susceptibility to HIV infection

Summary

susceptibility to HIV infection (MONDO:0004951) is a disease with 14 cohort genes. The dominant Reactome pathway is Chemokine receptors bind chemokines (7 cohort genes).

At a glance

• Cohort genes: 14
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	susceptibility to HIV infection
Mondo ID	MONDO:0004951
OMIM	609423
NCIT	C14220
UMLS	C1836230
MedGen	332156
Is cancer (heuristic)	no

Also known as: AIDS, delayed/rapid progression to · AIDS, rapid progression to · AIDS, resistance to · AIDS, slow progression to · HIV infection, resistance to · HIV type 1, susceptibility to · HIV-1 disease, delayed progression of · HIV-1 disease, rapid progression of · HIV-1 viremia, susceptibility to · HIV/AIDS, susceptibility to · HIV1 infection, resistance to · HIV1, resistance to · rapid progression to AIDS from HIV1 infection

Data availability: 34 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › susceptibility to HIV infection

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

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

34 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 6 protective, 4 conflicting classifications of pathogenicity, 2 benign, 1 benign/likely benign, 1 protective; risk factor, 1 conflicting classifications of pathogenicity; protective, 1 benign; protective

ClinVar	Variant (HGVS)	Gene	Classification	Review
5408	NC_000019.10:g.7747847A>G	CD209	protective; risk factor	no assertion criteria provided
8189	NM_000579.4(CCR5):c.-301+246A>G	CCR5	Conflicting classifications of pathogenicity; protective	no assertion criteria provided
626118	NM_000418.4(IL4R):c.1160C>T (p.Ser387Leu)	IL4R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
456662	NM_000572.3(IL10):c.43G>A (p.Gly15Arg)	LOC128462409	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
495314	NM_003265.3(TLR3):c.889C>G (p.Leu297Val)	TLR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
842830	NM_003265.3(TLR3):c.1987G>A (p.Glu663Lys)	TLR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8367	NC_000017.11:g.34284427=	CCL11	protective	no assertion criteria provided
14205	NC_000017.11:g.34253212=	CCL2	protective	no assertion criteria provided
14206	NM_002982.4(CCL2):c.77-109=	CCL2	protective	no assertion criteria provided
625906	NM_001123396.4(CCR2):c.*1179G>A	CCR2	Uncertain significance	criteria provided, multiple submitters, no conflicts
625907	NM_001123396.4(CCR2):c.1043C>T (p.Thr348Met)	CCR2	Uncertain significance	criteria provided, single submitter
8188	NM_001394783.1(CCR5):c.303T>A (p.Cys101Ter)	CCR5	protective	no assertion criteria provided
992556	NM_001394783.1(CCR5):c.187A>T (p.Ser63Cys)	CCR5	Uncertain significance	criteria provided, multiple submitters, no conflicts
8191	NM_001394783.1(CCR5):c.180G>T (p.Arg60Ser)	CCR5AS	protective	no assertion criteria provided
625909	NM_021155.4(CD209):c.642G>C (p.Glu214Asp)	CD209	Uncertain significance	criteria provided, multiple submitters, no conflicts
827974	NM_021155.4(CD209):c.566A>T (p.Gln189Leu)	CD209	Uncertain significance	criteria provided, multiple submitters, no conflicts
992523	NM_001171174.1(CX3CR1):c.10C>G (p.Pro4Ala)	CX3CR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
625926	NM_199168.4(CXCL12):c.*2C>T	CXCL12	Uncertain significance	criteria provided, single submitter
8762	NM_199168.4(CXCL12):c.*531G>A	CXCL12	protective	no assertion criteria provided
2500018	NM_000634.3(CXCR1):c.838C>T (p.Arg280Cys)	CXCR1	Uncertain significance	criteria provided, single submitter
625927	NM_000634.3(CXCR1):c.608G>A (p.Arg203Gln)	CXCR1	Uncertain significance	criteria provided, single submitter
992524	NM_000634.3(CXCR1):c.3G>A (p.Met1Ile)	CXCR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
827982	NM_000418.4(IL4R):c.1774G>T (p.Val592Leu)	IL4R	Uncertain significance	criteria provided, multiple submitters, no conflicts
4075743	NM_001318399.1(NUP160):c.38C>T (p.Pro13Leu)	LOC130005685	Uncertain significance	criteria provided, single submitter
4075742	NM_015231.3(NUP160):c.3343G>C (p.Ala1115Pro)	NUP160	Uncertain significance	criteria provided, single submitter
4056090	NM_006267.5(RANBP2):c.6110C>T (p.Ser2037Leu)	RANBP2	Uncertain significance	criteria provided, single submitter
4072410	NM_006267.5(RANBP2):c.3518A>C (p.Glu1173Ala)	RANBP2	Uncertain significance	criteria provided, single submitter
569628	NM_003265.3(TLR3):c.176C>A (p.Thr59Asn)	TLR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
570922	NM_003265.3(TLR3):c.554C>T (p.Ala185Val)	TLR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
6662	NM_003265.3(TLR3):c.1660C>T (p.Pro554Ser)	TLR3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TLR3	Orphanet:1930	Herpes simplex virus encephalitis
NUP160	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
IL10	Orphanet:117	Behçet disease
IL10	Orphanet:238569	Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome
IL10	Orphanet:536	Systemic lupus erythematosus
RANBP2	Orphanet:178342	Inflammatory myofibroblastic tumor
RANBP2	Orphanet:263524	Acute necrotizing encephalopathy of childhood
RANBP2	Orphanet:88619	Familial acute necrotizing encephalopathy

