Information on CXCR4

Basic details

Approved name: C-X-C motif chemokine receptor 4
Alt. names: chemokine (C-X-C motif), receptor 4 (fusin), chemokine (C-X-C motif) receptor 4

Location: 2q22.1: 136114349 - 136119177 (-)
Gene type: protein_coding, 7 transcripts.

Scores: LoFtool: 0.329000 | pLI: 0.42745098 | LOEUF: 1.052

HGNC: 2561

NCBI: 7852, RefSeq: NG_011587.1

Ensembl: ENSG00000121966.8

LRG_51 | Status: public

OMIM: 162643

Expression | ProteinAtlas

Normal function

CXCR4 encodes C-X-C chemokine receptor type 4. When CXCL12/SDF-1 is bound to this receptor, it leads to an elevated intracellular calcium ion concentration resulting in an enhanced activation of MAPK1/MAPK3. CXCR4 is involved in regulation of cell migration and induction of inflammatory response by secretion of TNF by monocytes after contact with bacterial lipopolysaccharide (LPS). It plays also a role in hematopoiesis, developement of cardiac ventricular septum, cerebellum and gastrointestinal vasculatization. CXCR4 acts also as a coreceptor for human immunodeficiency virus-1 (HIV-1) and as a primary receptor for HIV-2.

Dysfunction and disease

Monoallelic variants in CXCR4 can cause WHIM syndrome-1 (WHIMS1) (MIM:193670), a form of immunodeficiency characterized by neutropenia and hypogammaglobulinemia. Special about WHIMS1 is a higher susceptibility to extensive human papillomavirus (HPV) infection compared to other immunodeficiences. Bone marrow aspirates of affected individuals showed lots of mature myeloid cells, also called myelokathexis. Kathethis means retention indicating that mature myeloid cells are retained in the bone marro w leading to cytopenia in the bloodstream. The most common variant causing 50% of WHIMS1 cases is R334X. This variant leads to a truncation of 19 amino acids in the cytoplasmatic tail, a crucial region for regulation of receptor function (PMID:12692554, 31313072). Other variants associated with WHIMS1 are E343X, S338X, Ser339fs342Ter and Gly323fs343Ter. All of these variants gain stop codons affecting the cytoplasmatic tail of the protein. [Load More]

[Reviewed by Nele Viehmann on 2022-02-11 10:31:58]

Associated conditions

Acronym	Condition's_name	MOI	Mode_of_action	OMIM_ID	No.cases
WHIMS1	Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome	AD		193670	0 (0 fams)

Please mind that full curation (inclusion of all published patients) of this gene has not started yet. Please contact us if you want to volunteer.

Transcripts of CXCR4

Name	ENSEMBL_ID	LRG_ID	CCDS_ID	MANE	Transcript.type	Exons	Canonical	CDS_length	REFSEQ_ID
202	ENST00000409817.1		CCDS33295		protein_coding	1	No	1895	NM_001008540
201	ENST00000241393.4	1	CCDS46420	Select	protein_coding	2	Yes	1668	NM_001348056,NM_001348059,NM_003467
204	ENST00000696136.1				protein_coding	2	No		XM_047445802
205	ENST00000696137.1				protein_coding	2	No		NM_001348060

Published variants

Found 1 variants

Var.name	Exon/Intron	cDNA_pos.	CDS_change	Prot.change	Var.type	Var.class.	Patients
R338*	EX1	1316	c.1012C>T	p.Arg338Ter	stop_gained	Pathogenic	0

Please mind that full curation (inclusion of all published variants) of this gene has not started yet. Please contact us if you want to volunteer.

Diagnostic pitfalls & paradigms

Considerations to take into account when analyzing this gene

Year	Paradigm ⓘ	PMID	Notes
-	Regions of Homology	-
2015	Somatic reversion	26459672	chromothripsis
-	Cryptic splicing	-	Unreported or not recorded in our DB.
-	Uniparental disomy	-	Unreported or not recorded in our DB.
-	Mosaicism	-	Unreported or not recorded in our DB.
-	Incomplete penetrance	-	Unreported or not recorded in our DB.
-	Di-/oligo-genic inheritance	-	Unreported or not recorded in our DB.

References linked to variants in CXCR4

ID	Year	Title	Journal	PMID	Variants
432	2003	Mutations in the chemokine receptor gene CXCR4 are associate...	Nat. Genet.	12692554	1
433	2015	Chromothriptic cure of WHIM syndrome...	Cell	25662009	1

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