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 (Supportive), mode of inheritance: AR
mast syndrome (Limited), mode of inheritance: AR
mast syndrome (Strong), 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 (73 variants)
not_provided (35 variants)
not_specified (29 variants)
Hereditary_spastic_paraplegia (20 variants)
SPG21-related_disorder (3 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. These statistics are base on transcript: NM_000016630.7. 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			3 clinvar	28 clinvar		31
missense	1 clinvar		46 clinvar	1 clinvar		48
nonsense	1 clinvar	2 clinvar				3
start loss			1			1
frameshift	6 clinvar	1 clinvar				7
splice donor/acceptor (+/-2bp)		2 clinvar	1 clinvar			3
Total	8	5	51	29	0

Highest pathogenic variant AF is 0.00012391066

Loading clinvar variants...

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
Phenotype

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