GSAP

gamma-secretase activating protein

Basic information

Region (hg38): 7:77310750-77416349

Previous symbols: [ "PION" ]

Links

ENSG00000186088 ∙ NCBI:54103 ∙ OMIM:613552 ∙ HGNC:28042 ∙ Uniprot:A4D1B5 ∙ 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 GSAP gene.

• Inborn genetic diseases (38 variants)
• not specified (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 GSAP 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			32	6	1	39
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	32	6	2

Variants in GSAP

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

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

Position	Type	Phenotype	Significance	ClinVar
7-77311858-A-G		not specified	Uncertain significance (Jul 19, 2023)
7-77311861-T-C		not specified	Uncertain significance (May 08, 2023)
7-77311907-T-C		not specified	Uncertain significance (May 26, 2022)
7-77312117-T-C		not specified	Uncertain significance (Jun 17, 2022)
7-77312124-G-C		not specified	Uncertain significance (Mar 06, 2023)
7-77313493-G-T			Benign (Mar 29, 2018)
7-77314384-A-G		not specified	Likely benign (Apr 25, 2023)
7-77314387-A-G		not specified	Uncertain significance (Apr 14, 2022)
7-77314412-C-T		not specified	Uncertain significance (Feb 07, 2023)
7-77314426-C-T		not specified	Likely benign (Jul 15, 2021)
7-77314455-C-A		not specified	Likely benign (Nov 22, 2023)
7-77320767-T-C		not specified	Uncertain significance (Jan 07, 2022)
7-77321370-A-G		not specified	Uncertain significance (Aug 06, 2021)
7-77326259-G-A		not specified	Uncertain significance (Jun 06, 2023)
7-77329361-C-T		not specified	Uncertain significance (Aug 15, 2023)
7-77330281-G-C		not specified	Uncertain significance (Nov 20, 2023)
7-77330303-T-C		not specified	Uncertain significance (Aug 12, 2021)
7-77352966-G-A		not specified	Uncertain significance (Nov 08, 2022)
7-77355238-T-C		not specified	Likely benign (Feb 15, 2023)
7-77355242-C-G		not specified	Uncertain significance (Jan 24, 2024)
7-77355253-G-A		not specified	Likely benign (Jul 19, 2023)
7-77355254-C-T		not specified	Uncertain significance (May 16, 2022)
7-77355265-G-A		not specified	Likely benign (Aug 21, 2023)
7-77355319-G-A		not specified	Uncertain significance (Jun 29, 2023)
7-77355385-G-A		not specified	Uncertain significance (Jun 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GSAP	protein_coding	protein_coding	ENST00000257626	31	105650

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.55e-23	0.0844	125647	0	101	125748	0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.528	389	419	0.927	0.0000208	5601
Missense in Polyphen		72	92.056	0.78213		1344
Synonymous	0.957	142	157	0.903	0.00000842	1507
Loss of Function	1.54	42	54.3	0.774	0.00000247	713

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000500	0.000483
Ashkenazi Jewish	0.00	0.00
East Asian	0.000444	0.000435
Finnish	0.000195	0.000185
European (Non-Finnish)	0.000567	0.000554
Middle Eastern	0.000444	0.000435
South Asian	0.000343	0.000327
Other	0.000499	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of gamma-secretase activity, which specifically activates the production of amyloid-beta protein (amyloid-beta protein 40 and amyloid-beta protein 42), without affecting the cleavage of other gamma-secretase targets such has Notch. The gamma-secretase complex is an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate amyloid- beta, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD. {ECO:0000269|PubMed:20811458}.

Intolerance Scores

• rvis_EVS: 0.27
• rvis_percentile_EVS: 70.64

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.187
• ghis: 0.443

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gsap

Gene ontology

• Biological process: regulation of proteolysis;positive regulation of amyloid-beta formation
• Cellular component: trans-Golgi network
• Molecular function: amyloid-beta binding;protein binding