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
• GTEx eGene: eQTL in 14 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.37 (moderately constrained)
• MANE Select transcript: NM_001003801
• Notable: 52 clinical variants but no curated precision-oncology (CIViC) evidence yet

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

MANE Select: ENST00000262188

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 4, TSL 3: 3, TSL 4: 1, TSL 5: 3

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.

Highest expression (Bgee): ganglionic eminence, nucleus accumbens, hemisphere of cerebellum, atrium auricular region, adenohypophysis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SMARCD3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	5.7e-17	+0.26	7:151256769:C:T
Testis	eqtl	6.7e-05	+0.22	7:151253854:G:A
Esophagus Gastroesophageal Junction	eqtl	1.3e-04	+0.30	7:151270387:A:G
Nerve Tibial	eqtl	1.8e-04	+0.19	7:151256119:C:A
Artery Tibial	eqtl	2.3e-03	+0.52	7:152025565:A:C
Heart Atrial Appendage	eqtl	2.9e-03	+0.37	7:151194935:C:G
Stomach	eqtl	8.2e-03	+0.22	7:151253854:G:A
Cells EBV-transformed lymphocytes	eqtl	8.8e-03	+0.35	7:151784304:C:T
Brain Cerebellum	eqtl	1.8e-02	+0.86	7:150839895:G:A
Colon Transverse	eqtl	1.9e-02	+0.13	7:151225220:T:C
Brain Spinal cord cervical c-1	eqtl	2.9e-02	-1.61	7:150387969:G:A
Heart Left Ventricle	eqtl	4.1e-02	-0.13	7:151588727:ACATGACT:A
Artery Coronary	eqtl	4.4e-02	+0.25	7:151329475:C:G
Thyroid	eqtl	4.9e-02	+0.17	7:151255684:G:A

