Neutropenia

Summary

Neutropenia (MONDO:0001475) is a disease caused by ELANE (GenCC Definitive), with 40 cohort genes (30 GWAS associations across 18 studies) and 178 clinical trials. Top therapeutic interventions include filgrastim, docetaxel anhydrous, and pegfilgrastim.

At a glance

• Causal gene: ELANE (GenCC Definitive)
• Cohort genes: 40
• GWAS associations: 30
• ClinVar variants: 35
• Clinical trials: 178

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neutropenia
Mondo ID	MONDO:0001475
MeSH	D009503
DOID	DOID:1227
ICD-11	926492960
SNOMED CT	303011007
UMLS	C0853697
MedGen	163121
Is cancer (heuristic)	no

Also known as: neutropenia · neutropenic disorder

Data availability: 35 ClinVar variants · 30 GWAS associations (18 studies) · 3 GenCC gene-disease records · 1 HPO phenotype · 2 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › leukopenia › agranulocytosis › neutropenia

Related subtypes (1): acquired agranulocytosis

Subtypes (4): transient neonatal neutropenia, constitutional neutropenia, neonatal alloimmune neutropenia, ELANE-related neutropenia

Genetics & variants

GWAS landscape

30 GWAS associations across 18 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2814778	8e-72	ACKR1, CADM3-AS1	T	0.94
rs11871747	2e-15	MED24	T	0.15
chr1:162862846	3e-14		A	0.44
rs561592613	5e-14	CDK5RAP2	C	1.98
rs6686197	2e-13	UBE2Q1 - CHRNB2	G	0.3
rs4794822	7e-13	PSMD3-AS1	C	0.17
rs530741354	6e-12	TPM1 - LACTB	A	2.1
rs185884229	2e-11	WDR76	C	2.41
rs569025	2e-11	LMNA	A	0.19
rs4402118	2e-11	NES - CRABP2	C	0.27
rs7522783	2e-11	FCRLB - RN7SL466P	T	0.18
rs531549040	3e-11	ZNF800 - LINC03012	G	2.08
rs4784750	2e-08	NLRC5	T	1.38
rs16972207	3e-08	TNFSF13B	G	1.54
rs11583606	2e-07	TGFBR3	T	7
rs874404	2e-07	ARHGEF3	?
rs146378328	3e-07	EPHX4	G	8.31
rs825249	3e-07	CEDORA, CDH13, HSBP1	?	2.2
rs143843248	1e-06	PTPRO	T	7.3
rs73163933	1e-06	STARD13 - RFC3	A	5.36
rs2799083	2e-06	TGFB2	?	2.27
rs12526817	3e-06	NT5DC1	?	2.22
rs7915425	4e-06	RPS26P39 - LINC02641	?	2.34
rs9835060	5e-06	UPK1B	?	2.59
rs17117434	5e-06	DLC1 - SGCZ	?	2.86
rs9601722	5e-06	PTMAP5 - GYG1P2	?	3.4
rs1941238	7e-06	RN7SL97P - SS18	?	2.34

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90079716	Backman JD	2021	4,407	382,668	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083702	Backman JD	2021	4,407	382,668	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90475817	Verma A	2024	4,197	443,510	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435827	Zhou W	2018	3,184	401,375	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90475816	Verma A	2024	1,983	118,200	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479985	Verma A	2024	1,983	118,200	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90244025	Fasching PA	2022	1,679	0	Identification of Two Genetic Loci Associated with Leukopenia after Chemotherapy in Breast Cancer Patients.
GCST90651991	Liu TY	2025	1,542	225,499	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90043688	Jiang L	2021	1,373	454,975	A generalized linear mixed model association tool for biobank-scale data.
GCST90476489	Verma A	2024	394	59,154	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	26

MAF distribution

Bucket	Variants
common (>=0.05)	23
low_freq (0.01-0.05)	0
rare (<0.01)	4
unknown	0