Cohort genes → proteins

14 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CCL11	HGNC:10610	ENSG00000172156	P51671	Eotaxin	clinvar
CCL2	HGNC:10618	ENSG00000108691	P13500	C-C motif chemokine 2	clinvar
CXCL12	HGNC:10672	ENSG00000107562	P48061	Stromal cell-derived factor 1	clinvar
TLR3	HGNC:11849	ENSG00000164342	O15455	Toll-like receptor 3	clinvar
CCR2	HGNC:1603	ENSG00000121807	P41597	C-C chemokine receptor type 2	clinvar
CCR5	HGNC:1606	ENSG00000160791	P51681	C-C chemokine receptor type 5	clinvar
CD209	HGNC:1641	ENSG00000090659	Q9NNX6	CD209 antigen	clinvar
NUP160	HGNC:18017	ENSG00000030066	Q12769	Nuclear pore complex protein Nup160	clinvar
CX3CR1	HGNC:2558	ENSG00000168329	P49238	CX3C chemokine receptor 1	clinvar
CCR5AS	HGNC:54398	ENSG00000223552		CCR5 antisense RNA	clinvar
IL10	HGNC:5962	ENSG00000136634	P22301	Interleukin-10	clinvar
IL4R	HGNC:6015	ENSG00000077238	P24394	Interleukin-4 receptor subunit alpha	clinvar
CXCR1	HGNC:6026	ENSG00000163464	P25024	C-X-C chemokine receptor type 1	clinvar
RANBP2	HGNC:9848	ENSG00000153201	P49792	E3 SUMO-protein ligase RanBP2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCL11	Eotaxin	Chemokine that plays a central role in both allergic and non-allergic inflammatory reactions by inducing the migration of different leukocyte types including eosinophils, basophils, macrophages and dendritic cells.
CCL2	C-C motif chemokine 2	Acts as a ligand for C-C chemokine receptor CCR2.
CXCL12	Stromal cell-derived factor 1	Chemoattractant active on T-lymphocytes and monocytes but not neutrophils.
TLR3	Toll-like receptor 3	Key component of innate and adaptive immunity.
CCR2	C-C chemokine receptor type 2	Key functional receptor for CCL2 but can also bind CCL7, and CCL12.
CCR5	C-C chemokine receptor type 5	Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level.
CD209	CD209 antigen	Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response.
NUP160	Nuclear pore complex protein Nup160	Functions as a component of the nuclear pore complex (NPC).
CX3CR1	CX3C chemokine receptor 1	Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte cells; CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune response, inflammation, cell adhesion and chem…
IL10	Interleukin-10	Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.
IL4R	Interleukin-4 receptor subunit alpha	Receptor for both interleukin 4 and interleukin 13.
CXCR1	C-X-C chemokine receptor type 1	Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor.
RANBP2	E3 SUMO-protein ligase RanBP2	E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I.