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

showing 100 of 301 tissues 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
cerebellum	UBERON:0002037	96.97	gold quality
left coronary artery	UBERON:0001626	96.87	gold quality
left adrenal gland	UBERON:0001234	96.86	gold quality
right lobe of thyroid gland	UBERON:0001119	96.75	gold quality
muscle of leg	UBERON:0001383	96.67	gold quality
prefrontal cortex	UBERON:0000451	96.66	gold quality
coronary artery	UBERON:0001621	96.64	gold quality
adrenal cortex	UBERON:0001235	96.63	gold quality
left uterine tube	UBERON:0001303	96.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.56	gold quality
endocervix	UBERON:0000458	96.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.37	gold quality
left ovary	UBERON:0002119	96.28	gold quality
heart	UBERON:0000948	96.20	gold quality
hypothalamus	UBERON:0001898	96.15	gold quality
heart left ventricle	UBERON:0002084	96.13	gold quality
neocortex	UBERON:0001950	96.04	gold quality
left lobe of thyroid gland	UBERON:0001120	96.01	gold quality
monocyte	CL:0000576	95.99	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.94	gold quality
cardiac ventricle	UBERON:0002082	95.92	gold quality
forebrain	UBERON:0001890	95.86	gold quality
telencephalon	UBERON:0001893	95.81	gold quality
adrenal gland	UBERON:0002369	95.81	gold quality
muscle organ	UBERON:0001630	95.80	gold quality
skeletal muscle organ	UBERON:0014892	95.80	gold quality
nerve	UBERON:0001021	95.76	gold quality
tibial nerve	UBERON:0001323	95.76	gold quality
brain	UBERON:0000955	95.71	gold quality
frontal cortex	UBERON:0001870	95.71	gold quality
frontal lobe	UBERON:0016525	95.70	gold quality
central nervous system	UBERON:0001017	95.64	gold quality
temporal lobe	UBERON:0001871	95.61	gold quality
cerebral cortex	UBERON:0000956	95.53	gold quality
mononuclear cell	CL:0000842	95.34	gold quality
metanephros cortex	UBERON:0010533	95.27	gold quality
ventricular zone	UBERON:0003053	95.22	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.15	gold quality
body of uterus	UBERON:0009853	95.14	gold quality
adrenal tissue	UBERON:0018303	95.13	gold quality
leukocyte	CL:0000738	95.05	gold quality
Ammon’s horn	UBERON:0001954	94.96	gold quality
thyroid gland	UBERON:0002046	94.92	gold quality
lower esophagus	UBERON:0013473	94.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.86	gold quality
granulocyte	CL:0000094	94.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.74	gold quality
paraflocculus	UBERON:0005351	94.72	gold quality
middle frontal gyrus	UBERON:0002702	94.55	gold quality
mucosa of stomach	UBERON:0001199	94.50	gold quality
ectocervix	UBERON:0012249	94.42	gold quality
ovary	UBERON:0000992	94.40	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.24	gold quality
body of stomach	UBERON:0001161	94.01	gold quality
substantia nigra	UBERON:0002038	94.00	gold quality
upper lobe of left lung	UBERON:0008952	93.90	gold quality
vastus lateralis	UBERON:0001379	93.82	gold quality
triceps brachii	UBERON:0001509	93.74	gold quality
stromal cell of endometrium	CL:0002255	93.70	gold quality
skeletal muscle tissue	UBERON:0001134	93.69	gold quality
omental fat pad	UBERON:0010414	93.69	gold quality
peritoneum	UBERON:0002358	93.67	gold quality
quadriceps femoris	UBERON:0001377	93.63	gold quality
spinal cord	UBERON:0002240	93.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.55	gold quality
muscle tissue	UBERON:0002385	93.51	gold quality
gluteal muscle	UBERON:0002000	93.48	gold quality
midbrain	UBERON:0001891	93.36	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	120.5	medium
Caudate putamen	tissue	109.8
Nucleus accumbens	tissue	90.9
Postcentral gyrus	tissue	89.0
Hippocampus	tissue	75.7	not detected
Basal ganglia	tissue	74.4	low
Locus coeruleus	tissue	73.2
Putamen	tissue	69.2
Tongue	tissue	64.7
Frontal cortex	tissue	64.1
Ventral forebrain	tissue	56.2
Heart muscle	tissue	54.8	medium
Septum	tissue	50.4
Cerebral cortex	tissue	49.5	low
Motor cortex	tissue	49.5
Hippocampal formation	tissue	48.7
Thalamus	tissue	45.1
Prefrontal cortex	tissue	44.7
Pons	tissue	44.1
Midbrain	tissue	43.8
Temporal cortex	tissue	43.2
Somatosensory cortex	tissue	43.0
Insular cortex	tissue	43.0
Entorhinal cortex	tissue	42.9
Retrosplenial cortex	tissue	42.6
Pituitary gland	tissue	41.9
Retrosplenial and cingulate cortex	tissue	41.9
Hypothalamus	tissue	41.6
Amygdala	tissue	40.5
Superior colliculi	tissue	39.4
Occipital cortex	tissue	38.3
Substantia nigra	tissue	37.2
Periaqueductal gray	tissue	36.1
Medulla oblongata	tissue	35.8
Spinal cord	tissue	34.1
Ovary	tissue	31.8	medium
Olfactory bulb	tissue	30.4
Parathyroid gland	tissue	25.5	low
Choroid plexus	tissue	22.5
Seminal vesicle	tissue	21.9	not detected
Adrenal gland	tissue	20.2	not detected
Cerebellum	tissue	19.8	low
Corpus callosum	tissue	18.7
Vagina	tissue	17.9	not detected
Fallopian tube	tissue	17.9	medium
Cervix	tissue	15.6	not detected
Epididymis	tissue	13.8	low
Gallbladder	tissue	13.4	not detected
Prostate	tissue	13.1	not detected
Adipose tissue	tissue	12.6	low
Smooth muscle	tissue	12.5	medium
Breast	tissue	12.4	not detected
Urinary bladder	tissue	11.6	not detected
Testis	tissue	11.1	medium
Lung	tissue	10.5	not detected
Endometrium 1	tissue	10.0	medium
Retina	tissue	9.0
Pancreas	tissue	8.8	medium
Thyroid gland	tissue	8.5	medium
Esophagus	tissue	7.8	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Entorhinal gyrus (116.1), Stria terminalis, bed nucleus (114.1), Olfactory area (110.8), Perirhinal gyrus (110.3), Nucleus of the diagonal band (109.1).

