CD101

Summary

CD101 (CD101 molecule, HGNC:5949) is a protein-coding gene on chromosome 1p13.1, encoding Immunoglobulin superfamily member 2 (Q93033). Plays a role as inhibitor of T-cells proliferation induced by CD3.

Predicted to enable hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides. Predicted to be involved in cell surface receptor signaling pathway. Predicted to act upstream of or within positive regulation of myeloid leukocyte differentiation. Located in extracellular exosome.

Source: NCBI Gene 9398 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 157 total — 1 pathogenic
• MANE Select transcript: NM_001256106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5949
Approved symbol	CD101
Name	CD101 molecule
Location	1p13.1
Locus type	gene with protein product
Status	Approved
Aliases	V7
Ensembl gene	ENSG00000134256
Ensembl biotype	protein_coding
OMIM	604516
Entrez	9398

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000256652, ENST00000369470, ENST00000460180, ENST00000467588, ENST00000682167, ENST00000893743, ENST00000893744, ENST00000893745, ENST00000893746, ENST00000964338

RefSeq mRNA: 4 — MANE Select: NM_001256106 NM_001256106, NM_001256109, NM_001256111, NM_004258

CCDS: CCDS891

Canonical transcript exons

ENST00000682167 — 10 exons

Exon	Start	End
ENSE00000785014	117011550	117011966
ENSE00000785015	117013406	117013792
ENSE00000785016	117017090	117017473
ENSE00000785017	117018156	117018560
ENSE00000785018	117021573	117021983
ENSE00000785019	117025509	117025904
ENSE00001020950	117009850	117010230
ENSE00003578009	117033860	117034134
ENSE00003916943	117036168	117036552
ENSE00003920927	117001760	117001860

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 93.18.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3235 / max 199.2100, expressed in 195 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4861	1.1835	190
201632	0.1400	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	93.18	gold quality
granulocyte	CL:0000094	93.08	gold quality
mononuclear cell	CL:0000842	92.47	gold quality
leukocyte	CL:0000738	92.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.91	gold quality
right lung	UBERON:0002167	79.85	gold quality
mucosa of transverse colon	UBERON:0004991	79.10	gold quality
bone marrow cell	CL:0002092	78.56	gold quality
ventricular zone	UBERON:0003053	78.16	gold quality
bone marrow	UBERON:0002371	77.94	gold quality
upper lobe of left lung	UBERON:0008952	77.64	gold quality
blood	UBERON:0000178	76.76	gold quality
cortical plate	UBERON:0005343	76.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.93	gold quality
rectum	UBERON:0001052	75.88	gold quality
spleen	UBERON:0002106	75.65	gold quality
lower esophagus mucosa	UBERON:0035834	75.65	gold quality
upper lobe of lung	UBERON:0008948	75.47	gold quality
ganglionic eminence	UBERON:0004023	73.65	gold quality
small intestine	UBERON:0002108	72.76	gold quality
transverse colon	UBERON:0001157	71.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	71.56	gold quality
cingulate cortex	UBERON:0003027	71.24	gold quality
anterior cingulate cortex	UBERON:0009835	71.09	gold quality
vermiform appendix	UBERON:0001154	71.07	gold quality
right frontal lobe	UBERON:0002810	70.57	gold quality
smooth muscle tissue	UBERON:0001135	70.28	gold quality
body of pancreas	UBERON:0001150	69.98	gold quality
right adrenal gland	UBERON:0001233	69.90	gold quality
right adrenal gland cortex	UBERON:0035827	69.57	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXP3

miRNA regulators (miRDB)

16 targeting CD101, 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-1193	100.00	65.93	529
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-6890-5P	92.89	65.83	442

Literature-anchored findings (GeneRIF, showing 8)