Protein-family classification

Druggable: 5 · Difficult: 1 · Unknown: 8 · Druggable fraction: 0.36

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	4	6.8×	0.009
Antibody/Immunoglobulin	1	2.1×	0.761
Other/Unknown	8	1.0×	0.761
Transcription factor	1	0.6×	0.836

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CCL11	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
CCL2	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
CXCL12	Other/Unknown	no		Chemokine_IL8-like_dom, CXC_Chemokine_domain, Interleukin_8-like_sf
TLR3	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
CCR2	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR2
CCR5	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR5
CD209	Other/Unknown	no		C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
NUP160	Other/Unknown	no		Nucleoporin_Nup160, TPR_NUP160_M, TPR_NUP160_C
CX3CR1	GPCR	yes		GPCR_Rhodpsn, Chemokine_CX3CR1, GPCR_Rhodpsn_7TM
CCR5AS	Other/Unknown	no
IL10	Other/Unknown	no		IL-10, 4_helix_cytokine-like_core, IL-10_CS
IL4R	Antibody/Immunoglobulin	yes		Hempt_rcpt_S_F1_CS, FN3_dom, Ig-like_fold
CXCR1	GPCR	yes		Chemokine_CXCR_1/2, GPCR_Rhodpsn, Chemokine_CXCR1
RANBP2	Transcription factor	no		Ran_bind_dom, Znf_RanBP2, Cyclophilin-type_PPIase_dom

Expression context

Cohort genes with no expression data: 0.

13 cohort genes 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)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	3
gall bladder	2
leukocyte	2
monocyte	2
type B pancreatic cell	2
mucosa of paranasal sinus	2
caecum	1
cardia of stomach	1
pylorus	1
islet of Langerhans	1
vena cava	1
mammary duct	1
pericardium	1
synovial joint	1
jejunal mucosa	1
palpebral conjunctiva	1
placenta	1
mononuclear cell	1
epithelium of nasopharynx	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCL11	128	broad	marker	pylorus, cardia of stomach, caecum
CCL2	252	ubiquitous	marker	vena cava, gall bladder, islet of Langerhans
CXCL12	275	ubiquitous	marker	synovial joint, pericardium, mammary duct
TLR3	232	ubiquitous	marker	jejunal mucosa, palpebral conjunctiva, placenta
CCR2	162	broad	marker	monocyte, mononuclear cell, leukocyte
CCR5	194	broad	marker	type B pancreatic cell, olfactory bulb, epithelium of nasopharynx
CD209	188	tissue_specific	marker	lymph node, superficial temporal artery, decidua
NUP160	278	ubiquitous	marker	oocyte, mucosa of paranasal sinus, secondary oocyte
CX3CR1	255	broad	marker	granulocyte, inferior vagus X ganglion, superior vestibular nucleus
CCR5AS	118	broad	yes	colonic epithelium, monocyte, leukocyte
IL10	158	broad	marker	vermiform appendix, gall bladder, cartilage tissue
IL4R	245	ubiquitous	marker	granulocyte, mucosa of stomach, right lung
CXCR1	148	broad	marker	blood, granulocyte, type B pancreatic cell
RANBP2	294	ubiquitous	marker	endothelial cell, sperm, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 14.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RANBP2	7,348
IL10	6,185
CCL2	5,749
CXCL12	4,892
TLR3	4,305
CCR5	3,406
CCR2	3,331
IL4R	2,970
CX3CR1	2,636
CXCR1	2,224

