Specific granule deficiency 2

Summary

Specific granule deficiency 2 (MONDO:0044208) is a disease caused by SMARCD2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SMARCD2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	specific granule deficiency 2
Mondo ID	MONDO:0044208
OMIM	617475
UMLS	C4479548
MedGen	1371952
GARD	0025883
Is cancer (heuristic)	no

Also known as: SGD2 · specific granule deficiency 2

Data availability: 12 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 › specific granule deficiency › specific granule deficiency 2

Related subtypes (1): specific granule deficiency 1

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:

5 pathogenic, 3 likely pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1252086	NM_001098426.2(SMARCD2):c.1429C>T (p.Arg477Ter)	SMARCD2	Pathogenic	criteria provided, single submitter
1686864	NM_001098426.2(SMARCD2):c.511C>T (p.Gln171Ter)	SMARCD2	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
996004	NM_001098426.2(SMARCD2):c.574C>T (p.Arg192Ter)	SMARCD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1325105	NM_001098426.2(SMARCD2):c.654del (p.Gly220fs)	SMARCD2	Likely pathogenic	criteria provided, single submitter
2585369	NM_001098426.2(SMARCD2):c.391C>T (p.Gln131Ter)	SMARCD2	Likely pathogenic	criteria provided, single submitter
804421	NM_001098426.2(SMARCD2):c.568-1G>C	SMARCD2	Likely pathogenic	criteria provided, single submitter
619069	NM_001098426.2(SMARCD2):c.93del (p.Ala32fs)	LOC130061409	Conflicting classifications of pathogenicity	no assertion criteria provided
1477193	NM_001098426.2(SMARCD2):c.922-3C>T	SMARCD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
790464	NM_001098426.2(SMARCD2):c.1545G>A (p.Val515=)	SMARCD2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
SMARCD2	Strong	Autosomal recessive	specific granule deficiency 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCD2	Orphanet:169142	Recurrent infections due to specific granule deficiency

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
SMARCD2	HGNC:11107	ENSG00000108604	Q92925	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCD2	Other/Unknown	no		SWIB_MDM2_domain, SWIB_domain, SMARCD2_SWIB_dom

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
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
SMARCD2	251	ubiquitous	marker	skin of abdomen, skin of leg, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCD2	2,025

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SMARCD2	Q92925	78.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 1 evidence-associated genes (1 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 1 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	671.8×	0.010	SMARCD2
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.010	SMARCD2
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.010	SMARCD2
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.010	SMARCD2
Regulation of endogenous retroelements	1	368.4×	0.010	SMARCD2
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.010	SMARCD2
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.010	SMARCD2
MITF-M-dependent gene expression	1	181.3×	0.013	SMARCD2
RMTs methylate histone arginines	1	146.4×	0.013	SMARCD2
Transcriptional regulation by RUNX1	1	146.4×	0.013	SMARCD2
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.014	SMARCD2
MITF-M-regulated melanocyte development	1	114.2×	0.014	SMARCD2
Chromatin organization	1	81.6×	0.018	SMARCD2
Chromatin modifying enzymes	1	72.3×	0.018	SMARCD2
Epigenetic regulation of gene expression	1	71.4×	0.018	SMARCD2
RNA Polymerase II Transcription	1	22.5×	0.053	SMARCD2
Gene expression (Transcription)	1	17.8×	0.063	SMARCD2
Generic Transcription Pathway	1	15.1×	0.069	SMARCD2
Developmental Biology	1	14.5×	0.069	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nucleosome disassembly	1	802.5×	0.004	SMARCD2
regulation of G0 to G1 transition	1	674.1×	0.004	SMARCD2
regulation of nucleotide-excision repair	1	601.9×	0.004	SMARCD2
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.004	SMARCD2
positive regulation of T cell differentiation	1	455.5×	0.004	SMARCD2
positive regulation of myoblast differentiation	1	366.4×	0.004	SMARCD2
positive regulation of double-strand break repair	1	343.9×	0.004	SMARCD2
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.004	SMARCD2
positive regulation of cell differentiation	1	267.5×	0.005	SMARCD2
chromatin remodeling	1	73.0×	0.015	SMARCD2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SMARCD2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
SMARCD2	1	2

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: 1; 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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.