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)

Targeting SMARCD3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

7 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.372, missense Z 3.79 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000262188 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:151,239,106–151,239,715	81 / 109.7	0.74	no
7:151,239,716–151,242,204	115 / 257.2	0.45	no
7:151,242,205–151,245,565	128 / 188.8	0.68	no
7:151,245,566–151,248,562	84 / 81.2	1.03	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914243) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 48 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart development	1
enlarged heart	1
thin ventricular wall	1
abnormal interventricular septum morphology	1
abnormal interatrial septum morphology	1
abnormal atrioventricular cushion morphology	1
absent vibrissae	1
postnatal growth retardation	1
hemorrhage	1
prenatal lethality	1
premature death	1
abnormal vibrissa morphology	1
abnormal muscle physiology	1
abnormal myocardial trabeculae morphology	1
thin myocardium	1
dilated heart left ventricle	1
increased cardiomyocyte apoptosis	1
prolonged QT interval	1
decreased cardiac output	1
thin myocardium compact layer	1
abnormal cardiac muscle relaxation	1
abnormal sarcomere morphology	1
abnormal Z line morphology	1
abnormal M line morphology	1
dilated heart	1

+23 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	E1BJD1	99.2%	Diamond
Schizosaccharomyces pombe 972h-	Q9P7S3	43.5%	Diamond
Arabidopsis thaliana	Q9FMT4	42.6%	Diamond
Dictyostelium discoideum	Q556Z0	36.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR3907	ncRNA	100500835
CRYGN	protein-coding	155051
WDR86	protein-coding	349136
NUB1	protein-coding	51667
H2BK1	protein-coding	114483833
ABCF2-H2BK1	protein-coding	114483834
DRC11L	protein-coding	392843
CHPF2	protein-coding	54480
MIR671	ncRNA	768213
ABCF2	protein-coding	10061
ASB10	protein-coding	136371
WDR86-AS1	ncRNA	100131176

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): A0A090N8Z9, C9JYI7, Q6STE5, 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH uncertain · IF enhanced

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)

Type	Positions
N-acetylalanine	2
Phosphoserine	178

Function

Pathways and Gene Ontology

Reactome pathways

11 curated (TAS) of 43; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

43 pathways:

ID	Pathway	Evidence
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)	curated
R-HSA-9707564	Cytoprotection by HMOX1	curated
R-HSA-9933946	Formation of the embryonic stem cell BAF (esBAF) complex	curated
R-HSA-9933947	Formation of the non-canonical BAF (ncBAF) complex	curated
R-HSA-9933939	Formation of the polybromo-BAF (pBAF) complex	curated
R-HSA-3214858	RMTs methylate histone arginines	curated
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	curated
R-HSA-400206	Regulation of lipid metabolism by PPARalpha	curated
R-HSA-9932451	SWI/SNF chromatin remodelers	curated
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis	curated
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation	curated
R-HSA-9932444	ATP-dependent chromatin remodelers	—
R-HSA-9843745	Adipogenesis	—
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression	electronic
R-HSA-9711123	Cellular response to chemical stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—
R-HSA-9909396	Circadian clock	—
R-HSA-1266738	Developmental Biology	—
R-HSA-212165	Epigenetic regulation of gene expression	—
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2	electronic
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	electronic
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9707616	Heme signaling	electronic
R-HSA-9856651	MITF-M-dependent gene expression	—
R-HSA-9730414	MITF-M-regulated melanocyte development	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-8957322	Metabolism of steroids	—
R-HSA-1592230	Mitochondrial biogenesis	—
R-HSA-1852241	Organelle biogenesis and maintenance	—
R-HSA-1989781	PPARA activates gene expression	electronic
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	electronic
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation	electronic
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)	—
R-HSA-9842860	Regulation of endogenous retroelements	—
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	electronic
R-HSA-9938024	Somatic hypermutation of immunoglobulin genes	electronic
R-HSA-8878171	Transcriptional regulation by RUNX1	—

