SPCS3

signal peptidase complex subunit 3

Basic information

Region (hg38): 4:176319966-176332245

Links

ENSG00000129128 ∙ NCBI:60559 ∙ OMIM:618854 ∙ HGNC:26212 ∙ Uniprot:P61009 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPCS3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPCS3 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						0
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	0	0

Variants in SPCS3

This is a list of pathogenic ClinVar variants found in the SPCS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-176322204-A-G		not specified	Uncertain significance (May 14, 2024)
4-176327163-C-T		not specified	Uncertain significance (Nov 25, 2024)
4-176327237-A-G		not specified	Uncertain significance (Oct 06, 2022)
4-176328206-G-A		not specified	Uncertain significance (Oct 04, 2022)
4-176328238-G-A		not specified	Uncertain significance (Mar 25, 2024)
4-176328282-C-A		not specified	Uncertain significance (Aug 14, 2024)
4-176328283-G-A		not specified	Uncertain significance (Mar 11, 2022)
4-176328317-C-T		not specified	Uncertain significance (May 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPCS3	protein_coding	protein_coding	ENST00000503362	5	12282

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.820	0.176	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.04	35	89.2	0.392	0.00000433	1153
Missense in Polyphen		4	24.742	0.16167		387
Synonymous	0.359	36	38.8	0.927	0.00000215	350
Loss of Function	2.20	0	5.66	0.00	2.36e-7	94

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the microsomal signal peptidase complex which removes signal peptides and other N-terminal peptides from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum. {ECO:0000269|PubMed:27499293}.
• Pathway: Protein export - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP);Incretin synthesis, secretion, and inactivation;Peptide hormone metabolism;SRP-dependent cotranslational protein targeting to membrane;Synthesis, secretion, and deacylation of Ghrelin;Translation;Metabolism of proteins;Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.0921
• hipred: Y
• hipred_score: 0.593
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.267

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spcs3

Gene ontology

• Biological process: signal peptide processing;proteolysis;protein targeting to ER
• Cellular component: endoplasmic reticulum;signal peptidase complex;endoplasmic reticulum membrane;integral component of membrane;organelle membrane
• Molecular function: peptidase activity