• Results suggest a possible role for CD101 expression and function in the control of certain manifestations of rheumatoid arthritis pathology. (PMID:21159825)
• Single Nucleotide Polymorphism in CD101 gene may be associated with pancreatic cancer. (PMID:21467233)
• Low expression of CD39(+) /CD45RA(+) on regulatory T cells (Treg ) cells in type 1 diabetic children in contrast to high expression of CD101(+) /CD129(+) on Treg cells in children with coeliac disease. (PMID:25421756)
• In patients with intestinal bowel disease, a reduced CD101 expression on peripheral and intestinal monocytes and CD4-positive Tcells correlated with enhanced IL-17 production and disease activity. (PMID:26813346)
• Study shows nucleotide substitutions in CD101, the human homolog of a diabetes susceptibility gene in non-obese diabetic mouse, in patients with type 1 diabetes. The results raise the possibility that CD101 is a susceptibility gene for type 1 diabetes. (PMID:27888582)
• variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1 (PMID:29108000)
• Brief Report: Bacterial Vaginosis and Risk of HIV Infection in the Context of CD101 Gene Variation. (PMID:32976203)
• CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions. (PMID:34195685)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd101	ENSMUSG00000086564
rattus_norvegicus	Cd101	ENSRNOG00000037190

Paralogs (5): PTGFRN (ENSG00000134247), IGSF3 (ENSG00000143061), IGSF8 (ENSG00000162729), VSTM4 (ENSG00000165633), VSTM2A (ENSG00000170419)

Protein

Protein identifiers

Immunoglobulin superfamily member 2 — Q93033 (reviewed: Q93033)

Alternative names: Cell surface glycoprotein V7, Glu-Trp-Ile EWI motif-containing protein 101

All UniProt accessions (1): Q93033

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as inhibitor of T-cells proliferation induced by CD3. Inhibits expression of IL2RA on activated T-cells and secretion of IL2. Inhibits tyrosine kinases that are required for IL2 production and cellular proliferation. Inhibits phospholipase C-gamma-1/PLCG1 phosphorylation and subsequent CD3-induced changes in intracellular free calcium. Prevents nuclear translocation of nuclear factor of activated T-cell to the nucleus. Plays a role in the inhibition of T-cell proliferation via IL10 secretion by cutaneous dendritic cells. May be a marker of CD4(+) CD56(+) leukemic tumor cells.

Subcellular location. Membrane.

Tissue specificity. Expressed in lung, thymus and small intestine. Detected in cutaneous dendritic cells, activated T-cells, monocytes and granulocytes as well as with epithelial cells with dendritic morphology. Expressed in some leukemic cells, the CD4(+) CD56(+) blastic tumor cells, as well as in Langerhans cells from LCH (Langerhans cell histiocytosis) patients.

Post-translational modifications. N-glycosylated.

RefSeq proteins (4): NP_001243035, NP_001243038, NP_001243040, NP_004249 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002195	Dihydroorotase_CS	Conserved_site
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051102	IgSF_V-set/TM_domain	Family

Pfam: PF07686

UniProt features (38 total): sequence variant 11, domain 7, disulfide bond 7, sequence conflict 5, glycosylation site 2, topological domain 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93033-F1	81.76	0.38

Functional residue map

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

Disulfide bonds (7): 43–121, 168–249, 304–377, 434–511, 562–640, 697–778, 834–909

Glycosylation sites (2): 44, 322

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-202433	Generation of second messenger molecules

MSigDB gene sets: 112 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, PEREZ_TP63_TARGETS, GOBP_T_CELL_HOMEOSTASIS, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_HEMOPOIESIS, MODULE_75, GOBP_RESPONSE_TO_INSULIN, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, MODULE_99, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (2): positive regulation of myeloid leukocyte differentiation (GO:0002763), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (1): hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides (GO:0016812)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TCR signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
myeloid leukocyte differentiation	1
regulation of myeloid leukocyte differentiation	1
positive regulation of myeloid cell differentiation	1
positive regulation of leukocyte differentiation	1
signal transduction	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
membrane	1
cell periphery	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD101	CD53	P19397	719
CD101	CD9	P21926	616
CD101	HAVCR2	Q8TDQ0	602
CD101	CD3G	P09693	596
CD101	CD58	P19256	585
CD101	CD81	P18582	546
CD101	CD2	P06729	537
CD101	ITGAE	P38570	510
CD101	KRTAP9-8	Q9BYQ0	487
CD101	AKAP5	P24588	482
CD101	CD8A	P01732	446
CD101	ITGA1	P56199	445
CD101	CD52	P31358	434
CD101	CD38	P28907	424
CD101	CD69	Q07108	421