Intra-cohort edges

A	B	Sources
CCL11	CCL2	biogrid_interaction, intact
CCL11	CXCL12	biogrid_interaction, intact
CCL2	CCR2	string_interaction
CCL2	CCR5	string_interaction
CCL2	CX3CR1	string_interaction
CCL2	CXCR1	string_interaction
CCR2	CCR5	string_interaction
CCR2	CXCL12	string_interaction
CCR2	CXCR1	string_interaction
CCR5	CXCL12	string_interaction
CX3CR1	CXCL12	string_interaction
CXCL12	CXCR1	string_interaction
IL10	IL4R	string_interaction
NUP160	RANBP2	biogrid_interaction

Structural data

PDB: 13 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CXCL12	P48061	34
RANBP2	P49792	33
CCR5	P51681	26
TLR3	O15455	20
CCL2	P13500	14
CD209	Q9NNX6	14
IL4R	P24394	10
IL10	P22301	9
CCR2	P41597	7
CXCR1	P25024	5
CCL11	P51671	4
NUP160	Q12769	4
CX3CR1	P49238	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 106. Enrichment computed across 14 evidence-associated genes (13 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 13 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	7	100.8×	2e-11	CCL11, CCL2, CXCL12, CCR2, CCR5, CX3CR1, CXCR1
Interleukin-10 signaling	4	71.7×	1e-05	CCL2, CCR2, CCR5, IL10
Class A/1 (Rhodopsin-like receptors)	5	28.5×	1e-05	CCL11, CCL2, CXCL12, CCR2, CCR5
Peptide ligand-binding receptors	5	28.5×	1e-05	CCL11, CCL2, CXCL12, CCR2, CCR5
GPCR ligand binding	5	24.7×	2e-05	CCL11, CCL2, CXCL12, CCR2, CCR5
Interleukin-4 and Interleukin-13 signaling	4	31.7×	1e-04	CCL11, CCL2, IL10, IL4R
Signaling by GPCR	5	15.4×	2e-04	CCL11, CCL2, CXCL12, CCR2, CCR5
G alpha (i) signalling events	5	15.0×	2e-04	CXCL12, CCR2, CCR5, CX3CR1, CXCR1
Signaling by Interleukins	4	19.7×	4e-04	CCL11, CCL2, CCR2, CCR5
RSV-host interactions	3	36.1×	7e-04	TLR3, CD209, CX3CR1
Cytokine Signaling in Immune system	4	12.6×	0.002	CCL11, CCL2, CCR2, CCR5
IPs transport between nucleus and cytosol	2	58.6×	0.003	NUP160, RANBP2
IP3 and IP4 transport between cytosol and nucleus	2	58.6×	0.003	NUP160, RANBP2
IP6 and IP7 transport between cytosol and nucleus	2	58.6×	0.003	NUP160, RANBP2
Transport of Ribonucleoproteins into the Host Nucleus	2	54.9×	0.003	NUP160, RANBP2
Regulation of Glucokinase by Glucokinase Regulatory Protein	2	54.9×	0.003	NUP160, RANBP2
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	2	54.9×	0.003	NUP160, RANBP2
NEP/NS2 Interacts with the Cellular Export Machinery	2	53.2×	0.003	NUP160, RANBP2
Nuclear import of Rev protein	2	51.7×	0.003	NUP160, RANBP2
Vpr-mediated nuclear import of PICs	2	51.7×	0.003	NUP160, RANBP2
Transport of the SLBP independent Mature mRNA	2	50.2×	0.003	NUP160, RANBP2
SUMOylation of SUMOylation proteins	2	50.2×	0.003	NUP160, RANBP2
