XKRX

Summary

XKRX (XK related X-linked, HGNC:29845) is a protein-coding gene on chromosome Xq22.1, encoding XK-related protein 2 (Q6PP77).

This gene encodes a protein that is related to a component of the XK/Kell complex of the Kell blood group system. The encoded protein includes several transmembrane domains, is known to be exposed to the cell surface, and may function as a membrane transporter.

Source: NCBI Gene 402415 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_212559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29845
Approved symbol	XKRX
Name	XK related X-linked
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	XPLAC, XKR2
Ensembl gene	ENSG00000182489
Ensembl biotype	protein_coding
OMIM	300684
Entrez	402415

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000372956, ENST00000468904

RefSeq mRNA: 1 — MANE Select: NM_212559 NM_212559

CCDS: CCDS14476

Canonical transcript exons

ENST00000372956 — 3 exons

Exon	Start	End
ENSE00001316227	100922793	100923061
ENSE00001328213	100927970	100928917
ENSE00001459147	100913445	100915083

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 82.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1346 / max 13.5507, expressed in 59 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199937	0.1346	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.67	gold quality
skin of leg	UBERON:0001511	77.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.61	silver quality
zone of skin	UBERON:0000014	75.33	gold quality
skin of abdomen	UBERON:0001416	75.05	gold quality
lower esophagus mucosa	UBERON:0035834	74.29	gold quality
esophagus squamous epithelium	UBERON:0006920	68.76	silver quality
gingival epithelium	UBERON:0001949	68.62	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	67.09	gold quality
amniotic fluid	UBERON:0000173	66.50	silver quality
left ventricle myocardium	UBERON:0006566	66.45	gold quality
esophagus mucosa	UBERON:0002469	66.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.13	gold quality
gingiva	UBERON:0001828	65.29	silver quality
upper leg skin	UBERON:0004262	64.95	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	63.24	gold quality
palpebral conjunctiva	UBERON:0001812	62.80	silver quality
epithelium of nasopharynx	UBERON:0001951	62.53	silver quality
upper lobe of left lung	UBERON:0008952	62.14	gold quality
mammalian vulva	UBERON:0000997	62.02	silver quality
tonsil	UBERON:0002372	61.77	gold quality
upper lobe of lung	UBERON:0008948	61.65	gold quality
lymph node	UBERON:0000029	60.63	gold quality
bone marrow cell	CL:0002092	59.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	59.60	gold quality
mucosa of transverse colon	UBERON:0004991	59.02	gold quality
vermiform appendix	UBERON:0001154	58.87	gold quality
vagina	UBERON:0000996	58.79	gold quality
placenta	UBERON:0001987	58.22	gold quality
rectum	UBERON:0001052	58.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting XKRX, 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-4668-3P	100.00	68.74	2635
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-657	99.48	66.02	848
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-125A-5P	99.36	70.59	1640

Literature-anchored findings (GeneRIF, showing 1)

• XPLAC is expressed mostly in placenta and adrenal gland while XTES is exclusively expressed in primate testis (PMID:16431037)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	xkrx	ENSDARG00000044011
mus_musculus	Xkrx	ENSMUSG00000031258
rattus_norvegicus	Xkrx	ENSRNOG00000089589

Paralogs (2): XK (ENSG00000047597), XKR3 (ENSG00000172967)

Protein

Protein identifiers

XK-related protein 2 — Q6PP77 (reviewed: Q6PP77)

Alternative names: Membrane protein XPLAC, X Kell blood group-related, X-linked

All UniProt accessions (2): Q6PP77, C9JYI8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Tissue specificity. Expressed predominantly in the placenta, in syncytiotrophoblasts. Moderate levels in the adrenal gland, low levels in the trachea and very low levels in the bone marrow.

Similarity. Belongs to the XK family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6PP77-1	1	yes
Q6PP77-2	2

RefSeq proteins (1): NP_997724* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018629	XK-rel	Family
IPR051773	XK-related_adapter	Family

Pfam: PF09815

UniProt features (13 total): transmembrane region 10, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PP77-F1	80.93	0.45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): TGACATY_UNKNOWN, HAND1E47_01, PIT1_Q6, FOXO4_02, TGGAAA_NFAT_Q4_01, GAVIN_FOXP3_TARGETS_CLUSTER_P7, PAX6_01, RP58_01, chrXq22, GSE13522_WT_VS_IFNAR_KO_SKING_T_CRUZI_Y_STRAIN_INF_DN, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_IFNAR_KO_UP, GSE13522_WT_VS_IFNAR_KO_SKIN_UP, GSE14699_NAIVE_VS_DELETIONAL_TOLERANCE_CD8_TCELL_UP, GSE14699_NAIVE_VS_ACT_CD8_TCELL_DN, GSE13946_CTRL_VS_DSS_COLITIS_GD_TCELL_FROM_COLON_DN

GO Biological Process (0):

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
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

620 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XKRX	KEL	P23276	865
XKRX	IGFL4	Q6B9Z1	472
XKRX	TMEM234	Q8WY98	455
XKRX	XKR9	Q5GH70	436
XKRX	TCP11L2	Q8N4U5	430
XKRX	FAM171B	Q6P995	419
XKRX	CDYL2	Q8N8U2	406
XKRX	HSFY1	Q96LI6	397
XKRX	MAB21L4	Q08AI8	392
XKRX	RPP30	P78346	387
XKRX	RTL6	Q6ICC9	373
XKRX	KRTAP3-1	Q9BYR8	366
XKRX	DAZL	Q92904	353
XKRX	TMEM64	Q6YI46	352
XKRX	SPRR4	Q96PI1	350

IntAct

4 interactions, top by confidence:

