SMARCE1

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1, the group of BAF complex|PBAF complex

Basic information

Region (hg38): 17:40624962-40648654

Links

ENSG00000073584 ∙ NCBI:6605 ∙ OMIM:603111 ∙ HGNC:11109 ∙ Uniprot:Q969G3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Coffin-Siris syndrome 1 (Strong), mode of inheritance: AD
• Coffin-Siris syndrome (Supportive), mode of inheritance: AD
• familial multiple meningioma (Supportive), mode of inheritance: AD
• familial meningioma (Definitive), mode of inheritance: AD
• Coffin-Siris syndrome 5 (Moderate), mode of inheritance: AD
• Coffin-Siris syndrome 5 (Strong), mode of inheritance: AD
• familial meningioma (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meningioma, familial, susceptibility to	AD	Oncologic	Awareness of the risk of neoplasms may allow early detection and treatment	Craniofacial; Musculoskeletal; Neurologic; Oncologic	23377182; 23906836; 25168959

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCE1 gene.

• Familial meningioma (22 variants)
• Hereditary cancer-predisposing syndrome (11 variants)
• not provided (3 variants)
• Coffin-Siris syndrome 5 (1 variants)
• Tessier cleft (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCE1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	231		237
missense	2	7	337	9	1	356
nonsense	13		5	1		19
start loss			1			1
frameshift	12	4	7			23
inframe indel			13			13
splice donor/acceptor (+/-2bp)	2	8	2			12
splice region		1	23	24	2	50
non coding			6	82	14	102
Total	29	19	377	323	15

Variants in SMARCE1

This is a list of pathogenic ClinVar variants found in the SMARCE1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-40628675-G-A			Benign (Nov 12, 2018)
17-40628785-T-C		Familial meningioma • Hereditary cancer-predisposing syndrome	Likely benign (Jan 19, 2024)
17-40628786-T-TAAA		Familial meningioma	Uncertain significance (Feb 24, 2021)
17-40628788-T-C		Familial meningioma • Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 06, 2024)
17-40628790-C-A		Familial meningioma • Hereditary cancer-predisposing syndrome • Rhabdoid tumor predisposition syndrome 1	Benign/Likely benign (Sep 01, 2024)
17-40628790-C-T		Familial meningioma • Coffin-Siris syndrome 5;Familial meningioma • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (May 10, 2024)
17-40628794-T-C		Hereditary cancer-predisposing syndrome • Familial meningioma	Likely benign (Jan 04, 2024)
17-40628795-T-A		Familial meningioma	Uncertain significance (May 18, 2022)
17-40628795-T-C		Hereditary cancer-predisposing syndrome • Familial meningioma	Conflicting classifications of pathogenicity (Mar 28, 2022)
17-40628799-C-T		Familial meningioma • Hereditary cancer-predisposing syndrome	Uncertain significance (Feb 19, 2022)
17-40628801-T-A		Familial meningioma	Uncertain significance (Jan 27, 2024)
17-40628801-T-C		Hereditary cancer-predisposing syndrome	Uncertain significance (Aug 29, 2023)
17-40628802-C-A		Familial meningioma	Uncertain significance (Oct 02, 2023)
17-40628802-C-T		Familial meningioma • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (Oct 17, 2024)
17-40628804-T-G		Familial meningioma • Hereditary cancer-predisposing syndrome	Uncertain significance (Nov 14, 2024)
17-40628806-T-C		Hereditary cancer-predisposing syndrome	Likely benign (Oct 03, 2022)
17-40628807-G-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 28, 2022)
17-40628808-G-A		Familial meningioma	Uncertain significance (Apr 19, 2023)
17-40628808-G-C		Familial meningioma • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (Nov 13, 2024)
17-40628808-G-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Aug 17, 2024)
17-40628809-T-C		Familial meningioma • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (Apr 22, 2024)
17-40628810-A-G		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 01, 2020)
17-40628810-A-T		Familial meningioma	Uncertain significance (Nov 04, 2023)
17-40628811-T-C		Familial meningioma • Hereditary cancer-predisposing syndrome • Coffin-Siris syndrome 5;Familial meningioma	Conflicting classifications of pathogenicity (Feb 28, 2024)
17-40628812-G-A		Familial meningioma • Hereditary cancer-predisposing syndrome	Likely benign (Dec 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCE1	protein_coding	protein_coding	ENST00000348513	10	23547

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000848	125665	0	1	125666	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.74	123	243	0.506	0.0000141	2736
Missense in Polyphen		5	14.884	0.33592		152
Synonymous	0.281	83	86.3	0.962	0.00000557	722
Loss of Function	4.44	1	24.9	0.0402	0.00000139	278

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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. 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). Required for the coactivation of estrogen responsive promoters by SWI/SNF complexes and the SRC/p160 family of histone acetyltransferases (HATs). Also specifically interacts with the CoREST corepressor resulting in repression of neuronal specific gene promoters in non-neuronal cells. {ECO:0000250|UniProtKB:O54941, ECO:0000303|PubMed:12672490, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
• Disease: DISEASE: Meningioma (MNGMA) [MIM:607174]: A common neoplasm of the central nervous system derived from arachnoidal cells. The majority of meningiomas are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Most cases are sporadic. Familial occurrence of meningioma is rare. {ECO:0000269|PubMed:23377182, ECO:0000269|PubMed:25249420}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Coffin-Siris syndrome 5 (CSS5) [MIM:616938]: A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. {ECO:0000269|PubMed:22426308, ECO:0000269|PubMed:23906836}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Androgen receptor signaling pathway;Pathways Affected in Adenoid Cystic Carcinoma;Tumor suppressor activity of SMARCB1;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;the information processing pathway at the ifn beta enhancer;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;AndrogenReceptor;Chromatin organization;chromatin remodeling by hswi/snf atp-dependent complexes;TNFalpha;Transcriptional regulation by RUNX1;Regulation of Androgen receptor activity;Validated nuclear estrogen receptor beta network (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.0639
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.997
• hipred: Y
• hipred_score: 0.794
• ghis: 0.612

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Smarce1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: nucleosome disassembly;chromatin remodeling;regulation of transcription by RNA polymerase II;neurogenesis;ATP-dependent chromatin remodeling;negative regulation of transcription, DNA-templated;positive regulation of nucleic acid-templated transcription
• Cellular component: nuclear chromosome;nuclear chromatin;nucleus;nucleoplasm;SWI/SNF complex;protein-containing complex;npBAF complex;nBAF complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;chromatin binding;transcription coactivator activity;RNA binding;protein binding;N-acetyltransferase activity;nuclear receptor binding;nucleosomal DNA binding;protein N-terminus binding