XK

X-linked Kx blood group antigen, Kell and VPS13A binding protein, the group of XK related family|Blood group antigens

Basic information

Region (hg38): X:37685791-37732130

Previous symbols: [ "NA", "NAC" ]

Links

ENSG00000047597 ∙ NCBI:7504 ∙ OMIM:314850 ∙ HGNC:12811 ∙ Uniprot:P51811 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• McLeod neuroacanthocytosis syndrome (Strong), mode of inheritance: XL
• McLeod neuroacanthocytosis syndrome (Supportive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
McLeod syndrome	XL	Cardiovascular	Surveillance for cardiovascular disease (eg, dilated cardiomyopathy and arrhythmias) and early medical treatment may reduce morbidity	Cardiovascular; Hematologic; Musculoskeletal; Neurologic	13860532; 8004674; 11261514; 11761473; 17683354; 21463873

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XK gene.

• not_provided (52 variants)
• McLeod_neuroacanthocytosis_syndrome (25 variants)
• Inborn_genetic_diseases (25 variants)
• not_specified (3 variants)
• XK-related_disorder (2 variants)
• Elevated_circulating_creatine_kinase_concentration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021083.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	16	7	24
missense	1		52	3	2	58
nonsense	5	2	1			8
start loss						0
frameshift	4					4
splice donor/acceptor (+/-2bp)	2					2
Total	12	2	54	19	9

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XK	protein_coding	protein_coding	ENST00000378616	3	46372

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.954	0.0462	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.12	88	165	0.534	0.0000113	2892
Missense in Polyphen		26	67.343	0.38608		1187
Synonymous	-0.633	80	73.1	1.09	0.00000542	907
Loss of Function	2.88	0	9.65	0.00	6.68e-7	159

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in sodium-dependent transport of neutral amino acids or oligopeptides.
• Disease: DISEASE: McLeod syndrome (MLS) [MIM:300842]: A multisystem disorder characterized by the absence of red blood cell Kx antigen, weak expression of Kell red blood cell antigens, acanthocytosis, and compensated hemolysis. Most carriers of this McLeod blood group phenotype have acanthocytosis and elevated serum creatine kinase levels and are prone to develop a severe neurologic disorder resembling Huntington disease. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy. {ECO:0000269|PubMed:11761473, ECO:0000269|PubMed:11961232, ECO:0000269|PubMed:12823753}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding (Consensus)

Recessive Scores

• pRec: 0.158

Intolerance Scores

• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.76

Haploinsufficiency Scores

• pHI: 0.552
• hipred: Y
• hipred_score: 0.707
• ghis: 0.439

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Low	Medium

Mouse Genome Informatics

• Gene name: Xk
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; muscle phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: amino acid transport;cellular calcium ion homeostasis;regulation of cell size;cellular magnesium ion homeostasis;regulation of axon diameter;myelination;skeletal muscle fiber development
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: transporter activity;protein binding