A	B	Type	Score
XKRX	FAM234B	psi-mi:“MI:0914”(association)	0.530
MYC		psi-mi:“MI:0914”(association)	0.350

BioGRID (17): VPS13A (Affinity Capture-MS), UBXN7 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), SPRTN (Affinity Capture-MS), ITFG3 (Affinity Capture-MS), KIAA1467 (Affinity Capture-MS), TRAFD1 (Affinity Capture-MS), FAM175B (Affinity Capture-MS), XKRX (Synthetic Lethality), XKRX (Synthetic Lethality), CD320 (Affinity Capture-MS), VPS13A (Affinity Capture-MS), TRAFD1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), ITFG3 (Affinity Capture-MS)

ESM2 similar proteins: A0A452G813, A0A8V0ZB02, A1L3G9, A2AWR3, A9LIW2, B6HTR9, D3ZNF5, F4I248, F4JCY2, O35379, O57428, O94886, O94911, P08983, Q059Y8, Q06538, Q09427, Q09428, Q09429, Q17JQ7, Q3KTM2, Q3TWI9, Q4R7U0, Q4V8U5, Q5GH22, Q5GH60, Q5GH68, Q5R826, Q5R9A7, Q5T3F8, Q5YCC5, Q6NP91, Q6PP77, Q6UR05, Q7Q5R7, Q7Z3F1, Q7Z402, Q8C428, Q8CBX0, Q8CG09

Diamond homologs: O14609, P51811, Q49LS5, Q5GH22, Q5GH60, Q5GH61, Q5GH68, Q5GH77, Q6PP77, Q9QXY7, Q49LS9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

662 predictions. Top by Δscore:

Variant	Effect	Δscore
X:100915081:CAA:C	acceptor_gain	1.0000
X:100915046:A:C	acceptor_gain	0.9900
X:100915061:C:CT	acceptor_gain	0.9900
X:100915079:CACAA:C	acceptor_gain	0.9900
X:100915080:ACAA:A	acceptor_gain	0.9900
X:100915081:CAAC:C	acceptor_gain	0.9900
X:100915082:AA:A	acceptor_gain	0.9900
X:100915083:ACTG:A	acceptor_loss	0.9900
X:100915084:C:CC	acceptor_gain	0.9900
X:100915084:CT:C	acceptor_loss	0.9900
X:100915085:T:G	acceptor_loss	0.9900
X:100915087:T:C	acceptor_gain	0.9900
X:100915087:T:TC	acceptor_gain	0.9900
X:100915094:C:CT	acceptor_gain	0.9900
X:100915095:A:T	acceptor_gain	0.9900
X:100923059:CAT:C	acceptor_gain	0.9900
X:100915045:C:CT	acceptor_gain	0.9800
X:100915045:C:T	acceptor_gain	0.9800
X:100915062:A:T	acceptor_gain	0.9800
X:100915086:G:C	acceptor_gain	0.9800
X:100922887:A:AC	donor_gain	0.9800
X:100922888:C:CC	donor_gain	0.9800
X:100923062:C:CC	acceptor_gain	0.9800
X:100928661:T:TA	donor_gain	0.9800
X:100915043:CCCA:C	acceptor_gain	0.9700
X:100915044:CCA:C	acceptor_gain	0.9700
X:100922789:TCACC:T	donor_loss	0.9700
X:100922791:ACCTC:A	donor_loss	0.9700
X:100922792:CCTC:C	donor_loss	0.9700
X:100922957:T:TA	donor_gain	0.9700

AlphaMissense

2936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:100914835:A:G	W285R	0.999
X:100914835:A:T	W285R	0.999
X:100914952:A:G	W246R	0.999
X:100914952:A:T	W246R	0.999
X:100915044:C:T	G215E	0.999
X:100915045:C:A	G215W	0.999
X:100915045:C:G	G215R	0.999
X:100915045:C:T	G215R	0.999
X:100922866:G:C	F177L	0.999
X:100922866:G:T	F177L	0.999
X:100922868:A:G	F177L	0.999
X:100922903:C:G	R165P	0.999
X:100922984:C:G	R138P	0.999
X:100914485:G:C	F401L	0.998
X:100914485:G:T	F401L	0.998
X:100914487:A:G	F401L	0.998
X:100914608:A:C	N360K	0.998
X:100914608:A:T	N360K	0.998
X:100914687:A:G	L334S	0.998
X:100923060:A:G	C113R	0.998
X:100927979:G:C	P109R	0.998
X:100927983:C:G	G108R	0.998
X:100927983:C:T	G108R	0.998
X:100928036:C:A	R90I	0.998
X:100928051:A:G	L85P	0.998
X:100914693:A:G	L332S	0.997
X:100914948:C:G	R247P	0.997
X:100922846:A:G	L184P	0.997
X:100922915:A:G	L161P	0.997
X:100922921:C:G	R159P	0.997

dbSNP variants (sampled 300 via entrez): RS1000071282 (X:100907201 T>A), RS1000125753 (X:100908765 T>C), RS1000130675 (X:100892826 G>A), RS1000136736 (X:100897303 G>A), RS1000243631 (X:100917690 G>A,T), RS1000435732 (X:100945729 C>T), RS1000450889 (X:100914805 T>C), RS1000455249 (X:100901033 G>A,C), RS1000681353 (X:100890604 C>T), RS1000718129 (X:100956847 C>A,T), RS1000732728 (X:100911295 T>C), RS1000765905 (X:100948214 A>G), RS1000820173 (X:100947562 C>A), RS1000858385 (X:100923816 GCTTTTT>G), RS1000871306 (X:100924400 G>A)

Disease associations

OMIM: gene MIM:300684 | 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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
hydroquinone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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