XKR3

Summary

XKR3 (XK related 3, HGNC:28778) is a protein-coding gene on chromosome 22q11.1, encoding XK-related protein 3 (Q5GH77).

XKRX (MIM 300684) and XKR3 are homologs of the Kell blood group precursor XK (MIM 314850), which is a putative membrane transporter and a component of the XK/Kell complex of the Kell blood group system (Calenda et al., 2006 [PubMed 16431037]).

Source: NCBI Gene 150165 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_001386955

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28778
Approved symbol	XKR3
Name	XK related 3
Location	22q11.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC57211, XTES
Ensembl gene	ENSG00000172967
Ensembl biotype	protein_coding
OMIM	611674
Entrez	150165

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000331428, ENST00000684488

RefSeq mRNA: 5 — MANE Select: NM_001386955 NM_001318251, NM_001386955, NM_001386956, NM_001386957, NM_175878

CCDS: CCDS42975

Canonical transcript exons

ENST00000684488 — 4 exons

Exon	Start	End
ENSE00001196508	16799771	16800024
ENSE00001303813	16807739	16808083
ENSE00003916355	16783480	16784409
ENSE00003921769	16825291	16825411

Expression profiles

Bgee: expression breadth broad, 18 present calls, max score 80.17.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.17	gold quality
testis	UBERON:0000473	68.27	gold quality
left testis	UBERON:0004533	67.84	gold quality
right testis	UBERON:0004534	67.43	gold quality
blood	UBERON:0000178	50.82	gold quality
monocyte	CL:0000576	44.07	silver quality
leukocyte	CL:0000738	43.11	silver quality
left adrenal gland cortex	UBERON:0035825	40.49	gold quality
right lung	UBERON:0002167	39.53	silver quality
spleen	UBERON:0002106	38.51	silver quality
bone marrow cell	CL:0002092	38.25	gold quality
left adrenal gland	UBERON:0001234	38.12	silver quality
bone marrow	UBERON:0002371	37.51	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
granulocyte	CL:0000094	35.72	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
adrenal gland	UBERON:0002369	35.22	silver quality
right adrenal gland	UBERON:0001233	34.78	gold quality
right adrenal gland cortex	UBERON:0035827	34.27	gold quality
lymph node	UBERON:0000029	34.17	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
duodenum	UBERON:0002114	32.74	gold quality
superior frontal gyrus	UBERON:0002661	32.65	gold quality
vermiform appendix	UBERON:0001154	32.34	gold quality
muscle tissue	UBERON:0002385	32.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
endometrium	UBERON:0001295	32.12	gold quality
calcaneal tendon	UBERON:0003701	32.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

16 targeting XKR3, 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-3646	100.00	73.56	5283
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-219A-2-3P	98.62	68.78	797
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-3622A-5P	97.43	67.11	356
HSA-MIR-2114-3P	95.45	66.11	579
HSA-MIR-6823-3P	95.45	66.14	704

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

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	xkrx	ENSDARG00000044011

Paralogs (2): XK (ENSG00000047597), XKRX (ENSG00000182489)

Protein

Protein identifiers

XK-related protein 3 — Q5GH77 (reviewed: Q5GH77)

Alternative names: X Kell blood group-related 3, XTES

All UniProt accessions (1): Q5GH77

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Tissue specificity. Expressed predominantly, if not exclusively, in testis.

Similarity. Belongs to the XK family.

RefSeq proteins (5): NP_001305180, NP_001373884, NP_001373885, NP_001373886, NP_787074 (=MANE)

Domains & families (InterPro)

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

Pfam: PF09815

UniProt features (15 total): transmembrane region 10, sequence variant 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5GH77-F1	77.14	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 9 (showing top): GABRIELY_MIR21_TARGETS, ZIM3_TARGET_GENES, ZNF507_TARGET_GENES, MIR3646, MIR568, MIR4768_3P, MIR219A_2_3P, PULVER_FOREY_CELLCYCLE_PEAKING_LG1, chr22q11

