SMARCD2

Summary

SMARCD2 (SWI/SNF related BAF chromatin remodeling complex subunit D2, HGNC:11107) is a protein-coding gene on chromosome 17q23.3, encoding SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 2 (Q92925). Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6603 — RefSeq curated summary.

At a glance

• Gene–disease (curated): specific granule deficiency 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 360 total — 20 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001098426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11107
Approved symbol	SMARCD2
Name	SWI/SNF related BAF chromatin remodeling complex subunit D2
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	BAF60B, Rsc6p, CRACD2, PRO2451
Ensembl gene	ENSG00000108604
Ensembl biotype	protein_coding
OMIM	601736
Entrez	6603

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 17 retained_intron, 16 protein_coding, 3 nonsense_mediated_decay

ENST00000225742, ENST00000323347, ENST00000448276, ENST00000450364, ENST00000577686, ENST00000577990, ENST00000580054, ENST00000581832, ENST00000584400, ENST00000584483, ENST00000697953, ENST00000698013, ENST00000698014, ENST00000698015, ENST00000698016, ENST00000698017, ENST00000698018, ENST00000698019, ENST00000698020, ENST00000698021, ENST00000698022, ENST00000698023, ENST00000698024, ENST00000698025, ENST00000698026, ENST00000698027, ENST00000698028, ENST00000698029, ENST00000869923, ENST00000869924, ENST00000934855, ENST00000934856, ENST00000934857, ENST00000934858, ENST00000934859, ENST00000952069

RefSeq mRNA: 3 — MANE Select: NM_001098426 NM_001098426, NM_001330439, NM_001330440

CCDS: CCDS45756, CCDS82187, CCDS82188

Canonical transcript exons

ENST00000448276 — 13 exons

Exon	Start	End
ENSE00000742162	63833069	63833170
ENSE00000742172	63833587	63833722
ENSE00001619276	63833298	63833420
ENSE00001673014	63842459	63842685
ENSE00003463372	63834167	63834328
ENSE00003548679	63835412	63835567
ENSE00003572901	63834705	63834800
ENSE00003580643	63837441	63837625
ENSE00003597961	63833909	63834006
ENSE00003627811	63834474	63834575
ENSE00003649537	63836922	63837044
ENSE00003651225	63837195	63837237
ENSE00003738977	63832081	63832991

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 97.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.4131 / max 251.9134, expressed in 1820 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167495	18.8116	1778
167499	10.8288	1767
167494	2.7095	1107
167496	1.4040	821
167498	1.3612	889
167492	0.6069	256
167491	0.3676	160
167497	0.3235	152

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	97.68	gold quality
skin of leg	UBERON:0001511	97.64	gold quality
endometrium epithelium	UBERON:0004811	97.21	gold quality
body of pancreas	UBERON:0001150	96.90	gold quality
mucosa of stomach	UBERON:0001199	96.69	gold quality
lower esophagus mucosa	UBERON:0035834	96.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.59	gold quality
body of stomach	UBERON:0001161	96.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.57	gold quality
left uterine tube	UBERON:0001303	96.56	gold quality
minor salivary gland	UBERON:0001830	96.56	gold quality
lower esophagus	UBERON:0013473	96.56	gold quality
cerebellar hemisphere	UBERON:0002245	96.54	gold quality
ectocervix	UBERON:0012249	96.54	gold quality
tibial nerve	UBERON:0001323	96.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.46	gold quality
cerebellar cortex	UBERON:0002129	96.43	gold quality
granulocyte	CL:0000094	96.38	gold quality
endocervix	UBERON:0000458	96.19	gold quality
right adrenal gland cortex	UBERON:0035827	96.16	gold quality
right ovary	UBERON:0002118	96.12	gold quality
right adrenal gland	UBERON:0001233	96.06	gold quality
right lung	UBERON:0002167	95.98	gold quality
esophagus	UBERON:0001043	95.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.94	gold quality
right coronary artery	UBERON:0001625	95.90	gold quality
vagina	UBERON:0000996	95.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.76	gold quality
mucosa of transverse colon	UBERON:0004991	95.70	gold quality
esophagus mucosa	UBERON:0002469	95.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting SMARCD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 6)

