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 (Strong), mode of inheritance: AR
• Schimke immuno-osseous dysplasia (Supportive), 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 (91 variants)
• not provided (5 variants)
• 9 conditions (2 variants)
• SMARCAL1-related disorder (1 variants)
• Nephrotic syndrome (1 variants)
• See cases (1 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.

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			2	394	2	398
missense	4	9	254	11	4	282
nonsense	33	2	2			37
start loss			1			1
frameshift	50	4	1			55
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	2	15	2			19
splice region	2		8	44	1	55
non coding			9	145	42	196
Total	89	31	274	550	48

Highest pathogenic variant AF is 0.000125

Variants in SMARCAL1

This is a list of pathogenic ClinVar variants found in the SMARCAL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-216412428-T-C		Schimke immuno-osseous dysplasia	Uncertain significance (Feb 16, 2018)
2-216412444-G-C		Schimke immuno-osseous dysplasia	Uncertain significance (Jan 12, 2018)
2-216412482-C-G		Schimke immuno-osseous dysplasia	Uncertain significance (Jan 12, 2018)
2-216412526-C-T		Schimke immuno-osseous dysplasia	Benign (Jan 12, 2018)
2-216412544-G-A		Schimke immuno-osseous dysplasia	Likely benign (Apr 27, 2017)
2-216412574-C-T		Schimke immuno-osseous dysplasia	Uncertain significance (Jan 12, 2018)
2-216412580-G-A		Schimke immuno-osseous dysplasia	Uncertain significance (Jan 13, 2018)
2-216412603-G-A		Schimke immuno-osseous dysplasia	Uncertain significance (Jan 13, 2018)
2-216412607-A-G		Schimke immuno-osseous dysplasia	Likely benign (Apr 27, 2017)
2-216412630-G-A		Schimke immuno-osseous dysplasia	Uncertain significance (Jan 12, 2018)
2-216412803-G-A			Uncertain significance (Jul 02, 2021)
2-216413869-T-C		Schimke immuno-osseous dysplasia	Uncertain significance (Jan 12, 2018)
2-216413893-G-T			Uncertain significance (Dec 24, 2023)
2-216414393-G-A			Benign (Nov 12, 2018)
2-216414437-G-A			Benign (May 04, 2020)
2-216414657-C-A		Schimke immuno-osseous dysplasia	Uncertain significance (Jan 13, 2018)
2-216414705-A-G		SMARCAL1-related disorder	Uncertain significance (Nov 04, 2023)
2-216414709-C-T		Schimke immuno-osseous dysplasia	Uncertain significance (Aug 28, 2021)
2-216414713-G-A		Schimke immuno-osseous dysplasia	Likely benign (Jul 31, 2023)
2-216414729-C-G		Schimke immuno-osseous dysplasia	Uncertain significance (Mar 04, 2022)
2-216414733-G-T		Schimke immuno-osseous dysplasia	Uncertain significance (Jun 23, 2022)
2-216414737-A-G		Schimke immuno-osseous dysplasia	Likely benign (Jan 05, 2022)
2-216414745-A-T		Schimke immuno-osseous dysplasia • Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
2-216414753-C-T		Schimke immuno-osseous dysplasia	Pathogenic (Sep 08, 2023)
2-216414754-G-A		Schimke immuno-osseous dysplasia	Uncertain significance (Jul 12, 2022)

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