS37C	psi-mi:“MI:0914”(association)	0.350
PXN	SDCBP	psi-mi:“MI:0914”(association)	0.350
PXN	IRS4	psi-mi:“MI:0914”(association)	0.350
TSC22D3	VPS37C	psi-mi:“MI:0914”(association)	0.350
UCHL1	SNAP23	psi-mi:“MI:0914”(association)	0.350
CAPN1	ATG7	psi-mi:“MI:0914”(association)	0.350
OSBPL11	DNM1L	psi-mi:“MI:0914”(association)	0.350
RAE1	NHERF1	psi-mi:“MI:0914”(association)	0.350
SLC19A3	SNAP23	psi-mi:“MI:0914”(association)	0.350
SLC7A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SPAST	SDCBP	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (93): UBQLN1 (Two-hybrid), CD99 (Proximity Label-MS), CD99 (Proximity Label-MS), CD99 (Proximity Label-MS), CD99 (Two-hybrid), CD99 (Two-hybrid), CD99 (Affinity Capture-RNA), CD99 (Proximity Label-MS), CD99 (Proximity Label-MS), CD99 (Affinity Capture-MS), CD99 (Affinity Capture-MS), CD99 (Affinity Capture-MS), CD99 (Protein-RNA), CD99 (Proximity Label-MS), CD99 (Proximity Label-MS)

ESM2 similar proteins: A1A4K1, B1H3G4, E9PV24, O35988, O61704, O75167, O93383, P14209, P14599, P15514, P24338, P31431, P31955, P34741, P34900, P34901, P43322, P43407, P49414, P49416, P50605, P55808, P58239, Q02297, Q0VFF9, Q1RMT9, Q27913, Q56A20, Q58DD4, Q5RAT9, Q5RCS3, Q5RE35, Q5REP3, Q5XG99, Q6DBW9, Q6GR51, Q6PKG0, Q6ZQ58, Q7SXB3, Q7TMJ8

Diamond homologs: A1A4K1, B1H3G4, P14209, Q5RE35, Q6DBW9, Q8BIF0, Q8R1R5, Q8TCZ2, Q8VCN6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	3
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
488031	Single allele	Likely pathogenic

SpliceAI

1882 predictions. Top by Δscore:

Variant	Effect	Δscore
X:2714417:CTTAG:C	acceptor_loss	1.0000
X:2714418:TTA:T	acceptor_loss	1.0000
X:2714419:TAG:T	acceptor_loss	1.0000
X:2714420:AGAT:A	acceptor_gain	1.0000
X:2714421:G:GC	acceptor_loss	1.0000
X:2714421:GATG:G	acceptor_gain	1.0000
X:2717744:G:GT	donor_gain	1.0000
X:2719658:TAG:T	acceptor_loss	1.0000
X:2719659:A:AG	acceptor_gain	1.0000
X:2719659:AG:A	acceptor_gain	1.0000
X:2719659:AGG:A	acceptor_gain	1.0000
X:2719659:AGGG:A	acceptor_gain	1.0000
X:2719659:AGGGG:A	acceptor_loss	1.0000
X:2719660:G:GA	acceptor_gain	1.0000
X:2719660:GG:G	acceptor_gain	1.0000
X:2719660:GGG:G	acceptor_gain	1.0000
X:2719660:GGGG:G	acceptor_gain	1.0000
X:2719701:AAATG:A	donor_gain	1.0000
X:2719702:AATG:A	donor_gain	1.0000
X:2719703:ATG:A	donor_gain	1.0000
X:2719704:TG:T	donor_gain	1.0000
X:2719704:TGG:T	donor_loss	1.0000
X:2719705:GG:G	donor_gain	1.0000
X:2719706:G:GG	donor_gain	1.0000
X:2719707:T:A	donor_loss	1.0000
X:2719708:GAGTA:G	donor_loss	1.0000
X:2722622:CCTA:C	acceptor_loss	1.0000
X:2722623:CTA:C	acceptor_loss	1.0000
X:2722626:GGTA:G	acceptor_gain	1.0000
X:2722673:AGGT:A	donor_loss	1.0000