Transport of the SLBP Dependant Mature mRNA	2	48.8×	0.003	NUP160, RANBP2
Rev-mediated nuclear export of HIV RNA	2	48.8×	0.003	NUP160, RANBP2
Nuclear Pore Complex (NPC) Disassembly	2	47.5×	0.003	NUP160, RANBP2
SUMOylation of ubiquitinylation proteins	2	45.0×	0.004	NUP160, RANBP2
NS1 Mediated Effects on Host Pathways	2	43.9×	0.004	NUP160, RANBP2
Transport of Mature mRNA Derived from an Intronless Transcript	2	41.8×	0.004	NUP160, RANBP2
TLR3 deficiency - HSE	1	878.5×	0.004	TLR3
Viral Messenger RNA Synthesis	2	39.9×	0.004	NUP160, RANBP2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
immune response	8	29.0×	1e-08	CXCL12, CCR2, CCR5, CD209, CX3CR1, IL10, IL4R, CXCR1
chemotaxis	6	62.7×	4e-08	CCL11, CCL2, CXCL12, CCR2, CCR5, CX3CR1
cell chemotaxis	5	71.2×	5e-07	CCL11, CXCL12, CCR2, CCR5, CX3CR1
chemokine-mediated signaling pathway	4	99.7×	3e-06	CCL11, CCL2, CXCL12, CCR2
positive regulation of cytosolic calcium ion concentration	5	45.0×	3e-06	CCL2, CCR2, CCR5, CX3CR1, CXCR1
dendritic cell chemotaxis	3	228.8×	1e-05	CCR2, CCR5, CXCR1
positive regulation of monocyte chemotaxis	3	185.2×	2e-05	CXCL12, CCR2, CX3CR1
calcium-mediated signaling	4	56.4×	2e-05	CCR2, CCR5, CX3CR1, CXCR1
cellular response to lipopolysaccharide	4	30.1×	2e-04	CCL2, CCR5, CX3CR1, IL10
cellular defense response	3	73.4×	3e-04	CCR2, CCR5, CX3CR1
inflammatory response to wounding	2	324.1×	4e-04	TLR3, CCR2
G protein-coupled receptor signaling pathway	5	13.9×	4e-04	CCL2, CXCL12, CCR5, CX3CR1, CXCR1
positive regulation of endothelial cell proliferation	3	53.3×	5e-04	CCL11, CXCL12, IL10
positive regulation of glutamate receptor signaling pathway	2	235.7×	7e-04	CCL2, CCR2
viral genome replication	2	172.8×	0.001	CCL2, CD209
leukocyte chemotaxis	2	162.0×	0.001	CX3CR1, IL10
positive regulation of calcium ion import	2	144.0×	0.001	CCL2, CXCL12
intracellular calcium ion homeostasis	3	33.5×	0.001	CCL11, CXCL12, CCR2
positive regulation of macrophage activation	2	129.6×	0.002	IL10, IL4R
cellular homeostasis	2	123.5×	0.002	CCL2, CCR2
eosinophil chemotaxis	2	112.7×	0.002	CCL11, CCL2
positive regulation of synaptic transmission, glutamatergic	2	96.0×	0.003	CCL2, CCR2
defense response to protozoan	2	92.6×	0.003	IL10, IL4R
monocyte chemotaxis	2	89.4×	0.003	CCL2, CCR2
inflammatory response	4	11.6×	0.003	CCL11, CCL2, CCR2, CCR5
cell adhesion	4	11.5×	0.003	CCL11, CCL2, CXCL12, CX3CR1
positive regulation of immunoglobulin production	2	74.1×	0.004	IL10, IL4R
positive regulation of T cell activation	2	68.2×	0.004	CCL2, CCR2
nucleocytoplasmic transport	2	60.3×	0.005	NUP160, RANBP2
sensory perception of pain	2	57.6×	0.005	CCL2, CCR2