• the Rac- and Unkempt-dependent process leading to BAF60b ubiquitination takes place in the nuclear compartment (PMID:20148946)
• the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia, was investigated. (PMID:26571505)
• Data show that both CEBPE and SMARCD2 loss-of-function mutations identified in patients with neutrophil-specific granule deficiency (SGD) abolish the interaction with SWI/SNF and secondary granule gene expression, thus providing a molecular basis for this disease. (PMID:28369034)
• Defective expression of SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2) leads to transcriptional and chromatin changes in acute myeloid leukemia (AML) promyelocytic cells, suggesting SMARCD2 is a key factor controlling myelopoiesis and is a potential tumor suppressor in leukemia. (PMID:28369036)
• Novel Frameshift Autosomal Recessive Loss-of-Function Mutation in SMARCD2 Encoding a Chromatin Remodeling Factor Mediates Granulopoiesis. (PMID:33025377)
• Defective neutrophil development and specific granule deficiency caused by a homozygous splice-site mutation in SMARCD2. (PMID:33279574)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	smarcd2	ENSDARG00000088877
mus_musculus	Smarcd2	ENSMUSG00000078619
rattus_norvegicus	Smarcd2	ENSRNOG00000010557
drosophila_melanogaster	Non2	FBGN0035370
caenorhabditis_elegans		WBGENE00010523
caenorhabditis_elegans	swsn-2.2	WBGENE00015971
caenorhabditis_elegans		WBGENE00020779
caenorhabditis_elegans		WBGENE00044072

Paralogs (2): SMARCD1 (ENSG00000066117), SMARCD3 (ENSG00000082014)

Protein

Protein identifiers

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 2 — Q92925 (reviewed: Q92925)

Alternative names: 60 kDa BRG-1/Brm-associated factor subunit B, BRG1-associated factor 60B

All UniProt accessions (10): Q92925, A0A8V8TLC9, A0A8V8TLF4, A0A8V8TLV3, A0A8V8TN45, J3KMX2, J3KT18, J3QQL7, J3QS33, J3QWB6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation.

Subunit / interactions. Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B), and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (ACTB). Interacts with UNKL. Interacts with CEBPE.

Subcellular location. Nucleus.

Tissue specificity. Isoform 2 is expressed in the pancreas.

Post-translational modifications. Ubiquitinated through a signaling process involving RAC1 and the RING finger protein UNKL.

Disease relevance. Specific granule deficiency 2 (SGD2) [MIM:617475] A form of specific granule deficiency, an autosomal recessive disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. SGD2 is due to defective neutrophil development. Bone marrow findings include hypercellularity, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. Some patients may have additional findings, including delayed development, mild dysmorphic features, and distal skeletal anomalies. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Produced by aberrant splicing sites.

Similarity. Belongs to the SMARCD family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q92925-1	1	yes
Q92925-2	2
Q92925-3	3

RefSeq proteins (3): NP_001091896, NP_001317368, NP_001317369 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003121	SWIB_MDM2_domain	Domain
IPR019835	SWIB_domain	Domain
IPR030090	SMARCD2_SWIB_dom	Domain
IPR036885	SWIB_MDM2_dom_sf	Homologous_superfamily

Pfam: PF02201

UniProt features (19 total): sequence conflict 8, modified residue 4, splice variant 3, chain 1, domain 1, region of interest 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92925-F1	78.38	0.58

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 81, 104, 203, 217, 226

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9933939	Formation of the polybromo-BAF (pBAF) complex
R-HSA-9933946	Formation of the embryonic stem cell BAF (esBAF) complex
R-HSA-9933947	Formation of the non-canonical BAF (ncBAF) complex
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)
R-HSA-1266738	Developmental Biology
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9842860	Regulation of endogenous retroelements
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 463 (showing top): MORF_MTA1, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, LFA1_Q6, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, MORF_HDAC1, MORF_RAD21, CTATGCA_MIR153, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION

GO Biological Process (13): nucleosome disassembly (GO:0006337), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), regulation of mitotic metaphase/anaphase transition (GO:0030071), positive regulation of T cell differentiation (GO:0045582), positive regulation of cell differentiation (GO:0045597), positive regulation of myoblast differentiation (GO:0045663), regulation of G0 to G1 transition (GO:0070316), regulation of G1/S transition of mitotic cell cycle (GO:2000045), positive regulation of double-strand break repair (GO:2000781), regulation of nucleotide-excision repair (GO:2000819), chromatin organization (GO:0006325), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (4): transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), protein binding (GO:0005515), nucleosomal DNA binding (GO:0031492)

GO Cellular Component (10): kinetochore (GO:0000776), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear matrix (GO:0016363), SWI/SNF complex (GO:0016514), RSC-type complex (GO:0016586), protein-containing complex (GO:0032991), brahma complex (GO:0035060), bBAF complex (GO:0140092)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	4
Gene expression (Transcription)	2
Chromatin modifying enzymes	1
Transcriptional regulation by RUNX1	1
MITF-M-dependent gene expression	1
Regulation of endogenous retroelements	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Developmental Biology	1
Epigenetic regulation of gene expression	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
SWI/SNF superfamily-type complex	4
cellular anatomical structure	3
regulation of DNA-templated transcription	2
regulation of mitotic cell cycle phase transition	2
nuclear lumen	2
protein-DNA complex disassembly	1
nucleosome organization	1
chromatin organization	1
transcription by RNA polymerase II	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of metaphase/anaphase transition of cell cycle	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
cell differentiation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
positive regulation of developmental process	1
myoblast differentiation	1
positive regulation of cell differentiation	1
regulation of myoblast differentiation	1
regulation of cell cycle process	1
G0 to G1 transition	1
G1/S transition of mitotic cell cycle	1
regulation of cell cycle G1/S phase transition	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
regulation of DNA repair	1
nucleotide-excision repair	1
cellular component organization	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription regulator activity	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
binding	1
chromatin DNA binding	1
nucleosome binding	1

Protein interactions and networks

STRING

1540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMARCD2	SMARCC1	Q92922	990
SMARCD2	SMARCC2	Q8TAQ2	990
SMARCD2	SMARCE1	Q969G3	952
SMARCD2	SMARCB1	Q12824	935
SMARCD2	SMARCA4	P51532	917
SMARCD2	NOM1	Q5C9Z4	895
SMARCD2	SMARCA2	P51531	870
SMARCD2	ACTL6A	O96019	816
SMARCD2	PBRM1	Q86U86	770
SMARCD2	PHF10	Q8WUB8	769
SMARCD2	DPF1	Q92782	764
SMARCD2	DPF3	Q92784	758
SMARCD2	DPF2	Q92785	751
SMARCD2	ARID1A	O14497	748
SMARCD2	ARID1B	Q8NFD5	743

IntAct

157 interactions, top by confidence:

A	B	Type	Score
SMARCA4	ARID1A	psi-mi:“MI:0914”(association)	0.940
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
NUP50	KPNA4	psi-mi:“MI:0914”(association)	0.830
SMARCC1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCC2	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SS18	ARID1A	psi-mi:“MI:0914”(association)	0.760
DPF2	ARID1A	psi-mi:“MI:0914”(association)	0.730
SMARCE1	SMARCA2	psi-mi:“MI:0914”(association)	0.730

BioGRID (328): NOTCH2NL (Two-hybrid), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), ACTL6A (Co-fractionation), ARID1A (Co-fractionation), ARID1B (Co-fractionation), BCL7A (Co-fractionation)

