SMARCD3

Summary

SMARCD3 (SWI/SNF related BAF chromatin remodeling complex subunit D3, HGNC:11108) is a protein-coding gene on chromosome 7q36.1, encoding SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 (Q6STE5). 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. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined.

Source: NCBI Gene 6604 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_001003801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11108
Approved symbol	SMARCD3
Name	SWI/SNF related BAF chromatin remodeling complex subunit D3
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	BAF60C, Rsc6p, CRACD3
Ensembl gene	ENSG00000082014
Ensembl biotype	protein_coding
OMIM	601737
Entrez	6604

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 5 retained_intron, 4 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000262188, ENST00000356800, ENST00000392811, ENST00000460431, ENST00000469154, ENST00000470588, ENST00000472103, ENST00000472789, ENST00000472988, ENST00000477169, ENST00000485592, ENST00000485610, ENST00000489503, ENST00000491651, ENST00000496530

RefSeq mRNA: 3 — MANE Select: NM_001003801 NM_001003801, NM_001003802, NM_003078

CCDS: CCDS34780, CCDS5924

Canonical transcript exons

ENST00000262188 — 13 exons

Exon	Start	End
ENSE00000730176	151240425	151240522
ENSE00001475292	151248485	151248694
ENSE00003474281	151239624	151239746
ENSE00003477854	151242481	151242603
ENSE00003481026	151243659	151243701
ENSE00003520756	151245460	151245671
ENSE00003534981	151241492	151241653
ENSE00003598896	151240112	151240247
ENSE00003599198	151242137	151242232
ENSE00003632745	151239396	151239497
ENSE00003684083	151241877	151241978
ENSE00003788514	151242721	151242843
ENSE00003903706	151238780	151239156

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0885 / max 296.9925, expressed in 1671 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86893	8.0600	1472
86889	3.7261	1072
86891	2.2328	864
86890	0.4083	170
86887	0.2676	124
86892	0.1732	48
86888	0.1527	57
86894	0.0678	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.06	gold quality
nucleus accumbens	UBERON:0001882	98.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.26	gold quality
right atrium auricular region	UBERON:0006631	98.22	gold quality
adenohypophysis	UBERON:0002196	98.11	gold quality
cerebellar hemisphere	UBERON:0002245	98.06	gold quality
right frontal lobe	UBERON:0002810	98.05	gold quality
apex of heart	UBERON:0002098	97.99	gold quality
anterior cingulate cortex	UBERON:0009835	97.99	gold quality
cerebellar cortex	UBERON:0002129	97.98	gold quality
cingulate cortex	UBERON:0003027	97.98	gold quality
caudate nucleus	UBERON:0001873	97.90	gold quality
cortical plate	UBERON:0005343	97.88	gold quality
cardiac atrium	UBERON:0002081	97.84	gold quality
amygdala	UBERON:0001876	97.77	gold quality
right coronary artery	UBERON:0001625	97.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.59	gold quality
putamen	UBERON:0001874	97.58	gold quality
right ovary	UBERON:0002118	97.55	gold quality
right adrenal gland cortex	UBERON:0035827	97.41	gold quality
right adrenal gland	UBERON:0001233	97.40	gold quality
gastrocnemius	UBERON:0001388	97.40	gold quality
pituitary gland	UBERON:0000007	97.28	gold quality
ascending aorta	UBERON:0001496	97.17	gold quality
thoracic aorta	UBERON:0001515	97.13	gold quality
popliteal artery	UBERON:0002250	97.12	gold quality
tibial artery	UBERON:0007610	97.12	gold quality
left adrenal gland cortex	UBERON:0035825	97.12	gold quality
aorta	UBERON:0000947	97.05	gold quality
descending thoracic aorta	UBERON:0002345	96.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	33.97
E-ANND-3	yes	10.08

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
MYOG	Activation
SGCA	Activation

Upstream regulators (CollecTRI, top): SMAD2, TP63

miRNA regulators (miRDB)

7 targeting SMARCD3, 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-4731-5P	99.89	67.23	2537
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-5586-5P	96.29	68.02	685
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675

Literature-anchored findings (GeneRIF, showing 14)

• BAF60c represents a new coregulator that constitutes an important anchoring point by which the SWI/SNF complex is recruited to nuclear receptors and other transcription factors (PMID:14701856)
• Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300. (PMID:16687403)
• Baf60c is re-expressed in the Muller glial cells that re-enter the cell cycle after neurotoxic damage (PMID:18816825)
• GTNB directs cardiogenesis from human embryonic stem cells and induces correct cardiac development. (PMID:21694703)
• BAF60c phosphorylation on a conserved threonine is the signal that promotes incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which remodels the chromatin & activates transcription of MyoD-target genes. (PMID:22068056)
• Data show a combination of only five genes (-BCL6, T (BRACHYURY), c-MYC, MITF and BAF60C (SMARCD3) rapidly and efficiently convert postnatal chorion and decidual cells into chondrocytes. (PMID:22833560)
• BAF60c promotes lipogenesis in vivo and increases triglyceride levels, demonstrating its role in metabolic adaption to activate the lipogenic program in response to feeding and insulin. (PMID:23219531)
• Deptor is induced by the Baf60c-Six4 transcriptional complex and mediates activation of Akt and glycolytic metabolism by Baf60c in a cell-autonomous manner (PMID:23563706)
• Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3 -induced epithelial-mesenchymal transition. Thus, Smarcd3 epigenetically regulates epithelial-mesenchymal transition by activating WNT signaling pathways. (PMID:23716599)
• Data show that the combination of GATA binding protein 4 (Gata4), T-box transcription factor 5 (Tbx5) and BRG1-associated factor 60C protein (Baf60c) is sufficient for inducing adipose tissue-derived mesenchymal stem cells (ADMSCs) to form cardiomyocytes. (PMID:26071180)
• SMARCD3 is a potential prognostic marker and therapeutic target in CAFs. (PMID:33125346)
• BAF60c prevents abdominal aortic aneurysm formation through epigenetic control of vascular smooth muscle cell homeostasis. (PMID:36066968)
• Smarcd3 is an epigenetic modulator of the metabolic landscape in pancreatic ductal adenocarcinoma. (PMID:36653361)
• Myofiber Baf60c controls muscle regeneration by modulating Dkk3-mediated paracrine signaling. (PMID:37284884)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	smarcd3b	ENSDARG00000019969
danio_rerio	smarcd3a	ENSDARG00000038786
mus_musculus	Smarcd3	ENSMUSG00000028949
rattus_norvegicus	Smarcd3	ENSRNOG00000010077
drosophila_melanogaster	Non2	FBGN0035370
caenorhabditis_elegans		WBGENE00010523
caenorhabditis_elegans	swsn-2.2	WBGENE00015971
caenorhabditis_elegans		WBGENE00020779
caenorhabditis_elegans		WBGENE00044072

Paralogs (2): SMARCD1 (ENSG00000066117), SMARCD2 (ENSG00000108604)

Protein

Protein identifiers

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 — Q6STE5 (reviewed: Q6STE5)

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

All UniProt accessions (5): Q6STE5, A0A090N8Z9, C9JYI7, F8WBJ3, H7C4E9

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. Stimulates nuclear receptor mediated transcription. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.

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/BAF190A, 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 neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin. May be a 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. Interacts with SMARCA4/BRG1/BAF190A. Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A. The precise distribution of the related SMARCD1, SMARCD2 and SMARCD3 proteins among these and other SWI/SNF nucleosome-remodeling complexes is not fully known. May allow recruitment of SWI/SNF containing complexes specifically to promoters where these factors are located. Also interacts with several nuclear receptors including PPARG/NR1C3, RXRA/NR1F1, ESR1, NR5A1, NR5A2/LRH1 and other transcriptional activators including the HLH protein SREBF1/SREBP1 and the homeobox protein PBX1. Interacts with PRDM1/BLIMP1.

Subcellular location. Nucleus.

Tissue specificity. Isoform 2 and isoform 1 are expressed in brain, heart, kidney, placenta, prostate, salivary gland, spleen, testis, thyroid, trachea and uterus. Isoform 1 is also expressed in skeletal muscle and adipose tissue.