Therapeutics

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 8

Druggability breadth: 13 of 14 evidence-associated genes (93%) 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
CXCL12	PLERIXAFOR
CCR2	CISPLATIN
CCR5	TERFENADINE
CX3CR1	FLUOXETINE HYDROCHLORIDE
CXCR1	DEXIBUPROFEN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCR2	17	4
CCR5	15	4
CXCR1	9	4
CX3CR1	8	4
CCL2	2	3
CXCL12	2	4
CCL11	0	0
TLR3	0	0
CD209	0	0
NUP160	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PLERIXAFOR	4	CCR2, CXCL12
DIFLUNISAL	4	CXCL12
CISPLATIN	4	CCR2
NIFEDIPINE	4	CCR2
AMIODARONE	4	CCR2
DISULFIRAM	4	CCR2, CCR5
TERFENADINE	4	CCR5
ABAMETAPIR	4	CCR5
MARAVIROC	4	CCR5
FLUOXETINE HYDROCHLORIDE	4	CX3CR1
SALMETEROL	4	CX3CR1
TOLTERODINE TARTRATE	4	CX3CR1
PIMAVANSERIN	4	CX3CR1
ELAGOLIX SODIUM	4	CX3CR1
PERPHENAZINE	4	CX3CR1
DEXIBUPROFEN	4	CXCR1
DEXKETOPROFEN	4	CXCR1
CLOTRIMAZOLE	4	CXCR1
DICLOFENAC	4	CXCR1
ITRACONAZOLE	4	CXCR1
FASUDIL	3	CCL2, CCR2
CENICRIVIROC	3	CCR2, CCR5
VERCIRNON	3	CCR2
APLAVIROC	3	CCR5
APLAVIROC HYDROCHLORIDE	3	CCR5
VICRIVIROC	3	CCR5
REPARIXIN	3	CXCR1
QUERCETIN	3	CXCR1
PF-4136309	2	CCR2
ILACIRNON	2	CCR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CCR2	426	Binding:277, Functional:149
CCR5	409	Binding:243, Functional:166
CXCR1	120	Binding:85, Functional:35
TLR3	55	Binding:52, Functional:3
CXCL12	29	Binding:29
CX3CR1	26	Binding:19, Functional:7
CCL2	24	Binding:24
CD209	21	Binding:21
CCL11	1	Binding:1
NUP160	1	Binding:1
RANBP2	1	Binding:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CCR2	426
CCR5	409
CXCR1	120

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
PLERIXAFOR	4	CCR2, CXCL12
DIFLUNISAL	4	CXCL12
CISPLATIN	4	CCR2
NIFEDIPINE	4	CCR2
AMIODARONE	4	CCR2
DISULFIRAM	4	CCR2, CCR5
TERFENADINE	4	CCR5
ABAMETAPIR	4	CCR5
MARAVIROC	4	CCR5
FLUOXETINE HYDROCHLORIDE	4	CX3CR1
SALMETEROL	4	CX3CR1
TOLTERODINE TARTRATE	4	CX3CR1
PIMAVANSERIN	4	CX3CR1
ELAGOLIX SODIUM	4	CX3CR1
PERPHENAZINE	4	CX3CR1
DEXIBUPROFEN	4	CXCR1
DEXKETOPROFEN	4	CXCR1
CLOTRIMAZOLE	4	CXCR1
DICLOFENAC	4	CXCR1
ITRACONAZOLE	4	CXCR1
FASUDIL	3	CCL2, CCR2
CENICRIVIROC	3	CCR2, CCR5
VERCIRNON	3	CCR2
APLAVIROC	3	CCR5
APLAVIROC HYDROCHLORIDE	3	CCR5
VICRIVIROC	3	CCR5
REPARIXIN	3	CXCR1
QUERCETIN	3	CXCR1
PF-4136309	2	CCR2
ILACIRNON	2	CCR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	CXCL12, CCR2, CCR5, CX3CR1, CXCR1
B	Phased (≥1) drug, not yet approved	1	CCL2
C	Druggable family + PDB, no drug	1	IL4R
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	7	CCL11, TLR3, CD209, NUP160, CCR5AS, IL10, RANBP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CCL11	1	CXCL12
TLR3	55	—
CD209	21	—
NUP160	1	—
CCR5AS	0	—
IL10	0	—
IL4R	0	—
RANBP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.