ESM2 similar proteins: A2WY46, A6BLW4, B8A9B2, G0SB31, G4MRQ6, G4N3L5, M2TF54, O54772, O65001, O70132, P17208, P20264, P20265, P20266, P20267, P21952, P25209, P31360, P31361, P53784, P56222, Q01851, Q02516, Q03052, Q0JGS5, Q13164, Q60764, Q60EQ4, Q63262, Q655V5, Q69J40, Q69TW5, Q6EU10, Q75IZ7, Q8L4B2, Q8LCG7, Q8LH59, Q8QZW2, Q92925, Q960X8

Diamond homologs: E1BJD1, O02101, O54772, Q09646, Q2TBN1, Q556Z0, Q61466, Q6P9Z1, Q6STE5, Q92925, Q96GM5, Q99JR8, Q9FMT4, Q9P7S3, Q9VYG2, O74503, Q05024, Q08747

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
SMARCD2	“form complex”	“SWI/SNF ACTL6A-ARID1A-SMARCA2 variant”	binding
SMARCD2	“form complex”	“SWI/SNF ACTL6B varian”	binding
SMARCD2	“form complex”	“Muscle cell-specific SWI/SNF ARID1A variant”	binding
SMARCD2	“form complex”	“Muscle cell-specific SWI/SNF ARID1B variant”	binding
SMARCD2	“form complex”	“Muscle cell-specific SWI/SNF SMARCA4 variant”	binding
SMARCD2	“form complex”	“Brain-specific SWI/SNF SMARCA2 variant”	binding
SMARCD2	“form complex”	“Brain-specific SWI/SNF SMARCA4 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the canonical BAF (cBAF) complex	16	96.7×	5e-29
Formation of the embryonic stem cell BAF (esBAF) complex	15	85.9×	1e-25
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	19	82.7×	5e-32
Formation of the polybromo-BAF (pBAF) complex	13	78.5×	2e-21
Formation of the non-canonical BAF (ncBAF) complex	12	76.8×	1e-19
Regulation of endogenous retroelements	14	49.1×	3e-19
Regulation of MITF-M-dependent genes involved in pigmentation	18	45.5×	5e-24
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	10	28.6×	6e-11

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	17	89.5×	4e-28
regulation of nucleotide-excision repair	17	79.9×	4e-27
regulation of mitotic metaphase/anaphase transition	17	65.8×	3e-25
nucleosome disassembly	8	50.1×	1e-10
positive regulation of T cell differentiation	13	46.3×	6e-17
positive regulation of double-strand break repair	17	45.7×	3e-22
regulation of G1/S transition of mitotic cell cycle	17	40.7×	3e-21
positive regulation of myoblast differentiation	14	40.1×	3e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

360 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	7
Uncertain significance	127
Likely benign	177
Benign	7