Similarity. Belongs to the SMARCD family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6STE5-1	1, BAF60C2	yes
Q6STE5-2	2, BAF60C1

RefSeq proteins (3): NP_001003801, NP_001003802, NP_003069 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003121	SWIB_MDM2_domain	Domain
IPR019835	SWIB_domain	Domain
IPR036885	SWIB_MDM2_dom_sf	Homologous_superfamily
IPR038043	SMARCD3_SWIB_dom	Domain

Pfam: PF02201

UniProt features (12 total): sequence conflict 3, modified residue 2, initiator methionine 1, chain 1, domain 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6STE5-F1	80.99	0.61

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 (2): 2, 178

Function

Pathways and Gene Ontology

Reactome pathways

41 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-1989781	PPARA activates gene expression
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707616	Heme signaling
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-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression
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-1368082
R-HSA-1430728	Metabolism
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-400253
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 324 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE

GO Biological Process (22): positive regulation of neuroblast proliferation (GO:0002052), secondary heart field specification (GO:0003139), cardiac right ventricle formation (GO:0003219), neural retina development (GO:0003407), nucleosome disassembly (GO:0006337), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), regulation of mitotic metaphase/anaphase transition (GO:0030071), muscle cell differentiation (GO:0042692), positive regulation of T cell differentiation (GO:0045582), positive regulation of cell differentiation (GO:0045597), positive regulation of myoblast differentiation (GO:0045663), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of smooth muscle cell differentiation (GO:0051152), 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), heart morphogenesis (GO:0003007), chromatin organization (GO:0006325)

GO Molecular Function (8): transcription coregulator binding (GO:0001221), chromatin binding (GO:0003682), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), signaling receptor binding (GO:0005102), nuclear receptor binding (GO:0016922), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), SWI/SNF complex (GO:0016514), brahma complex (GO:0035060), npBAF complex (GO:0071564), nBAF complex (GO:0071565)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	4
Circadian clock	3
Regulation of lipid metabolism by PPARalpha	1
Mitochondrial biogenesis	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Chromatin modifying enzymes	1
Adipogenesis	1
Metabolism of lipids	1
Transcriptional regulation by RUNX1	1
Cellular response to chemical stress	1
Cellular responses to stress	1
MITF-M-dependent gene expression	1
Regulation of endogenous retroelements	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
cell differentiation	2
transcription factor binding	2
binding	2
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
heart field specification	1
cardiac ventricle formation	1
cardiac right ventricle morphogenesis	1
anatomical structure development	1
retina development in camera-type eye	1
protein-DNA complex disassembly	1
nucleosome organization	1
chromatin organization	1
transcription by RNA polymerase II	1
system development	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of metaphase/anaphase transition of cell cycle	1
muscle structure development	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	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
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1

Protein interactions and networks

STRING

1826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMARCD3	SMARCA4	P51532	997
SMARCD3	SMARCC2	Q8TAQ2	989
SMARCD3	MYOD1	P15172	986
SMARCD3	GATA4	P43694	974
SMARCD3	SMARCC1	Q92922	968
SMARCD3	ARID1A	O14497	961
SMARCD3	TBX5	Q99593	959
SMARCD3	DPF3	Q92784	936
SMARCD3	NKX2-5	P52952	916
SMARCD3	SMARCB1	Q12824	911
SMARCD3	PBRM1	Q86U86	900
SMARCD3	SMARCA2	P51531	898
SMARCD3	SMARCE1	Q969G3	897
SMARCD3	BANF1	O75531	882
SMARCD3	USF1	P22415	813

IntAct

78 interactions, top by confidence:

A	B	Type	Score
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
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
RELB	NFKBIE	psi-mi:“MI:0914”(association)	0.670
SMARCD3	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640

BioGRID (187): SMARCD3 (Affinity Capture-MS), SMARCD3 (Affinity Capture-MS), SMARCD3 (Affinity Capture-MS), SMARCD3 (Affinity Capture-MS), SMARCD3 (Affinity Capture-MS), SMARCD3 (Affinity Capture-MS), ACTL6A (Co-fractionation), ARID1A (Co-fractionation), ARID1B (Co-fractionation), BCL7A (Co-fractionation), BCL7B (Co-fractionation), BCL7C (Co-fractionation), DPF2 (Co-fractionation), HMGB1 (Co-fractionation), POLR2D (Co-fractionation)

