XG

Summary

XG (Xg glycoprotein (Xg blood group), HGNC:12806) is a protein-coding gene on chromosome Xp22.33, encoding Glycoprotein Xg (P55808).

This gene encodes the XG blood group antigen, and is located at the pseudoautosomal boundary on the short (p) arm of chromosome X. The three 5’ exons reside in the pseudoautosomal region and the remaining exons within the X-specific end. A truncated copy of this gene is found on the Y chromosome at the pseudoautosomal boundary. It is transcribed, but not expected to make a Y-chromosome specific gene product. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7499 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 59 total — 5 pathogenic
• MANE Select transcript: NM_001141919

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12806
Approved symbol	XG
Name	Xg glycoprotein (Xg blood group)
Location	Xp22.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000124343
Ensembl biotype	protein_coding
OMIM	300879
Entrez	7499

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000381174, ENST00000419513, ENST00000503018, ENST00000509484, ENST00000519244, ENST00000644266

RefSeq mRNA: 3 — MANE Select: NM_001141919 NM_001141919, NM_001141920, NM_175569

CCDS: CCDS14120, CCDS48073

Canonical transcript exons

ENST00000644266 — 11 exons

Exon	Start	End
ENSE00000846420	2782066	2782128
ENSE00000846421	2789644	2789706
ENSE00001311860	2811336	2811452
ENSE00001487705	2806701	2806745
ENSE00001689620	2808185	2808220
ENSE00001789719	2774716	2774739
ENSE00003550409	2770550	2770591
ENSE00003560990	2797310	2797360
ENSE00003609895	2794535	2794603
ENSE00003829651	2814364	2816500
ENSE00003902124	2752040	2752335

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 97.12.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2824 / max 313.4883, expressed in 247 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195379	2.5902	229
195381	0.3078	103
195382	0.1137	60
195378	0.0791	50
195383	0.0532	22
195380	0.0503	26
195377	0.0445	21
209585	0.0386	21
195385	0.0363	8
195386	0.0129	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.12	gold quality
tendon	UBERON:0000043	95.17	gold quality
skin of hip	UBERON:0001554	93.49	gold quality
skin of leg	UBERON:0001511	93.08	gold quality
zone of skin	UBERON:0000014	92.35	gold quality
skin of abdomen	UBERON:0001416	91.90	gold quality
upper leg skin	UBERON:0004262	90.38	gold quality
tendon of biceps brachii	UBERON:0008188	89.67	gold quality
gingival epithelium	UBERON:0001949	87.28	gold quality
layer of synovial tissue	UBERON:0007616	86.69	gold quality
secondary oocyte	CL:0000655	86.46	gold quality
gingiva	UBERON:0001828	86.12	gold quality
esophagus squamous epithelium	UBERON:0006920	85.63	gold quality
synovial joint	UBERON:0002217	84.65	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.46	gold quality
mammalian vulva	UBERON:0000997	83.99	gold quality
ascending aorta	UBERON:0001496	83.20	gold quality
thoracic aorta	UBERON:0001515	82.86	gold quality
esophagus mucosa	UBERON:0002469	81.57	gold quality
aorta	UBERON:0000947	80.93	gold quality
adipose tissue	UBERON:0001013	80.35	gold quality
tibial artery	UBERON:0007610	79.74	gold quality
popliteal artery	UBERON:0002250	79.71	gold quality
vagina	UBERON:0000996	79.48	gold quality
ectocervix	UBERON:0012249	78.60	gold quality
lower esophagus mucosa	UBERON:0035834	78.28	gold quality
descending thoracic aorta	UBERON:0002345	78.23	gold quality
buccal mucosa cell	CL:0002336	78.07	gold quality
right coronary artery	UBERON:0001625	77.92	gold quality
upper arm skin	UBERON:0004263	77.81	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting XG, 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-6867-5P	100.00	82.21	3464
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4420	99.82	70.08	1624

Literature-anchored findings (GeneRIF, showing 3)

• Gene frequency in France is similar to that reported in predominantly white populations. (PMID:18789743)
• The pseudoautosomal boundary on Xp22.33/Yp11.31 may harbor male-specific genetic variants for autism spectrum disorders. (PMID:24132906)
• The present findings identify the genetic basis of the erythroid-specific Xg(a)/CD99 blood group phenotypes and reveal the molecular background of their formation. (PMID:30061310)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Glycoprotein Xg — P55808 (reviewed: P55808)

Alternative names: Protein PBDX

All UniProt accessions (3): A0A2U3U020, E5RH28, P55808

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Tissue specificity. Expressed in erythroid tissues, including thymus, bone marrow and fetal liver, and in several nonerythroid tissues, such as heart, placenta, skeletal muscle, thyroid and trachea, as well as in skin fibroblasts. Expression is low or undetectable in other tissues.

Post-translational modifications. O-glycosylated.

Polymorphism. XG is responsible for the Xg blood group system.

