Functional neutrophil defect

Summary

Functional neutrophil defect (MONDO:0015978) is a disease (an umbrella term covering 5 Mondo subtypes) with 19 GWAS associations across 7 studies. A subtype of leukocyte disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Umbrella term: 5 Mondo subtypes
• GWAS associations: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	functional neutrophil defect
Mondo ID	MONDO:0015978
Orphanet	183681
ICD-11	808756909
SNOMED CT	105600002
UMLS	C5924997
MedGen	1863601
GARD	0020321
Is cancer (heuristic)	no

Also known as: neutrophil disease · neutrophilopathy

Data availability: 19 GWAS associations (7 studies).

Disease family

This is a subtype of leukocyte disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › functional neutrophil defect

Related subtypes (22): human monocytic ehrlichiosis, B cell deficiency, leukopenia, B-cell neoplasm, dendritic cell sarcoma, human granulocytic anaplasmosis, T-cell leukemia, phagocyte bactericidal dysfunction, EBV-positive T-cell lymphoproliferative disorder of childhood, small intestinal enteropathy-associated T-cell lymphoma, pituitary gland basophil adenoma, leukostasis, mastocytosis, hereditary neutrophilia, Pelger-Huet anomaly, thymoma type B, POEMS syndrome, Langerhans cell histiocytosis, subcutaneous panniculitis-like T-cell lymphoma, eosinophil peroxidase deficiency, eosinophil disorder, mast cell activation syndrome

Subtypes (5): Papillon-Lefevre disease, specific granule deficiency, myeloperoxidase deficiency, neutrophil immunodeficiency syndrome, leukocyte adhesion deficiency

Genetics & variants

GWAS landscape

19 GWAS associations across 7 studies. Top hits map to 10 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs77375493	9e-78	JAK2	G	2.11
rs2814778	1e-60	ACKR1, CADM3-AS1	T	0.45
rs12451897	1e-34	MED24	G	0.13
rs35272691	3e-34	PSMD3-AS1	T	0.14
rs4766578	2e-18	ATXN2	T	0.09
chr1:162693795	6e-15		A	0.27
rs3917932	1e-14	CSF3R	C	0.08
rs445	2e-14	CDK6	C	0.14
rs404891	4e-14	CD1D - CD1A	G	0.14
rs7534426	4e-14	NHLH1 - RNU4-42P	T	0.16
rs7705526	3e-13	TERT	C	0.08
rs11264765	2e-11	FCRL5 - FCRL4	G	0.13
chr1:161220666	3e-11		C	0.27
rs17150998	8e-07	MAGI2	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475812	Verma A	2024	18,630	406,005	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475811	Verma A	2024	4,513	110,702	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479989	Verma A	2024	4,513	110,702	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435825	Zhou W	2018	3,788	401,375	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90477468	Verma A	2024	1,883	54,968	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90652204	Liu TY	2025	768	225,499	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90043689	Jiang L	2021	135	456,213	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	11

MAF distribution

Bucket	Variants
common (>=0.05)	12
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	1

Functional consequences

Consequence	Count
intron_variant	7
unknown	2
intergenic_variant	2
missense_variant	1
5_prime_UTR_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs77375493	9	5073770	G>A,C,T	0	missense_variant	JAK2	9e-78	Tier 1: coding
rs2814778	1	159204893	T>A,C	0.171	5_prime_UTR_variant	ACKR1, CADM3-AS1	1e-60	Tier 2: splice/UTR
rs12451897	17	40023022	G>C,T	0.321	intron_variant	MED24	1e-34	Tier 4: intronic/intergenic
rs35272691	17	40001588	T>A,C	0.368	intron_variant	PSMD3-AS1	3e-34	Tier 4: intronic/intergenic
rs4766578	12	111466567	T>A	0.496	intron_variant	ATXN2	2e-18	Tier 4: intronic/intergenic
chr1:162693795				0.131			6e-15	Tier 4: intronic/intergenic
rs3917932	1	36478315	C>G,T	0.42	intron_variant	CSF3R	1e-14	Tier 4: intronic/intergenic
rs445	7	92779056	C>T	0.109	intron_variant	CDK6	2e-14	Tier 4: intronic/intergenic
rs404891	1	158234741	G>A,C,T	0.144	intergenic_variant	CD1D - CD1A	4e-14	Tier 4: intronic/intergenic
rs7534426	1	160376511	T>A,G	0.122	regulatory_region_variant	NHLH1 - RNU4-42P	4e-14	Tier 3: regulatory
rs7705526	5	1285859	C>A,G,T	0.337	intron_variant	TERT	3e-13	Tier 4: intronic/intergenic
rs11264765	1	157572659	G>C	0.124	intergenic_variant	FCRL5 - FCRL4	2e-11	Tier 4: intronic/intergenic
chr1:161220666				0.082			3e-11	Tier 4: intronic/intergenic
rs17150998	7	78550738	T>C		intron_variant	MAGI2	8e-07	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

No druggable-target or therapeutic data for this disease’s cohort.

Clinical trials & evidence

Clinical trials

Clinical trials: 0.