Functional consequences

Consequence	Count
intron_variant	18
intergenic_variant	7
5_prime_UTR_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2814778	1	159204893	T>A,C	0.169	5_prime_UTR_variant	ACKR1, CADM3-AS1	8e-72	Tier 2: splice/UTR
rs11871747	17	40021029	T>A,C	0.376	intron_variant	MED24	2e-15	Tier 4: intronic/intergenic
chr1:162862846				0.167			3e-14	Tier 4: intronic/intergenic
rs561592613	9	120416425	C>T	0.001	intron_variant	CDK5RAP2	5e-14	Tier 4: intronic/intergenic
rs6686197	1	154562141	G>C,T	0.324	intergenic_variant	UBE2Q1 - CHRNB2	2e-13	Tier 4: intronic/intergenic
rs4794822	17	40000459	C>G,T	0.385	intron_variant	PSMD3-AS1	7e-13	Tier 4: intronic/intergenic
rs530741354	15	63082375	A>G	0	intron_variant	TPM1 - LACTB	6e-12	Tier 4: intronic/intergenic
rs185884229	15	43827468	C>T	0.001	intron_variant	WDR76	2e-11	Tier 4: intronic/intergenic
rs569025	1	156134206	A>C	0.182	intron_variant	LMNA	2e-11	Tier 4: intronic/intergenic
rs4402118	1	156693685	C>G,T	0.332	intron_variant	NES - CRABP2	2e-11	Tier 4: intronic/intergenic
rs7522783	1	161729270	T>C,G	0.189	intergenic_variant	FCRLB - RN7SL466P	2e-11	Tier 4: intronic/intergenic
rs531549040	7	127437166	G>A	0	intergenic_variant	ZNF800 - LINC03012	3e-11	Tier 4: intronic/intergenic
rs4784750	16	57022152	G>A,T	0.273	intron_variant	NLRC5	2e-08	Tier 4: intronic/intergenic
rs16972207	13	108276718	C>G,T	0.185	intron_variant	TNFSF13B	3e-08	Tier 4: intronic/intergenic
rs11583606	1	91883690	C>T	0.05	intron_variant	TGFBR3	2e-07	Tier 4: intronic/intergenic
rs874404	3	56895038	C>A,T	0.05	intron_variant	ARHGEF3	2e-07	Tier 4: intronic/intergenic
rs146378328	1	92062490	A>C,G	0.05	intron_variant	EPHX4	3e-07	Tier 4: intronic/intergenic
rs825249	16	83768694	T>C,G	0.05	intron_variant	CEDORA, CDH13, HSBP1	3e-07	Tier 4: intronic/intergenic
rs143843248	12	15480878	C>T	0.05	intron_variant	PTPRO	1e-06	Tier 4: intronic/intergenic
rs73163933	13	33393883	G>A	0.05	intron_variant	STARD13 - RFC3	1e-06	Tier 4: intronic/intergenic
rs2799083	1	218408275	T>C	0.05	intron_variant	TGFB2	2e-06	Tier 4: intronic/intergenic
rs12526817	6	116188473	C>A,T	0.05	intron_variant	NT5DC1	3e-06	Tier 4: intronic/intergenic
rs7915425	10	123256985	T>A,C	0.05	intergenic_variant	RPS26P39 - LINC02641	4e-06	Tier 4: intronic/intergenic
rs9835060	3	119189379	A>C,G	0.05	intron_variant	UPK1B	5e-06	Tier 4: intronic/intergenic
rs17117434	8	13768307	G>C,T	0.05	intergenic_variant	DLC1 - SGCZ	5e-06	Tier 4: intronic/intergenic
rs9601722	13	81838491	T>A,C	0.05	intergenic_variant	PTMAP5 - GYG1P2	5e-06	Tier 4: intronic/intergenic
rs1941238	18	25864505	T>A,C,G	0.05	intergenic_variant	RN7SL97P - SS18	7e-06	Tier 4: intronic/intergenic

ClinVar germline variants

35 retrieved; paginated sample, class counts are floors:

12 likely benign, 11 uncertain significance, 4 pathogenic, 3 benign/likely benign, 2 likely pathogenic, 1 benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1684623	NM_001258392.3(CLPB):c.1167+5G>A	CLPB	Pathogenic	no assertion criteria provided
187786	NM_001258392.3(CLPB):c.1159C>T (p.Arg387Ter)	CLPB	Pathogenic	criteria provided, multiple submitters, no conflicts
245598	NM_001972.4(ELANE):c.597+5G>A	ELANE	Pathogenic	criteria provided, multiple submitters, no conflicts
374163	NM_152564.5(VPS13B):c.4545del (p.Ser1516fs)	VPS13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56635	NM_152564.5(VPS13B):c.11239C>T (p.Gln3747Ter)	VPS13B	Pathogenic	criteria provided, multiple submitters, no conflicts
1301867	NM_013275.6(ANKRD11):c.6349_6362del (p.Pro2117fs)	ANKRD11	Likely pathogenic	no assertion criteria provided
1803189	NM_001972.4(ELANE):c.413T>A (p.Leu138Gln)	ELANE	Likely pathogenic	criteria provided, single submitter
68290	NM_001164277.2(SLC37A4):c.81T>A (p.Asn27Lys)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267924	46;XY;t(16;20)(q23.1;p11.22)		Uncertain significance	criteria provided, single submitter
267990	46;XX;inv(2)(q13q14.2)		Uncertain significance	criteria provided, single submitter
812887	NM_006118.4(HAX1):c.182T>G (p.Phe61Cys)	HAX1	Uncertain significance	criteria provided, single submitter
1679869	NM_001161403.3(LIMS2):c.802+1G>A	LIMS2	Uncertain significance	no assertion criteria provided
1679868	NM_007183.4(PKP3):c.118C>T (p.Arg40Trp)	PKP3	Uncertain significance	no assertion criteria provided
2672472	NM_006019.4(TCIRG1):c.2405G>A (p.Arg802Gln)	TCIRG1	Uncertain significance	criteria provided, single submitter
305806	NM_006019.4(TCIRG1):c.1508A>G (p.Asn503Ser)	TCIRG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
305817	NM_006019.4(TCIRG1):c.2162T>A (p.Ile721Asn)	TCIRG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4076145	NM_006019.4(TCIRG1):c.2118+5G>A	TCIRG1	Uncertain significance	no assertion criteria provided
1679870	NM_006537.4(USP3):c.941T>G (p.Phe314Cys)	USP3	Uncertain significance	no assertion criteria provided
932238	NM_022575.4(VPS16):c.540G>T (p.Trp180Cys)	VPS16	Uncertain significance	no assertion criteria provided
718379	NM_001183.6(ATP6AP1):c.539G>A (p.Arg180His)	ATP6AP1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1679864	NM_001109659.2(C16orf92):c.128G>A (p.Arg43Lys)	C16orf92	Likely benign	no assertion criteria provided
703138	NM_152274.5(CCNQ):c.338G>A (p.Arg113His)	CCNQ	Likely benign	criteria provided, multiple submitters, no conflicts
1679858	NM_001710.6(CFB):c.1942A>T (p.Lys648Ter)	CFB	Likely benign	no assertion criteria provided
1679866	NM_004284.6(CHD1L):c.1954G>A (p.Ala652Thr)	CHD1L	Likely benign	no assertion criteria provided
1679867	NM_001136018.4(EPHX1):c.1004C>T (p.Thr335Met)	EPHX1	Benign	no assertion criteria provided
1043778	NM_004523.4(KIF11):c.3053A>G (p.His1018Arg)	KIF11	Likely benign	criteria provided, multiple submitters, no conflicts
726756	NM_004523.4(KIF11):c.77+5G>C	KIF11	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1679865	NM_005462.5(MAGEC1):c.2T>C (p.Met1Thr)	LOC126863334	Likely benign	criteria provided, single submitter
1679859	NM_001401501.2(MUC16):c.27739T>C (p.Ser9247Pro)	MUC16	Likely benign	criteria provided, single submitter
932519	NM_006468.8(POLR3C):c.251G>A (p.Arg84Gln)	POLR3C	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 28 · 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
ELANE	Definitive	Autosomal dominant	neutropenia	5
SRP19	Moderate	Autosomal recessive	neutropenia

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELANE	Orphanet:2686	Cyclic neutropenia
ELANE	Orphanet:486	Autosomal dominant severe congenital neutropenia
SRP19	Orphanet:486	Autosomal dominant severe congenital neutropenia
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
SLC34A1	Orphanet:157215	Hereditary hypophosphatemic rickets with hypercalciuria
SLC34A1	Orphanet:244305	Dominant hypophosphatemia with nephrolithiasis or osteoporosis
SLC34A1	Orphanet:300547	Autosomal recessive infantile hypercalcemia
SLC34A1	Orphanet:3337	Primary Fanconi renotubular syndrome
SS18	Orphanet:3273	Synovial sarcoma
TCIRG1	Orphanet:1782	Dysosteosclerosis
TCIRG1	Orphanet:210110	Intermediate osteopetrosis
TCIRG1	Orphanet:486	Autosomal dominant severe congenital neutropenia
TCIRG1	Orphanet:667	Autosomal recessive malignant osteopetrosis
TGFB2	Orphanet:60030	Loeys-Dietz syndrome
TGFB2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TGFBR3	Orphanet:231160	Familial cerebral saccular aneurysm
HAX1	Orphanet:99749	Kostmann syndrome
ANKRD11	Orphanet:2332	KBG syndrome
ANKRD11	Orphanet:261250	16q24.3 microdeletion syndrome
VPS13B	Orphanet:193	Cohen syndrome
COL10A1	Orphanet:174	Metaphyseal chondrodysplasia, Schmid type
CCNQ	Orphanet:140952	Syndactyly-telecanthus-anogenital and renal malformations syndrome
CLPB	Orphanet:445038	3-methylglutaconic aciduria-neonatal cataract-neurologic involvement-congenital neutropenia syndrome
CLPB	Orphanet:486	Autosomal dominant severe congenital neutropenia
EPHX1	Orphanet:238475	Familial hypercholanemia
SLC37A4	Orphanet:79259	Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib
KIF11	Orphanet:2526	Microcephaly-lymphedema-chorioretinopathy syndrome
ATP6AP1	Orphanet:692790	ATP6AP1-CDG

Cohort genes → proteins

40 cohort genes, 40 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	16
multi_evidence	24

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ELANE	HGNC:3309	ENSG00000197561	P08246	Neutrophil elastase	gencc,clinvar
SRP19	HGNC:11300	ENSG00000153037	P09132	Signal recognition particle 19 kDa protein	gencc
CFB	HGNC:1037	ENSG00000243649	P00751	Complement factor B	clinvar
SLC34A1	HGNC:11019	ENSG00000131183	Q06495	Sodium-dependent phosphate transport protein 2A	clinvar
SS18	HGNC:11340	ENSG00000141380	Q15532	Protein SSXT	gwas
TCIRG1	HGNC:11647	ENSG00000110719	Q13488	V-type proton ATPase 116 kDa subunit a 3	clinvar
TGFB2	HGNC:11768	ENSG00000092969	P61812	Transforming growth factor beta-2 proprotein	gwas
TGFBR3	HGNC:11774	ENSG00000069702	Q03167	Transforming growth factor beta receptor type 3	gwas
TLE2	HGNC:11838	ENSG00000065717	Q04725	Transducin-like enhancer protein 2	clinvar
UPK1B	HGNC:12578	ENSG00000114638	O75841	Uroplakin-1b	gwas
USP3	HGNC:12626	ENSG00000140455	Q9Y6I4	Ubiquitin carboxyl-terminal hydrolase 3	clinvar
SGCZ	HGNC:14075	ENSG00000185053	Q96LD1	Zeta-sarcoglycan	gwas
VPS16	HGNC:14584	ENSG00000215305	Q9H269	Vacuolar protein sorting-associated protein 16 homolog	clinvar
MUC16	HGNC:15582	ENSG00000181143	Q8WXI7	Mucin-16	clinvar
LIMS2	HGNC:16084	ENSG00000072163	Q7Z4I7	LIM and senescent cell antigen-like-containing domain protein 2	clinvar
HAX1	HGNC:16915	ENSG00000143575	O00165	HCLS1-associated protein X-1	clinvar
CHD1L	HGNC:1916	ENSG00000131778	Q86WJ1	ATP-dependent chromatin remodeler CHD1L	clinvar
STARD13	HGNC:19164	ENSG00000133121	Q9Y3M8	StAR-related lipid transfer protein 13	gwas
ANKRD11	HGNC:21316	ENSG00000167522	Q6UB99	Ankyrin repeat domain-containing protein 11	clinvar
NT5DC1	HGNC:21556	ENSG00000178425	Q5TFE4	5’-nucleotidase domain-containing protein 1	gwas
TSPYL4	HGNC:21559	ENSG00000187189	Q9UJ04	Testis-specific Y-encoded-like protein 4	gwas
VPS13B	HGNC:2183	ENSG00000132549	Q7Z7G8	Intermembrane lipid transfer protein VPS13B	clinvar
COL10A1	HGNC:2185	ENSG00000123500	Q03692	Collagen alpha-1(X) chain	gwas
EPHX4	HGNC:23758	ENSG00000172031	Q8IUS5	Epoxide hydrolase 4	gwas
ZNF521	HGNC:24605	ENSG00000198795	Q96K83	Zinc finger protein 521	gwas
C8orf48	HGNC:26345	ENSG00000164743	Q96LL4	Uncharacterized protein C8orf48	gwas
FIMP1	HGNC:26346	ENSG00000167194	Q96LL3	Fertilization-influencing membrane protein	clinvar
TEX55	HGNC:26553	ENSG00000163424	Q96M34	Testis-specific expressed protein 55	gwas
CCNQ	HGNC:28434	ENSG00000262919	Q8N1B3	Cyclin-Q	clinvar
ZC3H3	HGNC:28972	ENSG00000014164	Q8IXZ2	Zinc finger CCCH domain-containing protein 3	clinvar
POLR3C	HGNC:30076	ENSG00000186141	Q9BUI4	DNA-directed RNA polymerase III subunit RPC3	clinvar
CLPB	HGNC:30664	ENSG00000162129	Q9H078	Mitochondrial disaggregase	clinvar
EPHX1	HGNC:3401	ENSG00000143819	P07099	Epoxide hydrolase 1	clinvar
SLC37A4	HGNC:4061	ENSG00000137700	O43826	Glucose-6-phosphate exchanger SLC37A4	clinvar
GPR26	HGNC:4481	ENSG00000154478	Q8NDV2	G-protein coupled receptor 26	gwas
KIF11	HGNC:6388	ENSG00000138160	P52732	Kinesin-like protein KIF11	clinvar
ATP6AP1	HGNC:868	ENSG00000071553	Q15904	V-type proton ATPase subunit S1	clinvar
PKP3	HGNC:9025	ENSG00000184363	Q9Y446	Plakophilin-3	clinvar
B4GALT4	HGNC:927	ENSG00000121578	O60513	Beta-1,4-galactosyltransferase 4	gwas
PTPRU	HGNC:9683	ENSG00000060656	Q92729	Receptor-type tyrosine-protein phosphatase U	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELANE	Neutrophil elastase	Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes.
SRP19	Signal recognition particle 19 kDa protein	Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER).
CFB	Complement factor B	Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the…
SLC34A1	Sodium-dependent phosphate transport protein 2A	Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane.
SS18	Protein SSXT	Appears to function synergistically with RBM14 as a transcriptional coactivator.
TCIRG1	V-type proton ATPase 116 kDa subunit a 3	Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
TGFB2	Transforming growth factor beta-2 proprotein	Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.
TGFBR3	Transforming growth factor beta receptor type 3	Cell surface receptor that regulates diverse cellular processes including cell proliferation, differentiation, migration, and apoptosis.
TLE2	Transducin-like enhancer protein 2	Transcriptional corepressor that binds to a number of transcription factors.
UPK1B	Uroplakin-1b	Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells.
USP3	Ubiquitin carboxyl-terminal hydrolase 3	Deubiquitinase that plays a role in several cellular processes including transcriptional regulation, cell cycle progression or innate immunity.
SGCZ	Zeta-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
VPS16	Vacuolar protein sorting-associated protein 16 homolog	Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways.
MUC16	Mucin-16	Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces.
LIMS2	LIM and senescent cell antigen-like-containing domain protein 2	Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors.
HAX1	HCLS1-associated protein X-1	Recruits the Arp2/3 complex to the cell cortex and regulates reorganization of the cortical actin cytoskeleton via its interaction with KCNC3 and the Arp2/3 complex.
CHD1L	ATP-dependent chromatin remodeler CHD1L	ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage.
STARD13	StAR-related lipid transfer protein 13	GTPase-activating protein for RhoA, and perhaps for Cdc42.
ANKRD11	Ankyrin repeat domain-containing protein 11	Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells.
VPS13B	Intermembrane lipid transfer protein VPS13B	Mediates the transfer of lipids between membranes at organelle contact sites.
COL10A1	Collagen alpha-1(X) chain	Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage.
ZNF521	Zinc finger protein 521	Transcription factor that can both act as an activator or a repressor depending on the context.
FIMP1	Fertilization-influencing membrane protein	May play a role in sperm-oocyte fusion during fertilization.
CCNQ	Cyclin-Q	Activating cyclin for the cyclin-associated kinase CDK10.
ZC3H3	Zinc finger CCCH domain-containing protein 3	Required for the export of polyadenylated mRNAs from the nucleus.
POLR3C	DNA-directed RNA polymerase III subunit RPC3	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
CLPB	Mitochondrial disaggregase	Functions as a regulatory ATPase and participates in secretion/protein trafficking process.
EPHX1	Epoxide hydrolase 1	Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
SLC37A4	Glucose-6-phosphate exchanger SLC37A4	Inorganic phosphate and glucose-6-phosphate antiporter of the endoplasmic reticulum.
GPR26	G-protein coupled receptor 26	Orphan receptor.
KIF11	Kinesin-like protein KIF11	Motor protein required for establishing a bipolar spindle and thus contributing to chromosome congression during mitosis.
ATP6AP1	V-type proton ATPase subunit S1	Accessory subunit of the proton-transporting vacuolar (V)-ATPase protein pump, which is required for luminal acidification of secretory vesicles.
PKP3	Plakophilin-3	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
B4GALT4	Beta-1,4-galactosyltransferase 4	Galactose (Gal) transferase involved in the synthesis of terminal N-acetyllactosamine (LacNac) unit present on glycan chains of glycoproteins and glycosphingolipids.
PTPRU	Receptor-type tyrosine-protein phosphatase U	Tyrosine-protein phosphatase which dephosphorylates CTNNB1.

Protein-family classification

Druggable: 9 · Difficult: 6 · Unknown: 25 · Druggable fraction: 0.23

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
Protease	3	2.8×	0.656
Phosphatase	1	2.1×	0.656
Transporter	1	1.9×	0.656
Scaffold/PPI	3	1.3×	0.656
Other/Unknown	25	1.1×	0.656
Enzyme (other)	3	0.9×	0.878
Transcription factor	3	0.6×	0.878
GPCR	1	0.6×	0.878

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELANE	Protease	yes	3.4.21.37	Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA
SRP19	Other/Unknown	no		Signal_recog_particle_SRP19, SRP19-like_sf
CFB	Protease	yes	3.4.21.47	Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
SLC34A1	Other/Unknown	no		Na/Pi_transpt
SS18	Other/Unknown	no		SS18_N
TCIRG1	Other/Unknown	no		V-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka
TGFB2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGFb2
TGFBR3	Other/Unknown	no		ZP_dom, ZP_dom_CS, ZP-C_dom
TLE2	Scaffold/PPI	no		WD40_rpt, Groucho/TLE_N, Groucho_enhance
UPK1B	Other/Unknown	no		Tetraspanin_EC2_sf, Tetraspanin/Peripherin
USP3	Protease	yes		Peptidase_C19_UCH, Znf_UBP, Znf_RING/FYVE/PHD
SGCZ	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta
VPS16	Other/Unknown	no		Vps16_C, Vps16_N, VPS16
MUC16	Other/Unknown	no		SEA_dom, MUC16, SEA_dom_sf
LIMS2	Transcription factor	no		Znf_LIM, PINCH-1-4-like, LIMS1/2-like_LIM1
HAX1	Other/Unknown	no		HAX-1
CHD1L	Other/Unknown	no		SNF2_N, Helicase_C-like, DNA/RNA_helicase_DEAH_CS
STARD13	Other/Unknown	no		RhoGAP_dom, SAM, START_lipid-bd_dom
ANKRD11	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, ANKRD11
NT5DC1	Other/Unknown	no		HAD-SF_hydro_IG_5-nucl, HAD_sf, HAD-like_sf
TSPYL4	Other/Unknown	no		NAP, NAP-like_sf
VPS13B	Other/Unknown	no		VPS13_VAB, VPS13_N, VPS13B
COL10A1	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom
EPHX4	Other/Unknown	no		AB_hydrolase_1, Epox_hydrolase-like, AB_hydrolase_fold
ZNF521	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
C8orf48	Other/Unknown	no		DUF4606
FIMP1	Other/Unknown	no		FIMP
TEX55	Other/Unknown	no		Tex55, TEX55_DD
CCNQ	Other/Unknown	no		Cyclin_N, Cyclin-like_dom, Cyclin-like_sf
ZC3H3	Transcription factor	no		Znf_CCCH, Znf_CCCH_sf
POLR3C	Other/Unknown	no		RNA_pol_III_Rpc82_C, RNA_pol_III_RPC82-rel_HTH, WH-like_DNA-bd_sf
CLPB	Scaffold/PPI	no		ClpA/B, Ankyrin_rpt, AAA+_ATPase
EPHX1	Enzyme (other)	yes	3.3.2.9	AB_hydrolase_1, Epox_hydrolase-like, Epoxide_hydrolase
SLC37A4	Transporter	yes		Sugar_P_transporter, MFS, MFS_dom
GPR26	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, GPR26/78-like
KIF11	Enzyme (other)	yes	5.6.1.3	Kinesin_motor_dom, Kinesin_motor_CS, Kinesin-assoc_MT-bd_dom
ATP6AP1	Other/Unknown	no		Ac45_acc_su, VAS1_LD, VAS1/VOA1_TM
PKP3	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold
B4GALT4	Enzyme (other)	yes	2.4.1.275	Galactosyl_T, Galactosyl_T_C, Galactosyl_T_N
PTPRU	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, MAM_dom

Expression context

Cohort genes with no expression data: 0.

36 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)	40
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	4
right lobe of liver	3
cerebellar hemisphere	3
male germ line stem cell (sensu Vertebrata) in testis	3
primordial germ cell in gonad	3
sural nerve	3
stromal cell of endometrium	3
tendon of biceps brachii	3
Brodmann (1909) area 23	3
left testis	3
right testis	3
monocyte	2
liver	2
kidney epithelium	2
adrenal tissue	2
right adrenal gland	2
right adrenal gland cortex	2
granulocyte	2
right hemisphere of cerebellum	2
oocyte	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELANE	124	tissue_specific	marker	bone marrow, bone marrow cell, monocyte
SRP19	169	ubiquitous	marker	adenohypophysis, body of pancreas, islet of Langerhans
CFB	134	broad	marker	right lobe of liver, liver, gall bladder
SLC34A1	52	tissue_specific	marker	nephron tubule, adult mammalian kidney, kidney epithelium
SS18	291	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland
TCIRG1	148	ubiquitous	marker	granulocyte, blood, spleen
TGFB2	206	ubiquitous	marker	calcaneal tendon, tendon, cartilage tissue
TGFBR3	288	ubiquitous	marker	renal glomerulus, metanephric glomerulus, synovial joint
TLE2	293	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
UPK1B	160	broad	marker	palpebral conjunctiva, epithelium of nasopharynx, nasopharynx
USP3	284	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
SGCZ	70	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, oocyte, secondary oocyte
VPS16	275	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, cerebellar hemisphere
MUC16	113	broad	marker	nasal cavity epithelium, epithelium of bronchus, bronchus
LIMS2	237	ubiquitous	marker	apex of heart, lower esophagus muscularis layer, lower esophagus
HAX1	295	ubiquitous	marker	apex of heart, heart right ventricle, hindlimb stylopod muscle
CHD1L	233	ubiquitous	marker	primordial germ cell in gonad, C1 segment of cervical spinal cord, cerebellar hemisphere
STARD13	256	ubiquitous	marker	sural nerve, tibial nerve, adrenal tissue
ANKRD11	278	ubiquitous	marker	tendon of biceps brachii, sural nerve, stromal cell of endometrium
NT5DC1	255	ubiquitous	marker	corpus callosum, kidney epithelium, inferior vagus X ganglion
TSPYL4	285	ubiquitous	marker	Brodmann (1909) area 23, endothelial cell, cerebellar vermis
VPS13B	291	ubiquitous	marker	sural nerve, nipple, bronchial epithelial cell
COL10A1	162	broad	marker	tibia, periodontal ligament, buccal mucosa cell
EPHX4	159	broad	yes	primordial germ cell in gonad, middle temporal gyrus, Brodmann (1909) area 23
ZNF521	240	ubiquitous	marker	cerebellar vermis, buccal mucosa cell, calcaneal tendon
C8orf48	162	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, stromal cell of endometrium
FIMP1	114		yes	right testis, left testis, male germ line stem cell (sensu Vertebrata) in testis
TEX55	26	tissue_specific	yes	left testis, right testis, testis
CCNQ	255	ubiquitous	marker	tendon of biceps brachii, left ventricle myocardium, myocardium
ZC3H3	184	ubiquitous	marker	right lobe of liver, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLPB	5,095
KIF11	3,788
SLC34A1	3,362
CHD1L	3,332
POLR3C	2,985
ELANE	2,758
EPHX1	2,678
TGFBR3	2,412
ANKRD11	2,384
HAX1	2,243

Intra-cohort edges

A	B	Sources
ATP6AP1	TCIRG1	intact
B4GALT4	NT5DC1	string_interaction
B4GALT4	SLC34A1	biogrid_interaction
C8orf48	SGCZ	string_interaction
CLPB	HAX1	intact
ELANE	HAX1	string_interaction
EPHX1	EPHX4	string_interaction
NT5DC1	TSPYL4	string_interaction
SLC37A4	VPS13B	string_interaction

Structural data

PDB: 18 · AlphaFold-only: 22 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF11	P52732	62
ELANE	P08246	38
POLR3C	Q9BUI4	32
CFB	P00751	26
SLC37A4	O43826	25
TGFB2	P61812	11
SRP19	P09132	9
ATP6AP1	Q15904	9
CHD1L	Q86WJ1	7
CLPB	Q9H078	7
MUC16	Q8WXI7	4
STARD13	Q9Y3M8	3
PTPRU	Q92729	2
SS18	Q15532	1
TGFBR3	Q03167	1
VPS16	Q9H269	1
LIMS2	Q7Z4I7	1
COL10A1	Q03692	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EPHX1	P07099	95.06
EPHX4	Q8IUS5	92.95
GPR26	Q8NDV2	90.90
B4GALT4	O60513	90.78
CCNQ	Q8N1B3	88.81
NT5DC1	Q5TFE4	88.76
UPK1B	O75841	86.32
TCIRG1	Q13488	83.52
SGCZ	Q96LD1	80.59
USP3	Q9Y6I4	79.40
SLC34A1	Q06495	72.24
PKP3	Q9Y446	69.24
TLE2	Q04725	68.40
C8orf48	Q96LL4	65.98
FIMP1	Q96LL3	65.84
TSPYL4	Q9UJ04	65.77
ZNF521	Q96K83	61.75
HAX1	O00165	60.06
ZC3H3	Q8IXZ2	52.45
TEX55	Q96M34	48.94
ANKRD11	Q6UB99	39.44
VPS13B	Q7Z7G8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 133. Enrichment computed across 40 evidence-associated genes (26 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 26 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TGFBR3 regulates TGF-beta signaling	2	109.8×	0.018	TGFB2, TGFBR3
Insulin receptor recycling	2	29.3×	0.074	TCIRG1, ATP6AP1
Transferrin endocytosis and recycling	2	28.3×	0.074	TCIRG1, ATP6AP1
Signaling by TGFBR3	2	28.3×	0.074	TGFB2, TGFBR3
TGF-beta receptor signaling activates SMADs	2	25.1×	0.075	TGFB2, TGFBR3
FGFR1 ligand binding and activation	1	219.6×	0.086	TGFBR3
Defective SLC34A1 causes hypophosphatemic nephrolithiasis/osteoporosis 1 (NPHLOP1)	1	219.6×	0.086	SLC34A1
Regulation of Complement cascade	2	17.9×	0.091	ELANE, CFB
TGFBR3 regulates FGF2 signaling	1	146.4×	0.097	TGFBR3
Type II Na+/Pi cotransporters	1	109.8×	0.097	SLC34A1
TGFBR3 regulates activin signaling	1	109.8×	0.097	TGFBR3
Signaling by TGF-beta Receptor Complex	2	15.4×	0.097	TGFB2, TGFBR3
Collagen degradation	2	13.5×	0.097	ELANE, COL10A1
Alternative complement activation	1	87.8×	0.100	CFB
Expression of NOTCH2NL genes	1	87.8×	0.100	ELANE
Non-integrin membrane-ECM interactions	2	11.9×	0.101	SGCZ, COL10A1
Activation of C3 and C5	1	48.8×	0.148	CFB
FGFR1b ligand binding and activation	1	48.8×	0.148	TGFBR3
Signaling by TGFB family members	2	8.9×	0.148	TGFB2, TGFBR3
Formation of the posterior neural plate	1	43.9×	0.149	ZNF521
SARS-CoV-2 modulates autophagy	1	39.9×	0.149	VPS16
Formation of the anterior neural plate	1	39.9×	0.149	ZNF521
TGFBR3 PTM regulation	1	36.6×	0.149	TGFBR3
Signaling by FGFR1	1	31.4×	0.149	TGFBR3
Signaling by Activin	1	29.3×	0.149	TGFBR3
FGFR1c ligand binding and activation	1	29.3×	0.149	TGFBR3
N-Glycan antennae elongation	1	29.3×	0.149	B4GALT4
Repression of WNT target genes	1	27.4×	0.149	TLE2
Defective GALNT3 causes HFTC	1	27.4×	0.149	MUC16
Defective GALNT12 causes CRCS1	1	27.4×	0.149	MUC16

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 36 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
biosynthetic process of antibacterial peptides active against Gram-negative bacteria	1	468.1×	0.038	ELANE
response to silver ion	1	468.1×	0.038	TCIRG1
regulation of timing of catagen	1	468.1×	0.038	TGFB2
epicardium-derived cardiac fibroblast cell development	1	468.1×	0.038	TGFBR3
positive regulation of activation-induced cell death of T cells	1	468.1×	0.038	TGFB2
dentin mineralization	1	468.1×	0.038	TCIRG1
hydrocarbon catabolic process	1	468.1×	0.038	EPHX1
regulation of apoptotic process involved in outflow tract morphogenesis	1	468.1×	0.038	TGFB2
negative regulation of cholangiocyte proliferation	1	468.1×	0.038	LIMS2
negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	1	468.1×	0.038	TGFB2
lactosylceramide biosynthetic process	1	234.1×	0.038	B4GALT4
obsolete membrane lipid metabolic process	1	234.1×	0.038	B4GALT4
protein catabolic process in the vacuole	1	234.1×	0.038	TCIRG1
cardioblast differentiation	1	234.1×	0.038	TGFB2
slow endocytic recycling	1	234.1×	0.038	VPS13B
response to luteinizing hormone	1	234.1×	0.038	TGFBR3
memory T cell activation	1	234.1×	0.038	TCIRG1
indole metabolic process	1	234.1×	0.038	SLC34A1
uterine wall breakdown	1	234.1×	0.038	TGFB2
neutrophil-mediated killing of fungus	1	234.1×	0.038	ELANE
endothelial tube lumen extension	1	234.1×	0.038	STARD13
gentamycin metabolic process	1	234.1×	0.038	SLC34A1
arsenate ion transmembrane transport	1	234.1×	0.038	SLC34A1
substantia propria of cornea development	1	234.1×	0.038	TGFB2
cholangiocyte proliferation	1	234.1×	0.038	LIMS2
positive regulation of phosphate transmembrane transport	1	234.1×	0.038	SLC34A1
phosphate ion transmembrane transport	2	66.9×	0.038	SLC34A1, SLC37A4
cardiac epithelial to mesenchymal transition	2	66.9×	0.038	TGFB2, TGFBR3
secondary palate development	2	66.9×	0.038	TGFB2, TGFBR3
neuron fate commitment	2	44.6×	0.038	TGFB2, ZNF521

Therapeutics

Drugs indicated for this disease

5 approved, 10 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Efbemalenograstim Alfa	Approved (phase 4)
Filgrastim	Approved (phase 4)
Lipegfilgrastim	Approved (phase 4)
Pegfilgrastim	Approved (phase 4)
Posaconazole	Approved (phase 4)
Alcohol	Phase 3 (in late-stage trials)
Amoxicillin	Phase 3 (in late-stage trials)
Chlorhexidine	Phase 3 (in late-stage trials)
Ciprofloxacin	Phase 3 (in late-stage trials)
Dextrose	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Eflapegrastim	Phase 3 (in late-stage trials)
Lithium Carbonate	Phase 3 (in late-stage trials)
Mavorixafor	Phase 3 (in late-stage trials)
Plinabulin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cytarabine, Etoposide, Idarubicin, Lintuzumab.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 4 · Phased (≥1): 6 · Undrugged: 34

Druggability breadth: 15 of 40 evidence-associated genes (38%) 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
ELANE	BOCEPREVIR
CFB	IPTACOPAN
SLC34A1	SODIUM PHOSPHATE, DIBASIC, ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ELANE	11	4
KIF11	6	3
SLC34A1	2	4
EPHX1	2	2
CFB	1	4
TGFB2	1	2
SRP19	0	0
SS18	0	0
TCIRG1	0	0
TGFBR3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BOCEPREVIR	4	ELANE
TELAPREVIR	4	ELANE
BORTEZOMIB	4	ELANE
IPTACOPAN	4	CFB
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1
EPIGALOCATECHIN GALLATE	3	ELANE
QUERCETIN	3	ELANE
SIVELESTAT	3	ELANE
GOSSYPOL	3	KIF11
LUTEOLIN	2	ELANE
MIDESTEINE	2	ELANE
FRESELESTAT	2	ELANE
DELANZOMIB	2	ELANE
ALVELESTAT	2	ELANE
GALUNISERTIB	2	TGFB2
TRICLOCARBAN	2	EPHX1
AR9281	2	EPHX1
AZD-4877	2	KIF11
LITRONESIB	2	KIF11
ISPINESIB	2	KIF11
FILANESIB	2	KIF11
SB-743921	1	KIF11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

Symbol	Assays	Type breakdown
ELANE	801	Binding:758, Functional:35, ADMET:6, Toxicity:2
KIF11	193	Binding:185, Functional:8
CFB	33	Binding:33
EPHX1	30	Binding:18, ADMET:12
NT5DC1	11	Binding:11
SLC34A1	8	Binding:7, Functional:1
ATP6AP1	7	Binding:7
SLC37A4	5	Binding:5
CHD1L	4	Binding:4
TGFB2	3	Binding:3
USP3	3	Binding:3
HAX1	3	Binding:3
SRP19	2	Binding:2
GPR26	2	Binding:2
PTPRU	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ELANE	3.4.21.37	leukocyte elastase
CFB	3.4.21.47	alternative-complement-pathway C3/C5 convertase
EPHX1	3.3.2.9	microsomal epoxide hydrolase
KIF11	5.6.1.3	plus-end-directed kinesin ATPase
B4GALT4	2.4.1.275	neolactotriaosylceramide beta-1,4-galactosyltransferase
PTPRU	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ELANE	801
KIF11	193

Pharmacogenomics

Cohort genes with a PharmGKB record: 40; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

23 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)
BOCEPREVIR	4	ELANE
TELAPREVIR	4	ELANE
BORTEZOMIB	4	ELANE
IPTACOPAN	4	CFB
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1
EPIGALOCATECHIN GALLATE	3	ELANE
QUERCETIN	3	ELANE
SIVELESTAT	3	ELANE
GOSSYPOL	3	KIF11
LUTEOLIN	2	ELANE
MIDESTEINE	2	ELANE
FRESELESTAT	2	ELANE
DELANZOMIB	2	ELANE
ALVELESTAT	2	ELANE
GALUNISERTIB	2	TGFB2
TRICLOCARBAN	2	EPHX1
AR9281	2	EPHX1
AZD-4877	2	KIF11
LITRONESIB	2	KIF11
ISPINESIB	2	KIF11
FILANESIB	2	KIF11
SB-743921	1	KIF11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	ELANE, CFB, SLC34A1
B	Phased (≥1) drug, not yet approved	3	TGFB2, EPHX1, KIF11
C	Druggable family + PDB, no drug	2	SLC37A4, PTPRU
D	Druggable family + AlphaFold only, no drug	3	USP3, GPR26, B4GALT4
E	Difficult family or no structure, no drug	29	SRP19, SS18, TCIRG1, TGFBR3, TLE2, UPK1B, SGCZ, VPS16, MUC16, LIMS2 (+19 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HAX1	3	ELANE
EPHX4	0	EPHX1
SRP19	2	—
SS18	0	—
TCIRG1	0	—
TGFBR3	0	—
TLE2	0	—
UPK1B	0	—
USP3	3	—
SGCZ	0	—
VPS16	0	—
MUC16	0	—
LIMS2	0	—
CHD1L	4	—
STARD13	0	—
ANKRD11	0	—
NT5DC1	11	—
TSPYL4	0	—
VPS13B	0	—
COL10A1	0	—
ZNF521	0	—
C8orf48	0	—
FIMP1	0	—
TEX55	0	—
CCNQ	0	—
ZC3H3	0	—
POLR3C	0	—
CLPB	0	—
SLC37A4	5	—
GPR26	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 178.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	53
PHASE2	40
PHASE3	31
PHASE1	24
PHASE4	16
PHASE1/PHASE2	12
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT06056297	PHASE3	RECRUITING	A Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections
NCT00001338	PHASE3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00002658	PHASE3	UNKNOWN	Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002719	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia
NCT00003739	PHASE3	COMPLETED	Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy
NCT00020865	PHASE3	UNKNOWN	Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
NCT00035594	PHASE3	COMPLETED	Pegfilgrastim as Support to Advanced Breast Cancer Patients Receiving Chemotherapy
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00107081	PHASE3	TERMINATED	Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
NCT00445497	PHASE3	UNKNOWN	Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
NCT00529282	PHASE3	TERMINATED	A Study of Ceftobiprole in Patients With Fever and Neutropenia.
NCT00627393	PHASE3	COMPLETED	Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
NCT00770172	PHASE3	COMPLETED	G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy
NCT00784368	PHASE3	COMPLETED	A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
NCT00806351	PHASE3	TERMINATED	An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01307579	PHASE3	COMPLETED	Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
NCT01371656	PHASE3	COMPLETED	Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
NCT01560195	PHASE3	UNKNOWN	A Study of Pegylated rhG-CSF as Support to Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy Receiving Chemotherapy
NCT01611051	PHASE3	COMPLETED	A Study Comparing Pegylated rhG-CSF and rhG-CSF as Support to Breast Cancer Patients Receiving Chemotherapy
NCT02231879	PHASE2/PHASE3	COMPLETED	Plerixafor Versus G-CSF in the Treatment of People With WHIM Syndrome
NCT02238873	PHASE3	UNKNOWN	Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma
NCT02414581	PHASE3	COMPLETED	Mouthwash With Chlorhexidine 0.12%/Ethyl Alcohol 7% Compared to Ethyl Alcohol 7%

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FILGRASTIM	4	19
DOCETAXEL ANHYDROUS	4	14
PEGFILGRASTIM	4	14
EFBEMALENOGRASTIM ALFA	4	7
CASPOFUNGIN	4	4
EFLAPEGRASTIM	4	4
ANIDULAFUNGIN	4	3
CIPROFLOXACIN	4	3
CYCLOPHOSPHAMIDE ANHYDROUS	4	3
IDARUBICIN	4	3
LEVOFLOXACIN ANHYDROUS	4	3
MERCAPTOPURINE ANHYDROUS	4	3
MICAFUNGIN	4	3
MITOXANTRONE HYDROCHLORIDE	4	3
PLERIXAFOR	4	3
VORICONAZOLE	4	3
AMIFOSTINE	4	2
AMPHOTERICIN B	4	2
AMSACRINE	4	2
CEFEPIME HYDROCHLORIDE	4	2
CEFTOBIPROLE MEDOCARIL FREE ACID	4	2
CYTARABINE	4	2
DAPTOMYCIN	4	2
ETOPOSIDE	4	2
ITRACONAZOLE	4	2
LETERMOVIR	4	2
MAVORIXAFOR	4	2
POSACONAZOLE	4	2
THIOGUANINE	4	2
ALCOHOL	4	1