SCAP

SREBF chaperone, the group of WD repeat domain containing

Basic information

Region (hg38): 3:47413680-47477126

Links

ENSG00000114650 ∙ NCBI:22937 ∙ OMIM:601510 ∙ HGNC:30634 ∙ Uniprot:Q12770 ∙ 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 SCAP gene.

• Inborn genetic diseases (52 variants)
• not provided (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCAP 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				3	6	9
missense			51	2		53
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	51	5	7

Variants in SCAP

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

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

Position	Type	Phenotype	Significance	ClinVar
3-47413883-C-T		not specified	Uncertain significance (Nov 15, 2023)
3-47413929-G-A			Benign (Dec 31, 2019)
3-47413944-G-C		not specified	Uncertain significance (Mar 11, 2022)
3-47414034-G-C			Benign (Dec 13, 2017)
3-47414059-T-C		not specified	Uncertain significance (Apr 08, 2022)
3-47414092-C-T		not specified	Uncertain significance (Feb 06, 2024)
3-47414198-C-T			Benign (Dec 07, 2017)
3-47414240-C-T			Benign (Aug 16, 2018)
3-47414265-G-T		not specified	Uncertain significance (Feb 16, 2023)
3-47414317-C-G		not specified	Uncertain significance (Jul 14, 2021)
3-47414320-G-A		not specified	Uncertain significance (Apr 18, 2023)
3-47414335-C-T		not specified	Uncertain significance (Mar 02, 2023)
3-47414582-T-C		not specified	Uncertain significance (Oct 25, 2022)
3-47414586-C-T		not specified	Uncertain significance (Oct 31, 2022)
3-47414591-G-A		not specified	Uncertain significance (Dec 08, 2023)
3-47414599-C-T			Benign (Jan 01, 2023)
3-47414632-C-A			Benign (Apr 24, 2018)
3-47414632-C-T			Likely benign (Dec 01, 2022)
3-47414637-C-T		not specified	Uncertain significance (Feb 08, 2023)
3-47414834-G-A		not specified	Uncertain significance (Apr 20, 2023)
3-47414885-G-A		not specified	Uncertain significance (Oct 03, 2022)
3-47414933-G-A		not specified	Uncertain significance (Aug 22, 2023)
3-47414934-C-T		not specified	Uncertain significance (Nov 17, 2023)
3-47414979-C-T		not specified	Uncertain significance (May 03, 2023)
3-47414981-C-T		not specified	Uncertain significance (May 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCAP	protein_coding	protein_coding	ENST00000265565	22	63414

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000291	1.00	125694	0	54	125748	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.57	590	794	0.743	0.0000506	8154
Missense in Polyphen		144	241.26	0.59687		2457
Synonymous	0.360	340	349	0.975	0.0000229	2797
Loss of Function	4.43	20	55.7	0.359	0.00000275	607

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000118	0.000118
Ashkenazi Jewish	0.000210	0.000198
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000315	0.000308
Middle Eastern	0.000163	0.000163
South Asian	0.000198	0.000196
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Escort protein required for cholesterol as well as lipid homeostasis. Regulates export of the SCAP/SREBF complex from the ER upon low cholesterol. Formation of a ternary complex with INSIG at high sterol concentrations leads to masking of an ER-export signal in SCAP and retention of the complex in the ER. Low sterol concentrations trigger release of INSIG, a conformational change in the SSC domain of SCAP, unmasking of the ER export signal, recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of SREBF in the Golgi, release of the transcription factor fragment of SREBF from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity). {ECO:0000250}.
• Pathway: Sterol Regulatory Element-Binding Proteins (SREBP) signalling;RAGE;Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);Metabolism;Metabolism of steroids;srebp control of lipid synthesis (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.285
• rvis_EVS: -2.19
• rvis_percentile_EVS: 1.39

Haploinsufficiency Scores

• pHI: 0.0528
• hipred: Y
• hipred_score: 0.595
• ghis: 0.574

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.941

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Scap
• Phenotype: liver/biliary system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: scap
• Affected structure: liver
• Phenotype tag: abnormal
• Phenotype quality: fatty

Gene ontology

• Biological process: response to hypoxia;immune response;aging;cholesterol metabolic process;response to insulin;SREBP signaling pathway;regulation of fatty acid biosynthetic process;cellular lipid metabolic process;negative regulation of cholesterol biosynthetic process;positive regulation of low-density lipoprotein particle receptor biosynthetic process
• Cellular component: Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;ER to Golgi transport vesicle membrane;integral component of membrane;protein-containing complex
• Molecular function: protein binding;sterol binding;protein-containing complex binding;unfolded protein binding