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1073417	NM_001098426.2(SMARCD2):c.1480C>T (p.Arg494Ter)	Pathogenic
1252086	NM_001098426.2(SMARCD2):c.1429C>T (p.Arg477Ter)	Pathogenic
1382738	NM_001098426.2(SMARCD2):c.217C>T (p.Arg73Ter)	Pathogenic
1387690	NM_001098426.2(SMARCD2):c.1326_1329del (p.Thr443fs)	Pathogenic
1397694	NM_001098426.2(SMARCD2):c.1291C>T (p.Gln431Ter)	Pathogenic
1423127	NM_001098426.2(SMARCD2):c.1081del (p.Gln361fs)	Pathogenic
1451152	NM_001098426.2(SMARCD2):c.673dup (p.Asp225fs)	Pathogenic
1454359	NM_001098426.2(SMARCD2):c.1181+1del	Pathogenic
1686864	NM_001098426.2(SMARCD2):c.511C>T (p.Gln171Ter)	Pathogenic
1947736	NM_001098426.2(SMARCD2):c.737del (p.Lys246fs)	Pathogenic
2018047	NM_001098426.2(SMARCD2):c.442C>T (p.Arg148Ter)	Pathogenic
2123866	NM_001098426.2(SMARCD2):c.1374_1375del (p.Ser459fs)	Pathogenic
2748302	NM_001098426.2(SMARCD2):c.310C>T (p.Arg104Ter)	Pathogenic
2843787	NM_001098426.2(SMARCD2):c.572del (p.Lys191fs)	Pathogenic
3682590	NM_001098426.2(SMARCD2):c.1217dup (p.Tyr406Ter)	Pathogenic
369729	NM_001098426.2(SMARCD2):c.1181+1G>A	Pathogenic
369730	NM_001098426.2(SMARCD2):c.414_438dup (p.Gln147delinsGluAspGlyArgTer)	Pathogenic
369731	NM_001098426.2(SMARCD2):c.401+2T>C	Pathogenic
4704060	NM_001098426.2(SMARCD2):c.1099C>T (p.Arg367Ter)	Pathogenic
4730229	NM_001098426.2(SMARCD2):c.763_764insAGAAGATGTTGTTATACTGTATTATGGCTGATTTTCTTTTTAATATATTTAGCCAAGTGATGCACTTTATGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGA (p.Lys254_Ser255insLysLysMetLeuLeuTyrCysIleMetAlaAspPheLeuPheAsnIlePheSerGlnValMetHisPheMetXaaXaaXaaXaaLysLysLysLysLysLysLys)	Pathogenic
1325105	NM_001098426.2(SMARCD2):c.654del (p.Gly220fs)	Likely pathogenic
2050941	NM_001098426.2(SMARCD2):c.1440+1G>A	Likely pathogenic
2118895	NM_001098426.2(SMARCD2):c.217-1G>T	Likely pathogenic
2585369	NM_001098426.2(SMARCD2):c.391C>T (p.Gln131Ter)	Likely pathogenic
2767629	NM_001098426.2(SMARCD2):c.216+1G>C	Likely pathogenic
3650913	NM_001098426.2(SMARCD2):c.444+1G>A	Likely pathogenic
804421	NM_001098426.2(SMARCD2):c.568-1G>C	Likely pathogenic

SpliceAI

1789 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63833097:T:TA	donor_gain	1.0000
17:63833167:TGAT:T	acceptor_gain	1.0000
17:63833170:TCTG:T	acceptor_loss	1.0000
17:63833171:C:CC	acceptor_gain	1.0000
17:63833171:C:T	acceptor_loss	1.0000
17:63833172:T:A	acceptor_loss	1.0000
17:63833182:C:CT	acceptor_gain	1.0000
17:63833182:C:T	acceptor_gain	1.0000
17:63833329:T:TA	donor_gain	1.0000
17:63833421:C:CC	acceptor_gain	1.0000
17:63833582:CCCA:C	donor_loss	1.0000
17:63833583:CCACC:C	donor_loss	1.0000
17:63833584:CA:C	donor_loss	1.0000
17:63833586:C:CT	donor_loss	1.0000
17:63833609:T:TA	donor_gain	1.0000
17:63833718:CGACA:C	acceptor_gain	1.0000
17:63833719:GACA:G	acceptor_gain	1.0000
17:63833720:ACA:A	acceptor_gain	1.0000
17:63833720:ACACT:A	acceptor_loss	1.0000
17:63833721:CA:C	acceptor_gain	1.0000
17:63833721:CAC:C	acceptor_gain	1.0000
17:63833721:CACTG:C	acceptor_loss	1.0000
17:63833723:C:CC	acceptor_gain	1.0000
17:63833723:C:CG	acceptor_loss	1.0000
17:63833724:T:G	acceptor_loss	1.0000
17:63833727:A:T	acceptor_gain	1.0000
17:63833730:C:CT	acceptor_gain	1.0000
17:63833731:A:T	acceptor_gain	1.0000
17:63833733:C:CT	acceptor_gain	1.0000
17:63833735:C:CT	acceptor_gain	1.0000

