WHIM syndrome 2

Summary

WHIM syndrome 2 (MONDO:0030374) is a disease caused by CXCR2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CXCR2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	WHIM syndrome 2
Mondo ID	MONDO:0030374
OMIM	619407
DOID	DOID:0060973
UMLS	C5543622
MedGen	1785594
Is cancer (heuristic)	no

Also known as: WHIMS2

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › WHIM syndrome › WHIM syndrome 2

Related subtypes (1): WHIM syndrome 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177051	NM_001557.4(CXCR2):c.968del (p.His323fs)	CXCR2	Pathogenic	no assertion criteria provided
1339556	NM_001557.4(CXCR2):c.623G>A (p.Arg208Gln)	CXCR2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CXCR2	Strong	Autosomal recessive	WHIM syndrome 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CXCR2	Orphanet:420699	Autosomal recessive severe congenital neutropenia due to CXCR2 deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CXCR2	HGNC:6027	ENSG00000180871	P25025	C-X-C chemokine receptor type 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CXCR2	C-X-C chemokine receptor type 2	Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CXCR2	GPCR	yes		Chemokine_CXCR2, Chemokine_CXCR_1/2, GPCR_Rhodpsn

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	1
granulocyte	1
periodontal ligament	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CXCR2	202	broad	marker	blood, periodontal ligament, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CXCR2	2,717

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CXCR2	P25025	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chemokine receptors bind chemokines	1	187.2×	0.016	CXCR2
G alpha (i) signalling events	1	39.0×	0.038	CXCR2
Neutrophil degranulation	1	23.1×	0.043	CXCR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
interleukin-8-mediated signaling pathway	1	16852.0×	9e-04	CXCR2
dendritic cell chemotaxis	1	991.3×	0.005	CXCR2
neutrophil activation	1	991.3×	0.005	CXCR2
receptor internalization	1	324.1×	0.009	CXCR2
cellular defense response	1	318.0×	0.009	CXCR2
neutrophil chemotaxis	1	285.6×	0.009	CXCR2
calcium-mediated signaling	1	183.2×	0.012	CXCR2
chemotaxis	1	135.9×	0.014	CXCR2
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.014	CXCR2
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.014	CXCR2
cell surface receptor signaling pathway	1	64.1×	0.023	CXCR2
immune response	1	47.1×	0.028	CXCR2
inflammatory response	1	37.7×	0.032	CXCR2
negative regulation of apoptotic process	1	34.8×	0.032	CXCR2
positive regulation of cell population proliferation	1	33.6×	0.032	CXCR2
signal transduction	1	16.1×	0.062	CXCR2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CXCR2	DEXIBUPROFEN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CXCR2	13	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DEXIBUPROFEN	4	CXCR2
DEXKETOPROFEN	4	CXCR2
CISPLATIN	4	CXCR2
DISULFIRAM	4	CXCR2
REPARIXIN	3	CXCR2
LADARIXIN	3	CXCR2
NAVARIXIN ANHYDROUS	2	CXCR2
ELUBRIXIN	2	CXCR2
AZD-8797	2	CXCR2
DANIRIXIN	2	CXCR2
SX-682	2	CXCR2
VIMNERIXIN	2	CXCR2
(R)-IBUPROPHEN	1	CXCR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CXCR2	272	Binding:201, Functional:71

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CXCR2	272

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

13 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
DEXIBUPROFEN	4	CXCR2
DEXKETOPROFEN	4	CXCR2
CISPLATIN	4	CXCR2
DISULFIRAM	4	CXCR2
REPARIXIN	3	CXCR2
LADARIXIN	3	CXCR2
NAVARIXIN ANHYDROUS	2	CXCR2
ELUBRIXIN	2	CXCR2
AZD-8797	2	CXCR2
DANIRIXIN	2	CXCR2
SX-682	2	CXCR2
VIMNERIXIN	2	CXCR2
(R)-IBUPROPHEN	1	CXCR2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CXCR2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.