SMARCAL1

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1

Basic information

Region (hg38): 2:216412383-216483053

Links

ENSG00000138375

∙ NCBI:50485 ∙ OMIM:606622 ∙ HGNC:11102 ∙ Uniprot:Q9NZC9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Schimke immuno-osseous dysplasia (Definitive), mode of inheritance: AR
Schimke immuno-osseous dysplasia (Supportive), mode of inheritance: AR
Schimke immuno-osseous dysplasia (Strong), mode of inheritance: AR
Schimke immuno-osseous dysplasia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schimke immunoosseous dysplasia	AR	Allergy/Immunology/Infectious	Many individuals have an associated risk for opportunistic infection due to T-cell deficiency, and prophylaxis (eg, against P. carinii) and early and aggressive treatment of infections can be beneficial; BMT has been described	Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Renal	4282260; 2397176; 2066860; 8267014; 9674900; 9632175; 10528861; 10653321; 11113849; 0710226; 11799392; 12471207; 15523612; 16419127; 17089404; 17676601; 20301550

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCAL1 gene.

Schimke_immuno-osseous_dysplasia (1135 variants)
not_provided (107 variants)
Inborn_genetic_diseases (95 variants)
SMARCAL1-related_disorder (34 variants)
not_specified (16 variants)
Focal_segmental_glomerulosclerosis (10 variants)
Kidney_disorder (7 variants)
Nephrotic_syndrome (6 variants)
See_cases (4 variants)
Inherited_Immunodeficiency_Diseases (3 variants)
Familial_atrioventricular_septal_defect (2 variants)
Atypical_hemolytic-uremic_syndrome (2 variants)
Decreased_body_weight (2 variants)
Microcephaly (2 variants)
Steroid-resistant_nephrotic_syndrome (2 variants)
Small_for_gestational_age (2 variants)
Short_stature (2 variants)
Primary_microcephaly (2 variants)
Disproportionate_short-trunk_short_stature (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCAL1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014140.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			13 clinvar	430 clinvar	2 clinvar	445
missense	5 clinvar	19 clinvar	349 clinvar	35 clinvar	2 clinvar	410
nonsense	33 clinvar	6 clinvar	1 clinvar			40
start loss			1			1
frameshift	48 clinvar	18 clinvar	3 clinvar			69
splice donor/acceptor (+/-2bp)	2 clinvar	18 clinvar	4 clinvar			24
Total	88	61	371	465	4

Highest pathogenic variant AF is 0.000226964

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCAL1	protein_coding	protein_coding	ENST00000357276	16	70640

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000226	1.00	125655	0	93	125748	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.845	454	508	0.894	0.0000305	6228
Missense in Polyphen		165	197.89	0.83378		2307
Synonymous	-0.452	213	205	1.04	0.0000130	1915
Loss of Function	3.55	17	41.7	0.407	0.00000206	501

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000460	0.000460
Ashkenazi Jewish	0.00259	0.00258
East Asian	0.0000544	0.0000544
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000415	0.000413
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: ATP-dependent annealing helicase that binds selectively to fork DNA relative to ssDNA or dsDNA and catalyzes the rewinding of the stably unwound DNA. Rewinds single-stranded DNA bubbles that are stably bound by replication protein A (RPA). Acts throughout the genome to reanneal stably unwound DNA, performing the opposite reaction of many enzymes, such as helicases and polymerases, that unwind DNA. May play an important role in DNA damage response by acting at stalled replication forks. {ECO:0000269|PubMed:18974355, ECO:0000269|PubMed:19793861, ECO:0000269|PubMed:19793862}.;
Disease: DISEASE: Schimke immuno-osseous dysplasia (SIOD) [MIM:242900]: An autosomal recessive pleiotropic disorder characterized by spondyloepiphyseal dysplasia, renal dysfunction and immunodeficiency. Arteriosclerosis may also occur in some case. {ECO:0000269|PubMed:11799392, ECO:0000269|PubMed:18974355, ECO:0000269|PubMed:19793862}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Primary Focal Segmental Glomerulosclerosis FSGS;ATR signaling pathway (Consensus)

Recessive Scores

pRec: 0.121

Intolerance Scores

loftool: 0.0643
rvis_EVS: -0.13
rvis_percentile_EVS: 44.09

Haploinsufficiency Scores

pHI: 0.0676
hipred: N
hipred_score: 0.306
ghis: 0.548

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: N
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.908

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Smarcal1
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); hematopoietic system phenotype; skeleton phenotype; renal/urinary system phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name: smarcal1
Affected structure: nucleate erythrocyte
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: DNA strand renaturation;DNA metabolic process;DNA repair;regulation of transcription by RNA polymerase II;cellular response to DNA damage stimulus;replication fork processing;DNA rewinding;replication fork protection;t-circle formation
Cellular component: nucleus;nucleoplasm;DNA replication factor A complex;site of double-strand break;nuclear replication fork
Molecular function: helicase activity;protein binding;ATP binding;DNA-dependent ATPase activity;annealing helicase activity