SMARCA5

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5, the group of Chromatin accessibility complex|B-WICH chromatin-remodelling complex subunits|Myb/SANT domain containing

Basic information

Region (hg38): 4:143513701-143557486

Links

ENSG00000153147 ∙ NCBI:8467 ∙ OMIM:603375 ∙ HGNC:11101 ∙ Uniprot:O60264 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCA5 gene.

• Inborn genetic diseases (19 variants)
• not provided (15 variants)
• SMARCA5-related condition (1 variants)
• Intellectual disability (1 variants)
• Pes planus;Delayed CNS myelination;Global developmental delay;Hypotonia (1 variants)
• Pubertal developmental failure in females;Failure to thrive;Microcephaly;Short stature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCA5 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				1	2	3
missense	1	1	26	1		29
nonsense			1			1
start loss			1			1
frameshift						0
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding						0
Total	2	1	30	2	2

Variants in SMARCA5

This is a list of pathogenic ClinVar variants found in the SMARCA5 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-143513927-G-A			Uncertain significance (Aug 25, 2021)
4-143513947-C-A			Uncertain significance (Mar 24, 2022)
4-143513949-C-G		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
4-143513981-G-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
4-143514002-C-T			Benign (Dec 31, 2019)
4-143514043-T-G		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
4-143514055-C-T		Inborn genetic diseases	Uncertain significance (Mar 31, 2022)
4-143514064-C-G		Inborn genetic diseases	Uncertain significance (Oct 18, 2021)
4-143514067-C-G		Inborn genetic diseases	Uncertain significance (Nov 18, 2021)
4-143514070-C-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
4-143514072-A-C		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
4-143514077-T-G			Likely benign (Mar 13, 2018)
4-143514085-C-T		SMARCA5-related disorder	Likely benign (Apr 09, 2023)
4-143514087-G-A		Inborn genetic diseases	Uncertain significance (May 25, 2022)
4-143514090-G-T		Inborn genetic diseases	Likely benign (Jul 13, 2021)
4-143514091-C-A		Inborn genetic diseases	Uncertain significance (Mar 11, 2022)
4-143521452-C-T			Benign (Jun 13, 2018)
4-143521468-C-T			Uncertain significance (Jun 09, 2022)
4-143521502-C-T			Uncertain significance (Sep 29, 2022)
4-143521540-C-G		Inborn genetic diseases	Uncertain significance (Aug 28, 2023)
4-143524453-A-G			Uncertain significance (Jun 17, 2022)
4-143526281-G-A			Uncertain significance (Feb 07, 2022)
4-143528000-A-G		Intellectual disability	Likely pathogenic (Oct 04, 2022)
4-143528006-A-C		Short stature	Likely pathogenic (Nov 18, 2001)
4-143528648-GAAC-G		SMARCA5-related disorder	Uncertain significance (Mar 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCA5	protein_coding	protein_coding	ENST00000283131	24	44024

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.13e-10	125736	0	2	125738	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.42	198	558	0.355	0.0000288	6958
Missense in Polyphen		20	154.5	0.12945		1928
Synonymous	1.18	163	183	0.889	0.00000913	1868
Loss of Function	7.28	1	63.7	0.0157	0.00000368	760

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)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity. Complexes containing SMARCA5 are capable of forming ordered nucleosome arrays on chromatin; this may require intact histone H4 tails. Also required for replication of pericentric heterochromatin in S-phase specifically in conjunction with BAZ1A. Probably plays a role in repression of polI dependent transcription of the rDNA locus, through the recruitment of the SIN3/HDAC1 corepressor complex to the rDNA promoter. Essential component of the WICH complex, a chromatin remodeling complex that mobilizes nucleosomes and reconfigures irregular chromatin to a regular nucleosomal array structure. The WICH complex regulates the transcription of various genes, has a role in RNA polymerase I and RNA polymerase III transcription, mediates the histone H2AX phosphorylation at 'Tyr-142', and is involved in the maintenance of chromatin structures during DNA replication processes. Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. {ECO:0000269|PubMed:10880450, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:12198550, ECO:0000269|PubMed:12434153, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771}.
• Pathway: B-WICH complex positively regulates rRNA expression;Positive epigenetic regulation of rRNA expression;DNA Repair;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Epigenetic regulation of gene expression;Gene expression (Transcription);DNA Double-Strand Break Repair;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response (Consensus)

Recessive Scores

• pRec: 0.360

Intolerance Scores

• loftool: 0.0516
• rvis_EVS: -0.98
• rvis_percentile_EVS: 8.75

Haploinsufficiency Scores

• pHI: 0.979
• hipred: Y
• hipred_score: 0.825
• ghis: 0.726

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.952

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smarca5
• Phenotype: embryo phenotype; pigmentation phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); cellular phenotype

Zebrafish Information Network

• Gene name: smarca5
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: chromatin silencing at rDNA;nucleosome assembly;chromatin remodeling;DNA-templated transcription, initiation;regulation of transcription by RNA polymerase II;nucleosome positioning;CENP-A containing nucleosome assembly;ATP-dependent chromatin remodeling;positive regulation of gene expression, epigenetic;positive regulation of transcription, DNA-templated;cellular response to leukemia inhibitory factor
• Cellular component: condensed chromosome;fibrillar center;nucleus;nucleoplasm;chromatin silencing complex;NURF complex;RSF complex;nuclear replication fork
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;helicase activity;protein binding;ATP binding;ATPase activity;nucleosome binding;histone binding