AlphaMissense

3453 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63833302:A:G	L479P	1.000
17:63833359:A:G	F460S	1.000
17:63833365:A:G	L458P	1.000
17:63833370:G:C	F456L	1.000
17:63833370:G:T	F456L	1.000
17:63833372:A:G	F456L	1.000
17:63833376:T:A	R454S	1.000
17:63833376:T:G	R454S	1.000
17:63833377:C:A	R454I	1.000
17:63833377:C:G	R454T	1.000
17:63833385:C:A	K451N	1.000
17:63833385:C:G	K451N	1.000
17:63833389:A:G	L450P	1.000
17:63833398:A:T	I447N	1.000
17:63833402:A:G	S446P	1.000
17:63833407:A:T	I444N	1.000
17:63833597:A:G	L436P	1.000
17:63833681:A:T	I408N	1.000
17:63833684:T:C	D407G	1.000
17:63833912:A:C	I393S	1.000
17:63833912:A:G	I393T	1.000
17:63833912:A:T	I393N	1.000
17:63833919:G:C	H391D	1.000
17:63833924:A:C	I389S	1.000
17:63833924:A:G	I389T	1.000
17:63833924:A:T	I389N	1.000
17:63833930:A:T	I387N	1.000
17:63833948:A:G	L381P	1.000
17:63833960:A:G	L377P	1.000
17:63834219:A:G	L344P	1.000

dbSNP variants (sampled 300 via entrez): RS1000291856 (17:63841693 C>G,T), RS1000331225 (17:63844186 C>G,T), RS1000721192 (17:63842302 C>G,T), RS1000855851 (17:63834869 G>T), RS1001064483 (17:63842807 C>A,T), RS1001461166 (17:63836018 C>T), RS1002339021 (17:63841064 T>A), RS1002429741 (17:63831989 A>C,G), RS1002798480 (17:63840747 A>G), RS1002816334 (17:63838890 A>C,G), RS1003095840 (17:63839771 G>A), RS1003186590 (17:63843041 C>T), RS1003579004 (17:63832707 G>A,C,T), RS1003700248 (17:63836861 A>C,G), RS1004190063 (17:63842044 C>T)

Disease associations

OMIM: gene MIM:601736 | disease phenotypes: MIM:617475, MIM:245480

GenCC curated gene-disease

Disease	Classification	Inheritance
specific granule deficiency 2	Strong	Autosomal recessive
specific granule deficiency	Supportive	Autosomal recessive

Mondo (4): specific granule deficiency 2 (MONDO:0044208), autosomal recessive severe congenital neutropenia (MONDO:0028226), specific granule deficiency 1 (MONDO:0044207), specific granule deficiency (MONDO:0009506)

Orphanet (2): Recurrent infections due to specific granule deficiency (Orphanet:169142), Autosomal recessive severe congenital neutropenia (Orphanet:439849)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000403	Recurrent otitis media
HP:0000692	Tooth malposition
HP:0000698	Conical tooth
HP:0000705	Amelogenesis imperfecta
HP:0000938	Osteopenia
HP:0000956	Acanthosis nigricans
HP:0000974	Hyperextensible skin
HP:0001007	Hirsutism
HP:0001156	Brachydactyly
HP:0001263	Global developmental delay
HP:0001508	Failure to thrive
HP:0001522	Death in infancy
HP:0001808	Fragile nails
HP:0001852	Sandal gap
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001903	Anemia
HP:0002041	Intractable diarrhea
HP:0002164	Nail dysplasia
HP:0002718	Recurrent bacterial infections
HP:0002863	Myelodysplasia
HP:0003577	Congenital onset
HP:0003819	Death in childhood
HP:0006532	Recurrent pneumonia
HP:0012551	Absent neutrophil specific granules
HP:0020206	Simple ear

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90011898_51	Alanine aminotransferase levels	5.000000e-09

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562873	Specific Granule Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465341 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.26	IC50	550	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179063: Inhibition of SMARCD2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.5500	uM

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases methylation	3
Valproic Acid	affects expression, decreases methylation	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Copper	decreases expression, affects binding	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338442	Binding	Binding affinity to Smarcd2 (unknown origin) at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8AW	Ubigene A-549 SMARCD2 KO	Cancer cell line	Male
CVCL_TP61	HAP1 SMARCD2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.