ESM2 similar proteins: A0JP85, A1A5H6, A2RRV3, A5YKK6, B5DF93, E1BJD1, O02101, O14964, O35954, O54772, O75061, O95155, P97496, Q08BU1, Q09646, Q0V8S0, Q27974, Q2TBN1, Q3TC46, Q5BKE0, Q5HZZ6, Q5R8Q4, Q5U2N3, Q60520, Q61010, Q61466, Q6DD30, Q6EU10, Q6NYT1, Q6NZA9, Q6P9Z1, Q6STE5, Q6ZQ08, Q80TZ3, Q86TB9, Q86Y01, Q92922, Q92925, Q960E8, Q960X8

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

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
MYOD1	up-regulates	SMARCD3	binding
SMARCD3	“up-regulates quantity by expression”	MYOG	“transcriptional regulation”
MAPK14	“up-regulates activity”	SMARCD3	phosphorylation
PHF7	“form complex”	SMARCD3	binding
SMARCD3	“form complex”	“SWI/SNF ACTL6A-ARID1A-SMARCA2 variant”	binding
SMARCD3	“form complex”	“Neural progenitor-specific SWI/SNF”	binding
SMARCD3	“form complex”	“Muscle cell-specific SWI/SNF ARID1A variant”	binding
SMARCD3	“form complex”	“Muscle cell-specific SWI/SNF ARID1B variant”	binding
SMARCD3	“form complex”	“Muscle cell-specific SWI/SNF SMARCA4 variant”	binding
SMARCD3	“up-regulates activity”	MYOD1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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	15	158.6×	3e-30
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	16	121.8×	2e-29
Formation of the embryonic stem cell BAF (esBAF) complex	11	110.2×	2e-19
Formation of the non-canonical BAF (ncBAF) complex	9	100.8×	2e-15
Formation of the polybromo-BAF (pBAF) complex	9	95.2×	4e-15
Regulation of endogenous retroelements	12	73.7×	2e-18
Regulation of MITF-M-dependent genes involved in pigmentation	16	70.8×	1e-24
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	9	45.1×	9e-12

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	14	138.8×	2e-25
regulation of nucleotide-excision repair	14	123.9×	8e-25
regulation of mitotic metaphase/anaphase transition	14	102.0×	2e-23
positive regulation of double-strand break repair	14	70.8×	6e-21
nucleosome disassembly	6	70.8×	6e-09
regulation of G1/S transition of mitotic cell cycle	14	63.1×	3e-20
positive regulation of T cell differentiation	9	60.3×	1e-12
positive regulation of myoblast differentiation	11	59.3×	2e-15

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2244 predictions. Top by Δscore:

Variant	Effect	Δscore
7:151239391:CATA:C	donor_loss	1.0000
7:151239392:ATAC:A	donor_loss	1.0000
7:151239393:TA:T	donor_loss	1.0000
7:151239394:A:C	donor_loss	1.0000
7:151239395:C:CA	donor_loss	1.0000
7:151239395:CCTTG:C	donor_gain	1.0000
7:151239494:TCAC:T	acceptor_gain	1.0000
7:151239495:CAC:C	acceptor_gain	1.0000
7:151239495:CACC:C	acceptor_gain	1.0000
7:151239498:C:CC	acceptor_gain	1.0000
7:151239569:T:A	donor_gain	1.0000
7:151239573:T:A	donor_gain	1.0000
7:151239601:ACTC:A	donor_gain	1.0000
7:151239602:CTCC:C	donor_gain	1.0000
7:151239604:C:CA	donor_gain	1.0000
7:151239605:C:A	donor_gain	1.0000
7:151239614:C:CA	donor_gain	1.0000
7:151239742:TGGAT:T	acceptor_gain	1.0000
7:151239743:GGAT:G	acceptor_gain	1.0000
7:151239744:GAT:G	acceptor_gain	1.0000
7:151239744:GATCT:G	acceptor_loss	1.0000
7:151239745:ATCTG:A	acceptor_loss	1.0000
7:151239747:C:CC	acceptor_gain	1.0000
7:151239748:T:A	acceptor_loss	1.0000
7:151240115:A:AC	donor_gain	1.0000
7:151240116:C:CC	donor_gain	1.0000
7:151240116:CTGT:C	donor_gain	1.0000
7:151240131:ATCT:A	donor_gain	1.0000
7:151241821:AGC:A	donor_gain	1.0000
7:151241974:TGCCA:T	acceptor_gain	1.0000