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 (19): positive regulation of neuroblast proliferation (GO:0002052), neural retina development (GO:0003407), nucleosome disassembly (GO:0006337), chromatin remodeling (GO:0006338), DNA-templated transcription (GO:0006351), 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), 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), chromatin organization (GO:0006325)

GO Molecular Function (9): 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), ATP-dependent chromatin remodeler activity (GO:0140658)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), SWI/SNF complex (GO:0016514), npBAF complex (GO:0071564), nBAF complex (GO:0071565)

Reactome top-level categories

15 top-level categories:

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
ATP-dependent chromatin remodelers	1
Affinity selection of immunoglobulins	1

GO top-level categories

showing 60 of 63 GO namespaces:

Category	Terms
cellular anatomical structure	3
SWI/SNF superfamily-type complex	3
animal gross anatomical part developmental process	2
regulation of DNA-templated transcription	2
regulation of mitotic cell cycle phase transition	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
retina development in camera-type eye	1
protein-DNA complex disassembly	1
nucleosome organization	1
chromatin organization	1
gene expression	1
RNA biosynthetic process	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
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
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
smooth muscle cell differentiation	1
positive regulation of muscle cell differentiation	1
regulation of smooth muscle cell 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
transcription regulator activity	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
protein binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
DNA binding	1
chromatin remodeling	1
ATP-dependent activity, acting on DNA	1
chromosome	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 35 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
chromatin remodeling	BP	direct assay
neural retina development	BP	expression pattern
nucleosome disassembly	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of neuroblast proliferation	BP	direct assay
regulation of transcription by RNA polymerase II	BP	mutant phenotype
SWI/SNF complex	CC	direct assay
chromatin	CC	direct assay
cytoplasm	CC	direct assay
npBAF complex	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
DNA-binding transcription factor binding	MF	physical interaction
nuclear receptor binding	MF	physical interaction
signaling receptor binding	MF	physical interaction
transcription coactivator activity	MF	mutant phenotype
transcription coregulator binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,310 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMARCD3	SMARCC2	Q8TAQ2	898
SMARCD3	TBX5	Q99593	887
SMARCD3	BANF1	O75531	875
SMARCD3	SMARCC1	Q92922	856
SMARCD3	SMARCA4	P51532	847
SMARCD3	GATA4	P43694	825
SMARCD3	SMARCA1	P28370	761
SMARCD3	MEGF8	Q7Z7M0	754
SMARCD3	NKX2-5	P52952	724
SMARCD3	SRCAP	Q6ZRS2	719
SMARCD3	CHD1	O14646	690
SMARCD3	SMARCE1	Q969G3	686
SMARCD3	ACTL6A	O96019	674
SMARCD3	SMARCB1	Q12824	663
SMARCD3	BRD2	P25440	655

IntAct

Human interaction partners of SMARCD3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
ARID1A	association	0.640	1
GRB2	physical association	0.400	1