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?
P55808-1	1	yes
P55808-2	2
P55808-3	3

RefSeq proteins (3): NP_001135391, NP_001135392, NP_780778 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022078	CD99L2	Family

Pfam: PF12301

UniProt features (11 total): topological domain 2, splice variant 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55808-F1	58.59	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_MYELOID_LEUKOCYTE_MIGRATION, 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, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_GRANULOCYTE_MIGRATION, GOBP_REGULATION_OF_CELLULAR_EXTRAVASATION, GOBP_T_CELL_MIGRATION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_HOMOTYPIC_CELL_CELL_ADHESION, GOBP_LYMPHOCYTE_MIGRATION, GOBP_REGULATION_OF_NEUTROPHIL_MIGRATION

GO Biological Process (3): homotypic cell-cell adhesion (GO:0034109), T cell extravasation (GO:0072683), positive regulation of neutrophil extravasation (GO:2000391)

GO Molecular Function (0):

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

78 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XG	CD99	P14209	860
XG	ARSD	P51689	767
XG	ARSF	P54793	765
XG	ARSL	P51690	750
XG	STS	P08842	649
XG	CD99L2	Q8TCZ2	348
XG	SMPDL3B	Q92485	235
XG	SLC43A1	O75387	224
XG	GYG2	O15488	220
XG	BIVM	Q86UB2	204
XG	GYPB	P06028	201
XG	BAAT	Q14032	199
XG	GATA1	P15976	185
XG	XK	P51811	182
XG	LANCL3	Q6ZV70	181

IntAct

0 interactions, top by confidence:

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1341989	GRCh37/hg19 Xp22.33(chrX:940688-2676609)x3	Pathogenic
1808677	GRCh37/hg19 Xp22.33(chrX:201705-2696762)x3	Pathogenic
686939	GRCh37/hg19 Xp22.33(chrX:168546-2696762)x3	Pathogenic
816242	GRCh37/hg19 Xp22.33(chrX:168546-3265521)x0	Pathogenic
988943	GRCh37/hg19 Xp22.33-22.32(chrX:60000-4857212)x1	Pathogenic

SpliceAI

1744 predictions. Top by Δscore:

Variant	Effect	Δscore
X:2782124:TGG:T	donor_gain	1.0000
X:2782129:G:GG	donor_gain	1.0000
X:2794602:AGGTA:A	donor_loss	1.0000
X:2794603:GGTA:G	donor_loss	1.0000
X:2794604:G:C	donor_loss	1.0000
X:2794605:T:G	donor_loss	1.0000
X:2811330:CTGCA:C	acceptor_loss	1.0000
X:2811331:TGCA:T	acceptor_loss	1.0000
X:2811332:GCAG:G	acceptor_loss	1.0000
X:2811333:CAG:C	acceptor_loss	1.0000
X:2811334:A:AG	acceptor_gain	1.0000
X:2811335:G:GG	acceptor_gain	1.0000
X:2811335:GGCA:G	acceptor_gain	1.0000
X:2811450:ATGG:A	donor_loss	1.0000
X:2811451:TGGT:T	donor_loss	1.0000
X:2811452:GGTA:G	donor_loss	1.0000
X:2811453:G:GG	donor_gain	1.0000
X:2811453:GT:G	donor_loss	1.0000
X:2811454:T:TC	donor_loss	1.0000
X:2752332:CGAG:C	donor_loss	0.9900
X:2752336:GT:G	donor_loss	0.9900
X:2752337:T:A	donor_loss	0.9900
X:2782125:GGA:G	donor_gain	0.9900
X:2782126:G:GT	donor_gain	0.9900
X:2789642:A:AG	acceptor_gain	0.9900
X:2789642:A:T	acceptor_loss	0.9900
X:2789643:G:GG	acceptor_gain	0.9900
X:2789643:GAT:G	acceptor_gain	0.9900
X:2789705:AGGTA:A	donor_loss	0.9900
X:2789706:GGTAA:G	donor_gain	0.9900

AlphaMissense

1270 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:2811366:T:A	I147N	0.992
X:2770568:T:C	L27S	0.990
X:2811369:T:A	V148E	0.987
X:2811384:T:A	V153E	0.984
X:2811363:C:A	P146H	0.983
X:2770561:T:C	F25L	0.981
X:2770563:T:A	F25L	0.981
X:2770563:T:G	F25L	0.981
X:2811363:C:G	P146R	0.981
X:2811381:T:A	V152E	0.981
X:2811378:T:A	V151E	0.979
X:2770562:T:G	F25C	0.978
X:2811390:T:G	L155R	0.977
X:2811395:G:A	G157R	0.977
X:2811395:G:C	G157R	0.977
X:2811375:T:A	V150E	0.976
X:2811396:G:A	G157E	0.976
X:2811390:T:C	L155P	0.970
X:2811357:T:A	V144E	0.968
X:2811401:G:C	A159P	0.965
X:2811402:C:A	A159E	0.965
X:2770562:T:C	F25S	0.963
X:2770568:T:G	L27W	0.959
X:2770576:G:C	A30P	0.958
X:2811363:C:T	P146L	0.958
X:2811387:C:A	T154K	0.958
X:2811390:T:A	L155Q	0.957
X:2811354:T:A	I143N	0.954
X:2770580:T:A	L31H	0.952
X:2811387:C:G	T154R	0.952

dbSNP variants (sampled 300 via entrez): RS1000046962 (X:2779376 A>G), RS1000304912 (X:2800326 C>G), RS1000323278 (X:2789289 A>G,T), RS1000376513 (X:2801131 A>G), RS1000409160 (X:2800644 C>T), RS1000481837 (X:2754149 A>C), RS1000515877 (X:2759056 C>T), RS1000572700 (X:2764956 G>A), RS1000579569 (X:2759511 T>C), RS1000763021 (X:2753970 T>C,G), RS1000848678 (X:2775322 G>A,T), RS1001029901 (X:2809901 C>G), RS1001053807 (X:2780992 T>TG), RS1001120027 (X:2774720 C>A,T), RS1001166143 (X:2769130 G>A)

Disease associations

OMIM: gene MIM:300879 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
incobotulinumtoxinA	increases expression	1
Benzo(a)pyrene	decreases expression	1
Dexamethasone	increases expression	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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