AlphaMissense

3185 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:151239703:C:A	R406M	1.000
7:151239715:A:G	L402P	1.000
7:151239724:A:C	I399R	1.000
7:151239724:A:T	I399K	1.000
7:151239728:A:G	S398P	1.000
7:151240122:A:G	L388P	1.000
7:151240206:A:T	I360N	1.000
7:151240428:A:C	I345S	1.000
7:151240428:A:G	I345T	1.000
7:151240428:A:T	I345N	1.000
7:151240435:G:C	H343D	1.000
7:151240440:A:C	I341S	1.000
7:151240440:A:G	I341T	1.000
7:151240440:A:T	I341N	1.000
7:151240446:A:T	I339N	1.000
7:151240449:G:T	P338Q	1.000
7:151240464:A:G	L333P	1.000
7:151240476:A:G	L329P	1.000
7:151241517:A:T	I305N	1.000
7:151241544:A:G	L296P	1.000
7:151241563:A:C	Y290D	1.000
7:151241569:A:G	W288R	1.000
7:151241569:A:T	W288R	1.000
7:151241571:A:G	L287P	1.000
7:151241625:A:G	L269P	1.000
7:151241893:A:G	L254P	1.000
7:151241893:A:T	L254H	1.000
7:151241896:A:G	L253P	1.000
7:151241899:A:G	L252P	1.000
7:151241904:G:C	C250W	1.000

dbSNP variants (sampled 300 via entrez): RS1000075118 (7:151272836 C>T), RS1000121899 (7:151259183 C>T), RS1000356845 (7:151242391 C>G,T), RS1000389532 (7:151242583 G>A,C,T), RS1000400016 (7:151245725 C>G,T), RS1000513553 (7:151259467 T>C), RS1000710301 (7:151275549 G>A), RS1000723609 (7:151241272 TG>T,TGG), RS1000784577 (7:151264832 G>A), RS1000875590 (7:151246166 C>T), RS1000958154 (7:151269737 C>A,T), RS1001172453 (7:151263366 A>C,G), RS1001309172 (7:151257787 G>A), RS1001317271 (7:151252409 C>T), RS1001349318 (7:151244335 T>A,C)

Disease associations

OMIM: gene MIM:601737 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001848_161	IgG glycosylation	2.000000e-10
GCST001848_453	IgG glycosylation	2.000000e-09
GCST001848_557	IgG glycosylation	1.000000e-09
GCST001848_60	IgG glycosylation	7.000000e-06
GCST001848_603	IgG glycosylation	6.000000e-10
GCST003476_9	Eyebrow thickness	7.000000e-06
GCST004028_4	Immunoglobulin light chain (AL) amyloidosis	5.000000e-08
GCST004483_3	Multiple myeloma	1.000000e-08
GCST006979_221	Heel bone mineral density	6.000000e-15
GCST012396_9	Multiple myeloma	3.000000e-10
GCST90002383_442	Hematocrit	2.000000e-14
GCST90002384_167	Hemoglobin	7.000000e-13
GCST90002403_595	Red blood cell count	5.000000e-16

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement
EFO:0009270	heel bone mineral density
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Cyclosporine	decreases expression, decreases methylation	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases methylation	1
methylselenic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Selenium	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression, increases methylation	1
Asbestos, Crocidolite	affects expression	1
Particulate Matter	increases abundance, decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8PR	Abcam HCT 116 SMARCD3 KO	Cancer cell line	Male
CVCL_B9BP	Abcam MCF-7 SMARCD3 KO	Cancer cell line	Female
CVCL_B9S7	Abcam A-549 SMARCD3 KO	Cancer cell line	Male
CVCL_TP62	HAP1 SMARCD3 (-) 1	Cancer cell line	Male
CVCL_TP63	HAP1 SMARCD3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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