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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
XK
X-linked Kx blood group antigen, Kell and VPS13A binding protein
Chromosome X Β· Xp21.1
NCBI Gene: 7504Ensembl: ENSG00000047597.7HGNC: HGNC:12811UniProt: P51811
41PubMed Papers
21Diseases
0Drugs
14Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingprotein-macromolecule adaptor activityendoplasmic reticulum membraneplasma membraneMcLeod neuroacanthocytosis syndromegenetic disorderisolated asymptomatic elevation of creatine phosphokinaseElevated circulating creatine kinase concentration
✦AI Summary

The XK gene encodes an X-linked membrane protein that serves as a critical adaptor for intracellular protein interactions and membrane organization. The protein functions primarily by recruiting the lipid transfer protein VPS13A from lipid droplets to the endoplasmic reticulum (ER) membrane, facilitating lipid transport and membrane homeostasis. XK localizes to both the endoplasmic reticulum membrane and plasma membrane, where it exhibits protein-macromolecule adaptor activity through direct protein binding interactions. The gene is most notably associated with McLeod syndrome, a rare X-linked disorder characterized by neurological and hematological abnormalities. Additionally, XK mutations are linked to XK aprosencephaly syndrome, a severe developmental disorder featuring absent forebrain structures, preaxial limb defects, and ambiguous genitalia 12. This syndrome may involve DNA repair defects, as evidenced by increased chromosome X in affected individuals 2. The protein's role as a membrane adaptor suggests it is essential for proper cellular membrane dynamics and protein trafficking, with its dysfunction leading to significant developmental and physiological consequences. However, detailed mechanistic studies of XK protein function remain limited in the current literature.

Sources cited
1
Documents a case of XK aprosencephaly syndrome with characteristic features including aprosencephaly, preaxial limb defect and ambiguous genitalia
PMID: 9571288
2
Provides additional characterization of XK aprosencephaly syndrome and suggests possible DNA repair defects based on increased chromosome breakage
PMID: 16208689
⚠Limited data available β€” This gene has 2 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
McLeod neuroacanthocytosis syndromeOpen Targets
0.80Strong
genetic disorderOpen Targets
0.41Moderate
isolated asymptomatic elevation of creatine phosphokinaseOpen Targets
0.27Weak
Elevated circulating creatine kinase concentrationOpen Targets
0.26Weak
glioblastoma multiformeOpen Targets
0.09Suggestive
Blackfan-Diamond anemiaOpen Targets
0.09Suggestive
in situ carcinomaOpen Targets
0.08Suggestive
infectionOpen Targets
0.07Suggestive
influenzaOpen Targets
0.07Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.07Suggestive
acute lymphoblastic leukemiaOpen Targets
0.07Suggestive
inosine triphosphatase deficiencyOpen Targets
0.07Suggestive
Huntington diseaseOpen Targets
0.07Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.07Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.07Suggestive
age-related macular degenerationOpen Targets
0.06Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.06Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
benign prostatic hyperplasiaOpen Targets
0.06Suggestive
McLeod syndromeUniProt
Pathogenic Variants14
NM_021083.4(XK):c.856_860del (p.Leu286fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 286
NM_021083.4(XK):c.664C>T (p.Arg222Ter)Pathogenic
XK-related neurodegenerative disease|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 222
NM_021083.4(XK):c.719dup (p.Ile241fs)Pathogenic
XK-related neurodegenerative disease
β˜…β˜†β˜†β˜†2025β†’ Residue 241
NM_021083.4(XK):c.274C>T (p.Gln92Ter)Pathogenic
XK-related disorder|not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 92
NM_021083.4(XK):c.397C>T (p.Arg133Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 133
NM_021083.4(XK):c.1015A>T (p.Lys339Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2017β†’ Residue 339
NM_021083.4(XK):c.938_951del (p.Asn313fs)Pathogenic
XK-related neurodegenerative disease
β˜†β˜†β˜†β˜†2001β†’ Residue 313
NM_021083.4(XK):c.880T>C (p.Cys294Arg)Pathogenic
XK-related neurodegenerative disease
β˜†β˜†β˜†β˜†2001β†’ Residue 294
NM_021083.4(XK):c.941G>A (p.Trp314Ter)Pathogenic
XK-related neurodegenerative disease
β˜†β˜†β˜†β˜†2001β†’ Residue 314
NM_021083.4(XK):c.895C>T (p.Gln299Ter)Pathogenic
XK-related neurodegenerative disease
β˜†β˜†β˜†β˜†2001β†’ Residue 299
NM_021083.4(XK):c.1013del (p.Phe338fs)Pathogenic
XK-related neurodegenerative disease
β˜†β˜†β˜†β˜†1999β†’ Residue 338
NM_021083.4(XK):c.509-1G>APathogenic
XK-related neurodegenerative disease
β˜†β˜†β˜†β˜†1994
NM_021083.4(XK):c.508+1G>APathogenic
XK-related neurodegenerative disease
β˜†β˜†β˜†β˜†1994
NM_021083.4(XK):c.771G>A (p.Trp257Ter)Likely pathogenic
Elevated circulating creatine kinase concentration
β˜†β˜†β˜†β˜†β†’ Residue 257
View on ClinVar β†—
Related Genes
EDN3Protein interaction78%KELProtein interaction78%VPS13AProtein interaction73%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
35%
Heart
34%
Lung
5%
Liver
4%
Ovary
2%
Gene Interaction Network
Click a node to explore
XKEDN3KELVPS13A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P51811
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.45Moderately Constrained
pLIβ“˜
0.98Intolerant
Observed/Expected LoF0.14 [0.06–0.45]
RankingsWhere XK stands among ~20K protein-coding genes
  • #10,113of 20,598
    Most Researched41
  • #2,535of 5,498
    Most Pathogenic Variants14
  • #2,508of 17,882
    Most Constrained (LOEUF)0.45 Β· top quartile
Genes detectedXK
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation.
PMID: 37955115
Circ Res Β· 2023
1.00
2
XK aprosencephaly.
PMID: 9571288
Clin Dysmorphol Β· 1998
0.90
3
Autologous exosome facilitates load and target delivery of bioactive peptides to repair spinal cord injury.
PMID: 37056263
Bioact Mater Β· 2023
0.80
4
mRNA-based Vaccines Targeting the T-cell Epitope-rich Domain of Epstein Barr Virus Latent Proteins Elicit Robust Anti-Tumor Immunity in Mice.
PMID: 37890462
Adv Sci (Weinh) Β· 2023
0.70
5
Liquidambaric acid inhibits Wnt/Ξ²-catenin signaling and colon cancer via targeting TNF receptor-associated factor 2.
PMID: 35108540
Cell Rep Β· 2022
0.60