SMARCD1
protein-codingSWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1, the group of BAF complex|GBAF complex|PBAF complex
Gene summary
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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0015452
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0032912
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0032912
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0032912
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SMARCD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003076.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 8 | 11 | |||
| missense | 4 | 3 | 91 | 4 | 1 | 103 |
| nonsense | 2 | 3 | 5 | |||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 4 | 5 | |||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 7 | 3 | 107 | 12 | 1 | 130 |
Highest pathogenic variant AF is 0.0000013682679
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003067.3 | 13 | MANE Select | |
| Ensembl | ENSP00000378414.4 | 13 | MANE Select | |
| RefSeq | NP_620710.2 | 12 | Standard | |
| Ensembl | ENSP00000370924.4 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| smarcd1 | Danio rerio | Structure: melanocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thermogenesis - Homo sapiens (human)
- Hepatocellular carcinoma - Homo sapiens (human)
- Androgen Receptor Network in Prostate Cancer
- Tumor suppressor activity of SMARCB1
- Gene expression (Transcription)
Biological Process
- nucleosome disassembly
- chromatin remodeling
- regulation of transcription by RNA polymerase II
- nervous system development
- chromatin-mediated maintenance of transcription
Molecular Function
- chromatin binding
- transcription coactivator activity
- signaling receptor binding
- protein binding
- protein-containing complex scaffold activity
Cellular Component
- nucleoplasm
- SWI/SNF complex
- intracellular membrane-bounded organelle
- npBAF complex
- nBAF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394963
- Coding exons
- 13
- Length
- 15741
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125742
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.44 | 117 | 279 | 0.420 | 0.0000163 | 3337 |
| Missense (PolyPhen) | 16 | 63.732 | 0.25105 | 762 | ||
| Synonymous | 0.903 | 88 | 99.5 | 0.885 | 0.00000512 | 1025 |
| Loss of Function | 4.78 | 2 | 30.5 | 0.0655 | 0.00000176 | 326 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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 (PubMed:8804307, PubMed:29374058). 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 (By similarity). Has a strong influence on vitamin D-mediated transcriptional activity from an enhancer vitamin D receptor element (VDRE). May be a link between mammalian SWI-SNF-like chromatin remodeling complexes and the vitamin D receptor (VDR) heterodimer (PubMed:14698202). Mediates critical interactions between nuclear receptors and the BRG1/SMARCA4 chromatin-remodeling complex for transactivation (PubMed:12917342). {ECO:0000250|UniProtKB:Q61466, ECO:0000269|PubMed:12917342, ECO:0000269|PubMed:14698202, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:8804307, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- LoFtool
- 0.0491
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.781
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |