SPG21

SPG21 abhydrolase domain containing, maspardin, the group of Abhydrolase domain containing

Basic information

Region (hg38): 15:64963022-64990310

Links

ENSG00000090487 ∙ NCBI:51324 ∙ OMIM:608181 ∙ HGNC:20373 ∙ Uniprot:Q9NZD8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mast syndrome (Strong), mode of inheritance: AR
• mast syndrome (Supportive), mode of inheritance: AR
• mast syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 21 (Mast syndrome)	AR	General	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	Neurologic	6024251; 14564668; 20301682; 24451228

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPG21 gene.

• Mast syndrome (5 variants)
• Hereditary spastic paraplegia (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPG21 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			5	20		25
missense			33			33
nonsense	1	2				3
start loss			1			1
frameshift	4	1				5
inframe indel						0
splice donor/acceptor (+/-2bp)		1	2			3
splice region			7	1		8
non coding			12	22	25	59
Total	5	4	53	42	25

Highest pathogenic variant AF is 0.0000131

Variants in SPG21

This is a list of pathogenic ClinVar variants found in the SPG21 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-64963027-T-T		Mast syndrome	Likely benign (Apr 27, 2017)
15-64963131-G-A		Mast syndrome	Likely benign (Apr 27, 2017)
15-64963363-T-T		Mast syndrome	Benign (Apr 27, 2017)
15-64963455-G-A		Mast syndrome	Uncertain significance (Jan 13, 2018)
15-64963545-T-T		Mast syndrome	Benign (Apr 27, 2017)
15-64963557-G-A		Mast syndrome	Uncertain significance (Jan 13, 2018)
15-64963573-A-G		Mast syndrome	Uncertain significance (Jan 12, 2018)
15-64963587-C-T		Mast syndrome	Uncertain significance (Mar 30, 2018)
15-64963601-A-T		Mast syndrome	Uncertain significance (Jan 13, 2018)
15-64963609-C-T		Mast syndrome	Uncertain significance (Jan 13, 2018)
15-64963638-G-A		SPG21-related disorder	Likely benign (Aug 09, 2022)
15-64963674-G-A			Likely benign (Aug 07, 2018)
15-64963676-C-T		not specified	Uncertain significance (Sep 28, 2022)
15-64963685-T-C		Mast syndrome • Hereditary spastic paraplegia • not specified	Uncertain significance (Aug 22, 2022)
15-64963701-C-T		Mast syndrome • not specified • Hereditary spastic paraplegia	Conflicting classifications of pathogenicity (Jan 29, 2024)
15-64963702-G-A		not specified	Uncertain significance (Jan 30, 2024)
15-64963703-C-T		Mast syndrome	Uncertain significance (Jun 08, 2022)
15-64963704-G-A		Mast syndrome • not specified • Hereditary spastic paraplegia	Benign/Likely benign (Jan 29, 2024)
15-64963727-G-T		Hereditary spastic paraplegia	Uncertain significance (Sep 01, 2018)
15-64963728-C-A		Hereditary spastic paraplegia	Uncertain significance (Sep 01, 2018)
15-64963733-G-T		Hereditary spastic paraplegia	Uncertain significance (Dec 12, 2016)
15-64963740-T-A		Mast syndrome	Uncertain significance (Nov 15, 2018)
15-64964055-C-T			Likely benign (Jun 06, 2019)
15-64965260-T-G			Likely benign (Jun 28, 2018)
15-64965308-G-A		Mast syndrome	Likely benign (Nov 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPG21	protein_coding	protein_coding	ENST00000204566	8	27287

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000661	0.981	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.16	127	169	0.749	0.00000883	2035
Missense in Polyphen		29	48.014	0.60399		624
Synonymous	-0.506	66	61.0	1.08	0.00000351	570
Loss of Function	2.07	8	17.3	0.462	9.05e-7	196

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000420	0.000297
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000273	0.000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role as a negative regulatory factor in CD4- dependent T-cell activation. {ECO:0000269|PubMed:11113139}.
• Pathway: Endocytosis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.237

Intolerance Scores

• loftool: 0.481
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.199
• hipred: Y
• hipred_score: 0.557
• ghis: 0.613

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.925

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spg21

Gene ontology

• Biological process: antigen receptor-mediated signaling pathway
• Cellular component: Golgi apparatus;cytosol;endosome membrane;trans-Golgi network transport vesicle;intracellular membrane-bounded organelle
• Molecular function: protein binding;CD4 receptor binding