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CD101	SRSF5	psi-mi:“MI:0915”(physical association)	0.000
CD101	SH3GL3	psi-mi:“MI:0915”(physical association)	0.000
CD101	ST13	psi-mi:“MI:0915”(physical association)	0.000
CD101	PUF60	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): SRSF5 (Two-hybrid), SH3GL3 (Two-hybrid), ST13 (Two-hybrid), CD101 (Affinity Capture-RNA), CD101 (Affinity Capture-MS), STK10 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A140LHF2, A0JPB1, A2AJ76, A7LCJ3, A8E0Y8, E7FF10, O00241, O60500, P01874, P03988, P04221, P0DOX2, P0DOX3, P0DOX4, P0DOX6, P0DP72, P32507, P35590, P43121, P50895, Q06805, Q06806, Q148M6, Q15109, Q5TFQ8, Q5U5A3, Q5XI43, Q62230, Q62786, Q8HW98, Q8NDA2, Q8R2Y2, Q92154, Q923P0, Q93033, Q95KI3, Q96MS0, Q9BRK3, Q9BZZ2, Q9DBV4

Diamond homologs: A0JPB1, A8E0Y8, O75054, Q5U5A3, Q6ZQA6, Q8R366, Q93033, Q969P0, Q62786, Q9WV91

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	121
Likely benign	15
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57384	GRCh38/hg38 1p13.1-12(chr1:116679122-119290029)x1	Pathogenic

SpliceAI

1726 predictions. Top by Δscore:

Variant	Effect	Δscore
1:117001859:GA:G	donor_gain	1.0000
1:117001861:G:GG	donor_gain	1.0000
1:117018558:CAGGT:C	donor_loss	1.0000
1:117018559:AGGT:A	donor_loss	1.0000
1:117018560:GGT:G	donor_loss	1.0000
1:117025653:G:GT	donor_gain	1.0000
1:117009841:A:AG	acceptor_gain	0.9900
1:117009847:A:AG	acceptor_gain	0.9900
1:117009848:A:G	acceptor_gain	0.9900
1:117010201:G:GT	donor_gain	0.9900
1:117011963:GCAG:G	donor_gain	0.9900
1:117011967:G:GA	donor_loss	0.9900
1:117011968:T:G	donor_loss	0.9900
1:117013404:A:AG	acceptor_gain	0.9900
1:117013405:G:GG	acceptor_gain	0.9900
1:117013405:GT:G	acceptor_gain	0.9900
1:117013619:TTTCA:T	donor_gain	0.9900
1:117017073:T:G	acceptor_gain	0.9900
1:117017074:A:AG	acceptor_gain	0.9900
1:117017074:AATCT:A	acceptor_gain	0.9900
1:117017078:T:TA	acceptor_gain	0.9900
1:117017081:A:AG	acceptor_gain	0.9900
1:117017082:A:G	acceptor_gain	0.9900
1:117018154:A:AG	acceptor_gain	0.9900
1:117018155:G:GG	acceptor_gain	0.9900
1:117018155:GA:G	acceptor_gain	0.9900
1:117018557:CCAG:C	donor_gain	0.9900
1:117018558:CAG:C	donor_gain	0.9900
1:117018559:AG:A	donor_gain	0.9900
1:117018560:GG:G	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015200 (1:117025192 G>A), RS1000267198 (1:117000294 C>G,T), RS1000499616 (1:117030450 A>G), RS1000572637 (1:117019323 C>T), RS1000713471 (1:117023846 G>A), RS1000721918 (1:117016179 C>T), RS1000739502 (1:117013027 G>C), RS1000922554 (1:117033341 G>T), RS1000933181 (1:117010133 A>C,G), RS1000998731 (1:117019651 A>G), RS1001047391 (1:117027050 C>T), RS1001289401 (1:117033012 G>A), RS1001335330 (1:117031230 T>C), RS1001366293 (1:117031575 T>G), RS1001427958 (1:117011011 T>C)

Disease associations

OMIM: gene MIM:604516 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002398_491	Neutrophil count	5.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Cisplatin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Tretinoin	increases expression	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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