SPPL2C

signal peptide peptidase like 2C, the group of Peptidase family A22

Basic information

Region (hg38): 17:45844880-45847067

Links

ENSG00000185294 ∙ NCBI:162540 ∙ OMIM:608284 ∙ HGNC:28902 ∙ Uniprot:Q8IUH8 ∙ 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 SPPL2C gene.

• Inborn genetic diseases (47 variants)
• not provided (16 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPPL2C 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	3	5
missense			44	6	8	58
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	44	8	11

Variants in SPPL2C

This is a list of pathogenic ClinVar variants found in the SPPL2C region.

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

Position	Type	Phenotype	Significance	ClinVar
17-45844934-G-A		not specified	Uncertain significance (Jan 04, 2022)
17-45844934-G-T		not specified	Uncertain significance (Apr 22, 2022)
17-45844949-C-A		not specified	Likely benign (Jan 24, 2023)
17-45844952-A-C		not specified	Uncertain significance (Sep 22, 2023)
17-45844953-T-G		not specified	Uncertain significance (Jan 02, 2024)
17-45844967-G-A		not specified	Likely benign (Jun 09, 2022)
17-45844982-G-A		not specified	Uncertain significance (Jun 11, 2021)
17-45844991-G-A		not specified	Uncertain significance (Jul 09, 2021)
17-45845043-A-G			Likely benign (Jan 01, 2023)
17-45845062-C-A		not specified	Uncertain significance (Dec 12, 2023)
17-45845093-G-A		not specified	Uncertain significance (Feb 03, 2022)
17-45845108-C-T			Benign (Dec 31, 2019)
17-45845120-G-C		not specified	Uncertain significance (Jul 29, 2023)
17-45845123-G-A		not specified	Uncertain significance (Jan 23, 2024)
17-45845135-C-T			Benign (Apr 17, 2018)
17-45845151-G-A		not specified	Uncertain significance (Jul 12, 2022)
17-45845169-C-T			Benign (Jul 06, 2018)
17-45845208-G-A		not specified	Uncertain significance (Oct 25, 2023)
17-45845220-C-T		not specified	Uncertain significance (Jun 09, 2022)
17-45845265-T-C		not specified	Uncertain significance (Mar 01, 2024)
17-45845274-G-A			Benign (Jul 15, 2020)
17-45845282-G-A		not specified	Uncertain significance (Jan 09, 2024)
17-45845301-C-G		not specified	Uncertain significance (May 16, 2023)
17-45845306-C-A		not specified	Uncertain significance (Jul 26, 2021)
17-45845315-C-A		not specified	Uncertain significance (Jul 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPPL2C	protein_coding	protein_coding	ENST00000329196	1	2183

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000182	0.902	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.193	411	422	0.974	0.0000263	4368
Missense in Polyphen		125	134.61	0.92863		1560
Synonymous	0.415	180	187	0.961	0.0000123	1502
Loss of Function	1.50	8	14.1	0.568	7.79e-7	138

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: Intramembrane-cleaving aspartic protease (I-CLiP) that may be able to cleave type II membrane signal peptides in the hydrophobic plane of the membrane. {ECO:0000250}.

Intolerance Scores

• rvis_EVS: 2.19
• rvis_percentile_EVS: 98.1

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.146
• ghis: 0.417

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sppl2c

Gene ontology

• Biological process: membrane protein ectodomain proteolysis;membrane protein intracellular domain proteolysis;membrane protein proteolysis
• Cellular component: lysosomal membrane;endoplasmic reticulum membrane;Golgi-associated vesicle membrane;integral component of cytoplasmic side of endoplasmic reticulum membrane;integral component of lumenal side of endoplasmic reticulum membrane
• Molecular function: aspartic endopeptidase activity, intramembrane cleaving;protein homodimerization activity