BioGRID (190 interactions; top human partners by supporting records): SMARCA4 (Co-fractionation; 12 records), ARID1A (Co-fractionation; 9 records), SMARCE1 (Affinity Capture-MS; 8 records), SMARCC2 (Co-fractionation; 6 records), DPF2 (Affinity Capture-MS; 5 records), DPF3 (Affinity Capture-MS; 5 records), SMARCB1 (Co-fractionation; 5 records), SMARCD1 (Affinity Capture-MS; 5 records), BCL7A (Co-fractionation; 4 records), BCL7C (Co-fractionation; 4 records), MYOD1 (Proximity Label-MS; 4 records), SMARCA2 (Co-fractionation; 4 records), SS18 (Affinity Capture-MS; 4 records), ARID1B (Co-fractionation; 3 records), GNAQ (Proximity Label-MS; 3 records)

SIGNOR signaling

10 signaling 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

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ BRM-SIN3A complex	15	RBBP4, SMARCA2, SMARCB1, SMARCC2, SMARCD1, ACTL6A, HDAC1, HDAC2, PRMT5, SIN3A, SMARCD3, ARID1A, SMARCC1, SMARCD2, SMARCE1
★ BRG1-SIN3A complex	14	SMARCD1, SMARCD2, SMARCD3, ARID1A, RBBP4, SIN3A, SMARCA4, SMARCB1, SMARCE1, ACTL6A, HDAC2, PRMT5, SMARCC1, SMARCC2

Disease & clinical

Genetic variants

Variant evidence for SMARCD3: 52 ClinVar records (0 pathogenic / likely pathogenic); 13 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 21 predictions of 1,245):

Position(s)	Effect	Δscore	Sites
7:151239394–151239395	donor_loss	1.0000	4
7:151239498–151239499	acceptor_loss	1.0000	5
7:151239569	donor_gain	1.0000
7:151239573	donor_gain	1.0000
7:151239605	donor_gain	1.0000
7:151239748	acceptor_loss	1.0000	3
7:151242135–151242136	donor_loss	1.0000	3
7:151242245	acceptor_gain	1.0000
7:151242496	donor_gain	1.0000
7:151242605	acceptor_loss	1.0000

AlphaMissense

2,015 missense substitutions predicted likely pathogenic (of 3,185 scored), across 427 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M123	9	0.977	0.999
M372	9	0.922	0.994
D133	8	0.999	1.000
F238	8	0.999	1.000
D359	8	0.997	0.999
F201	8	0.996	1.000
F205	8	0.996	1.000
D236	8	0.996	1.000
H227	8	0.995	1.000
H222	8	0.994	1.000
D124	8	0.990	0.998
H343	8	0.990	1.000
F128	8	0.989	1.000
F375	8	0.989	0.999
D213	8	0.988	0.998
D220	8	0.987	0.999
F315	8	0.987	0.998
D430	8	0.984	0.993
F322	8	0.983	0.999
S207	8	0.978	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	favorable	5.62e-06
Pancreatic Adenocarcinoma (TCGA)	favorable	0.00087

Disease associations

OMIM: gene MIM:601737 | disease phenotypes:

GWAS associations

13 associations:

Study	Trait	p-value
GCST90002403_378	Red blood cell count	5e-16
GCST006979_171	Heel bone mineral density	6e-15
GCST90002383_67	Hematocrit	2e-14
GCST90002384_534	Hemoglobin	7e-13
GCST001848_186	IgG glycosylation	2e-10
GCST012396_9	Multiple myeloma	3e-10
GCST001848_628	IgG glycosylation	6e-10
GCST001848_607	IgG glycosylation	1e-9
GCST001848_494	IgG glycosylation	2e-9
GCST004483_3	Multiple myeloma	1e-8
GCST004028_4	Immunoglobulin light chain (AL) amyloidosis	5e-8
GCST001848_163	IgG glycosylation	7e-6
GCST003476_6	Eyebrow thickness	7e-6

EFO canonical traits (from GWAS)

5 canonical traits:

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 (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Cyclosporine	decreases expression, decreases methylation	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	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	affects cotreatment, increases oxidation, increases abundance	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Ozone	affects cotreatment, increases oxidation, increases abundance	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	decreases expression, increases abundance	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)

Via MONDO — disease-level, not drug-specific.