AlphaMissense

2412 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:2726308:C:A	A137D	1.000
Y:2726305:T:A	V136D	0.999
Y:2726320:C:A	A141D	0.999
Y:2726328:A:C	S144R	0.999
Y:2726330:C:A	S144R	0.999
Y:2726330:C:G	S144R	0.999
Y:2726296:C:A	A133D	0.998
Y:2726307:G:C	A137P	0.998
Y:2726314:C:A	A139D	0.998
Y:2726316:G:A	G140R	0.998
Y:2726316:G:C	G140R	0.998
Y:2726317:G:A	G140E	0.998
Y:2726323:T:A	I142N	0.998
Y:2726292:G:A	G132R	0.997
Y:2726292:G:C	G132R	0.997
Y:2726299:T:A	V134D	0.997
Y:2726319:G:C	A141P	0.997
Y:2726361:T:C	F155L	0.997
Y:2726363:C:A	F155L	0.997
Y:2726363:C:G	F155L	0.997
Y:2726311:T:A	V138E	0.996
Y:2726331:T:C	F145L	0.996
Y:2726333:C:A	F145L	0.996
Y:2726333:C:G	F145L	0.996
Y:2726338:C:A	A147D	0.996
Y:2726358:T:A	C154S	0.996
Y:2726359:G:C	C154S	0.996
Y:2726362:T:G	F155C	0.996
Y:2726287:T:A	I130N	0.995
Y:2726293:G:A	G132E	0.995

dbSNP variants (sampled 300 via entrez): RS1000037782 (X:2702263 C>G), RS1000332763 (X:2716426 G>A,T), RS1000448757 (X:2716259 T>C), RS1000565681 (X:2712268 A>G), RS1000641608 (X:2722885 G>A), RS1000692247 (X:2692693 C>T), RS1000698074 (X:2728178 G>A), RS1000740958 (X:2733144 C>G), RS1000751682 (X:2727953 G>A), RS1000866025 (X:2698156 T>A,C), RS1000892282 (X:2737651 C>A,T), RS1000928842 (X:2703636 G>GTGTGTGTT), RS1001055863 (X:2708682 TGGGAGAAG>T,TGGGAGAAGGGGAGAAG), RS1001110659 (X:2737357 T>C), RS1001207974 (X:2697452 A>G)

Disease associations

OMIM: gene MIM:313470, MIM:450000 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (2): primary ovarian failure (MONDO:0005387), autism (MONDO:0005260)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465269 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.82	Kd	1500	nM	CHEMBL5395918
5.75	Kd	1800	nM	CHEMBL5407716

PubChem BioAssay actives

2 with measured affinity, of 7 total; 2 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
2-[[(2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methoxy]propanedioic acid	1996048: Binding affinity to N-terminal biotin-tagged recombinant human CD99 extracellular domain (23 to 122 residues) expressed in Escherichia coli BL21(DE3) by surface plasmon resonance analysis	kd	1.5000	uM
(2R,3R,4S,5R)-5-(6-amino-2-pyridin-3-ylpurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol	1996048: Binding affinity to N-terminal biotin-tagged recombinant human CD99 extracellular domain (23 to 122 residues) expressed in Escherichia coli BL21(DE3) by surface plasmon resonance analysis	kd	1.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Doxorubicin	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Allergens	affects cotreatment, increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Vehicle Emissions	increases expression, affects cotreatment	1
Caffeine	decreases phosphorylation	1
Cannabidiol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression, affects expression	1
Diethylhexyl Phthalate	increases expression	1
Indomethacin	affects cotreatment, increases expression, affects expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5349175	Binding	Binding affinity to N-terminal biotin-tagged recombinant human CD99 extracellular domain (23 to 122 residues) expressed in Escherichia coli BL21(DE3) by surface plasmon resonance analysis	Design, synthesis and biological evaluation of Nucleosidic CD99 inhibitors that selectively reduce Ewing sarcoma viability. — Eur J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_QW72	TC-CD99-shRNA#1	Cancer cell line	Male
CVCL_QW73	TC-CD99-shRNA#2	Cancer cell line	Male
CVCL_QW75	BRZ-CD99-shRNA#1	Cancer cell line
CVCL_QW76	BRZ-CD99-shRNA#2	Cancer cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism