Neutropenia, severe congenital, 9, autosomal dominant

Summary

Neutropenia, severe congenital, 9, autosomal dominant (MONDO:0030726) is a disease caused by CLPB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CLPB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neutropenia, severe congenital, 9, autosomal dominant
Mondo ID	MONDO:0030726
OMIM	619813
UMLS	C5676954
MedGen	1802793
GARD	0025625
Is cancer (heuristic)	no

Also known as: neutropenia, severe congenital, 9, autosomal dominant · SCN9

Data availability: 15 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 › severe congenital neutropenia › neutropenia, severe congenital, 9, autosomal dominant

Related subtypes (7): autosomal dominant severe congenital neutropenia, X-linked severe congenital neutropenia, autosomal recessive severe congenital neutropenia, neutropenia, severe congenital, 8, autosomal dominant, neutropenia, severe congenital, 10, autosomal recessive, neutropenia, severe congenital, 11, autosomal dominant, neutropenia, severe congenital, 12, autosomal recessive

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

15 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 4 pathogenic, 1 pathogenic/likely pathogenic, 1 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1676583	NM_001258392.3(CLPB):c.1073C>A (p.Thr358Lys)	CLPB	Pathogenic	no assertion criteria provided
1676584	NM_001258392.3(CLPB):c.1591C>G (p.Arg531Gly)	CLPB	Pathogenic	no assertion criteria provided
187786	NM_001258392.3(CLPB):c.1159C>T (p.Arg387Ter)	CLPB	Pathogenic	criteria provided, multiple submitters, no conflicts
2506998	NM_001258392.3(CLPB):c.449_455del (p.Val150fs)	CLPB	Pathogenic	criteria provided, single submitter
187785	NM_001258392.3(CLPB):c.1132A>G (p.Arg378Gly)	LOC126861258	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
643064	NM_001258392.3(CLPB):c.1592G>A (p.Arg531Gln)	CLPB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1676586	NM_001258392.3(CLPB):c.1768C>T (p.Arg590Cys)	CLPB	Uncertain significance	criteria provided, single submitter
1939221	NM_001258392.3(CLPB):c.428G>A (p.Arg143His)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3341069	NM_001258392.3(CLPB):c.979G>T (p.Val327Leu)	CLPB	Uncertain significance	criteria provided, single submitter
571670	NM_001258392.3(CLPB):c.844A>G (p.Met282Val)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
573047	NM_001258392.3(CLPB):c.748C>G (p.Arg250Gly)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
644249	NM_001258392.3(CLPB):c.214G>A (p.Gly72Arg)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
852817	NM_030813.6(CLPB):c.653G>C (p.Gly218Ala)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
936562	NM_001258392.3(CLPB):c.1795C>T (p.Arg599Cys)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
235218	NM_030813.6(CLPB):c.668G>A (p.Ser223Asn)	CLPB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
CLPB	Strong	Autosomal dominant	neutropenia, severe congenital, 9, autosomal dominant	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CLPB	Orphanet:445038	3-methylglutaconic aciduria-neonatal cataract-neurologic involvement-congenital neutropenia syndrome
CLPB	Orphanet:486	Autosomal dominant severe congenital neutropenia

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
CLPB	HGNC:30664	ENSG00000162129	Q9H078	Mitochondrial disaggregase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CLPB	Mitochondrial disaggregase	Functions as a regulatory ATPase and participates in secretion/protein trafficking process.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CLPB	Scaffold/PPI	no		ClpA/B, Ankyrin_rpt, AAA+_ATPase

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
left testis	1
right testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CLPB	205	ubiquitous	marker	sperm, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLPB	5,095

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CLPB	Q9H078	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
RIG-I signaling pathway	1	2407.4×	0.002	CLPB
granulocyte differentiation	1	1203.7×	0.002	CLPB
cellular response to heat	1	343.9×	0.004	CLPB
antiviral innate immune response	1	227.7×	0.004	CLPB

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CLPB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	CLPB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CLPB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.