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

570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XKR3	KEL	P23276	887
XKR3	NUP214	P35658	581
XKR3	ARSD	P51689	570
XKR3	ZNF335	Q9H4Z2	512
XKR3	KRTAP10-1	P60331	431
XKR3	FRG2B	Q96QU4	420
XKR3	CECR2	Q9BXF3	416
XKR3	CCDC89	Q8N998	410
XKR3	MPP4	Q96JB8	400
XKR3	TXLNG	Q9NUQ3	398
XKR3	CCT8L2	Q96SF2	396
XKR3	ADA2	Q9NZK5	370
XKR3	KRTAP4-3	Q9BYR4	369
XKR3	SLC25A18	Q9H1K4	366
XKR3	KIAA1671	Q9BY89	366

IntAct

0 interactions, top by confidence:

BioGRID (3): XKR3 (Two-hybrid), XKR3 (Two-hybrid), XKR3 (Two-hybrid)

ESM2 similar proteins: A0A494BZU4, A0A7H0DND7, A0JNG0, A2T345, A4IIV4, C4QM85, E7F594, G5EDX4, O02051, O45306, P0DP42, P0DST5, P0DST6, P21061, P24763, P34362, P34363, P53053, Q09282, Q0II41, Q10907, Q11071, Q11085, Q13571, Q20249, Q297K8, Q2KHT4, Q2KJA5, Q32KQ5, Q5DC12, Q5GH77, Q5PQM0, Q5RD28, Q5REZ0, Q5TAH2, Q61168, Q6AXT9, Q6GV27, Q6GV28, Q7K1V5

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1081 predictions. Top by Δscore:

Variant	Effect	Δscore
22:16784405:CAATG:C	acceptor_gain	1.0000
22:16784380:C:CC	acceptor_gain	0.9900
22:16784408:TG:T	acceptor_gain	0.9900
22:16784410:C:CC	acceptor_gain	0.9900
22:16799918:C:CA	donor_gain	0.9900
22:16808131:T:TC	acceptor_gain	0.9900
22:16784406:AATG:A	acceptor_gain	0.9800
22:16784408:TGCT:T	acceptor_loss	0.9800
22:16784410:C:CG	acceptor_loss	0.9800
22:16800835:A:AC	donor_gain	0.9800
22:16800836:C:CC	donor_gain	0.9800
22:16808127:A:T	acceptor_gain	0.9800
22:16808128:G:GC	acceptor_gain	0.9800
22:16808137:T:C	acceptor_gain	0.9800
22:16784425:A:C	acceptor_gain	0.9700
22:16808126:CAG:C	acceptor_gain	0.9700
22:16808128:G:C	acceptor_gain	0.9700
22:16784407:ATG:A	acceptor_gain	0.9600
22:16784413:T:TC	acceptor_gain	0.9600
22:16821601:TTTTA:T	donor_loss	0.9600
22:16821602:TTTAC:T	donor_loss	0.9600
22:16821603:TTAC:T	donor_loss	0.9600
22:16821604:TA:T	donor_loss	0.9600
22:16784169:A:T	acceptor_gain	0.9500
22:16794152:T:TA	donor_gain	0.9500
22:16799867:A:AC	donor_gain	0.9500
22:16799868:C:CC	donor_gain	0.9500
22:16808117:A:T	acceptor_gain	0.9500
22:16808137:T:TC	acceptor_gain	0.9500
22:16808131:T:C	acceptor_gain	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000107407 (22:16789124 T>C), RS1000117393 (22:16807164 T>C), RS1000142500 (22:16811828 G>A), RS1000349432 (22:16817674 C>G), RS1000427674 (22:16824046 T>C), RS1000460118 (22:16823801 A>G), RS1000468139 (22:16789779 C>T), RS1000659002 (22:16817990 A>G), RS1000721184 (22:16805786 A>C), RS1000859585 (22:16822554 A>T), RS1001124276 (22:16810422 T>G), RS1001509373 (22:16798114 AGGTTGCAGTG>A), RS1001602755 (22:16797857 T>C), RS1001671775 (22:16804366 CA>C), RS1001773862 (22:16816240 T>C)

Disease associations

OMIM: gene MIM:611674 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007335_36	Age at first sexual intercourse	2.000000e-07
GCST010736_12	Urinary albumin-to-creatinine ratio	7.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009749	age at first sexual intercourse measurement
EFO:0007778	urinary albumin to creatinine ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Acetaminophen	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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