Specific granule deficiency 1

Summary

Specific granule deficiency 1 (MONDO:0044207) is a disease caused by CEBPE (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CEBPE (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	specific granule deficiency 1
Mondo ID	MONDO:0044207
OMIM	245480
UMLS	C4551556
MedGen	1644049
GARD	0025882
Is cancer (heuristic)	no

Also known as: CEBPE specific granule deficiency · SGD1 · specific granule deficiency · specific granule deficiency 1 · specific granule deficiency caused by mutation in CEBPE

Data availability: 12 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 › specific granule deficiency › specific granule deficiency 1

Related subtypes (1): specific granule deficiency 2

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

12 retrieved; paginated sample, class counts are floors:

8 pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1705852	NM_001805.4(CEBPE):c.742_747del (p.Ser248_Arg249del)	CEBPE	Pathogenic	no assertion criteria provided
1705853	NM_001805.4(CEBPE):c.403C>T (p.Arg135Ter)	CEBPE	Pathogenic	criteria provided, single submitter
1705854	NM_001805.4(CEBPE):c.655_665del (p.Lys220fs)	CEBPE	Pathogenic	no assertion criteria provided
8854	NM_001805.4(CEBPE):c.249_253del (p.Asp84fs)	CEBPE	Pathogenic	no assertion criteria provided
8855	NM_001805.4(CEBPE):c.509dup (p.Ala171fs)	CEBPE	Pathogenic	no assertion criteria provided
369729	NM_001098426.2(SMARCD2):c.1181+1G>A	SMARCD2	Pathogenic	no assertion criteria provided
369730	NM_001098426.2(SMARCD2):c.414_438dup (p.Gln147delinsGluAspGlyArgTer)	SMARCD2	Pathogenic	no assertion criteria provided
369731	NM_001098426.2(SMARCD2):c.401+2T>C	SMARCD2	Pathogenic	no assertion criteria provided
982783	NM_001805.4(CEBPE):c.653T>C (p.Val218Ala)	CEBPE	Likely pathogenic	criteria provided, single submitter
714668	NM_001805.4(CEBPE):c.842G>A (p.Ser281Asn)	CEBPE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
530665	NM_001805.4(CEBPE):c.205C>T (p.Leu69Phe)	CEBPE	Uncertain significance	criteria provided, multiple submitters, no conflicts
640081	NM_001805.4(CEBPE):c.66G>T (p.Gly22=)	CEBPE	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 3 · 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
CEBPE	Strong	Autosomal recessive	specific granule deficiency 1	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEBPE	Orphanet:169142	Recurrent infections due to specific granule deficiency
CEBPE	Orphanet:566067	CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome
SMARCD2	Orphanet:169142	Recurrent infections due to specific granule deficiency

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
CEBPE	HGNC:1836	ENSG00000092067	Q15744	CCAAT/enhancer-binding protein epsilon	gencc,clinvar
SMARCD2	HGNC:11107	ENSG00000108604	Q92925	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEBPE	CCAAT/enhancer-binding protein epsilon	Transcriptional activator.
SMARCD2	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 2	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEBPE	Other/Unknown	no		bZIP, C/EBP_chordates, C/EBP
SMARCD2	Other/Unknown	no		SWIB_MDM2_domain, SWIB_domain, SMARCD2_SWIB_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bone element	1
bone marrow	1
trabecular bone tissue	1
endometrium epithelium	1
skin of abdomen	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEBPE	99	tissue_specific	marker	bone marrow, bone element, trabecular bone tissue
SMARCD2	251	ubiquitous	marker	skin of abdomen, skin of leg, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCD2	2,025
CEBPE	1,496

Intra-cohort edges

A	B	Sources
CEBPE	SMARCD2	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CEBPE	Q15744	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SMARCD2	Q92925	78.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. 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
Formation of the non-canonical BAF (ncBAF) complex	1	335.9×	0.018	SMARCD2
Formation of the polybromo-BAF (pBAF) complex	1	317.2×	0.018	SMARCD2
Formation of the embryonic stem cell BAF (esBAF) complex	1	300.5×	0.018	SMARCD2
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	228.4×	0.018	SMARCD2
Regulation of endogenous retroelements	1	184.2×	0.018	SMARCD2
Developmental Biology	2	14.5×	0.018	CEBPE, SMARCD2
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	150.3×	0.019	SMARCD2
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.019	SMARCD2
MITF-M-dependent gene expression	1	90.6×	0.024	SMARCD2
RMTs methylate histone arginines	1	73.2×	0.025	SMARCD2
Transcriptional regulation by RUNX1	1	73.2×	0.025	SMARCD2
Transcriptional regulation of granulopoiesis	1	62.8×	0.025	CEBPE
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	58.9×	0.025	SMARCD2
MITF-M-regulated melanocyte development	1	57.1×	0.025	SMARCD2
Chromatin organization	1	40.8×	0.032	SMARCD2
Chromatin modifying enzymes	1	36.1×	0.033	SMARCD2
Epigenetic regulation of gene expression	1	35.7×	0.033	SMARCD2
RNA Polymerase II Transcription	1	11.3×	0.096	SMARCD2
Gene expression (Transcription)	1	8.9×	0.115	SMARCD2
Generic Transcription Pathway	1	7.5×	0.128	SMARCD2

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
granulocyte differentiation	1	601.9×	0.010	CEBPE
nucleosome disassembly	1	401.2×	0.010	SMARCD2
integrated stress response signaling	1	351.1×	0.010	CEBPE
regulation of G0 to G1 transition	1	337.0×	0.010	SMARCD2
myeloid cell differentiation	1	324.1×	0.010	CEBPE
regulation of nucleotide-excision repair	1	300.9×	0.010	SMARCD2
regulation of mitotic metaphase/anaphase transition	1	247.8×	0.010	SMARCD2
macrophage differentiation	1	234.1×	0.010	CEBPE
positive regulation of T cell differentiation	1	227.7×	0.010	SMARCD2
positive regulation of myoblast differentiation	1	183.2×	0.011	SMARCD2
positive regulation of double-strand break repair	1	172.0×	0.011	SMARCD2
regulation of G1/S transition of mitotic cell cycle	1	153.2×	0.011	SMARCD2
positive regulation of cell differentiation	1	133.8×	0.011	SMARCD2
regulation of transcription by RNA polymerase II	2	11.7×	0.011	CEBPE, SMARCD2
phagocytosis	1	120.4×	0.011	CEBPE
DNA-templated transcription	1	112.3×	0.011	CEBPE
defense response	1	108.0×	0.011	CEBPE
cellular response to lipopolysaccharide	1	49.0×	0.024	CEBPE
chromatin remodeling	1	36.5×	0.030	SMARCD2
positive regulation of gene expression	1	19.4×	0.054	CEBPE
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	CEBPE

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMARCD2	1	2
CEBPE	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SMARCD2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCD2	7	Binding:7

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

1 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)
MOLIBRESIB	2	SMARCD2

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	1	SMARCD2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CEBPE

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)
CEBPE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.