Neutropenia, severe congenital, 10, autosomal recessive

Summary

Neutropenia, severe congenital, 10, autosomal recessive (MONDO:0957809) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neutropenia, severe congenital, 10, autosomal recessive
Mondo ID	MONDO:0957809
OMIM	620534
UMLS	C5882756
MedGen	1851433
GARD	0026875
Is cancer (heuristic)	no

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

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, 10, autosomal recessive

Related subtypes (7): autosomal dominant severe congenital neutropenia, X-linked severe congenital neutropenia, autosomal recessive severe congenital neutropenia, neutropenia, severe congenital, 9, autosomal dominant, neutropenia, severe congenital, 8, autosomal dominant, 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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2582671	NM_014230.4(SRP68):c.184+2T>C	GALR2	Pathogenic	no assertion criteria provided
2582672	NC_000017.11:g.(76070445_76072307)(76072518?)del	GALR2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
SRP68	Moderate	Autosomal recessive	neutropenia, severe congenital, 10, autosomal recessive	2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SRP68	HGNC:11302	ENSG00000167881	Q9UHB9	Signal recognition particle subunit SRP68	gencc
GALR2	HGNC:4133	ENSG00000182687	O43603	Galanin receptor type 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRP68	Signal recognition particle subunit SRP68	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).
GALR2	Galanin receptor type 2	Receptor for the hormone galanin and GALP.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

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

Family	Genes	Fold	FDR
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SRP68	Other/Unknown	no		SRP68, SRP68-RBD, SRP68_N_sf
GALR2	GPCR	yes		GPCR_Rhodpsn, Galanin_rcpt, GAL2_rcpt

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
deltoid	1
tibialis anterior	1
upper arm skin	1
lower esophagus mucosa	1
muscle layer of sigmoid colon	1
sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRP68	263	ubiquitous	marker	tibialis anterior, upper arm skin, deltoid
GALR2	84	tissue_specific	yes	muscle layer of sigmoid colon, sigmoid colon, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRP68	2,734
GALR2	565

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SRP68	Q9UHB9	9
GALR2	O43603	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SRP-dependent cotranslational protein targeting to membrane	1	50.1×	0.053	SRP68
Peptide ligand-binding receptors	1	37.1×	0.053	GALR2
Translation	1	31.0×	0.053	SRP68
G alpha (i) signalling events	1	19.5×	0.063	GALR2
Metabolism of proteins	1	6.2×	0.155	SRP68

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
galanin-activated signaling pathway	1	4213.0×	0.003	GALR2
SRP-dependent cotranslational protein targeting to membrane	1	1053.2×	0.007	SRP68
inositol phosphate metabolic process	1	495.6×	0.008	GALR2
phosphatidylinositol metabolic process	1	443.5×	0.008	GALR2
feeding behavior	1	271.8×	0.010	GALR2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	168.5×	0.014	GALR2
learning or memory	1	120.4×	0.017	GALR2
muscle contraction	1	104.0×	0.017	GALR2
phospholipase C-activating G protein-coupled receptor signaling pathway	1	65.8×	0.021	GALR2
neuron projection development	1	61.1×	0.021	GALR2
positive regulation of cytosolic calcium ion concentration	1	58.5×	0.021	GALR2
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	56.5×	0.021	GALR2
response to xenobiotic stimulus	1	34.5×	0.031	SRP68
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	GALR2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRP68	0	0
GALR2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GALR2	67	Binding:62, Functional:5
SRP68	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	GALR2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SRP68

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SRP68	1	—
GALR2	67	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.