SREBF2

sterol regulatory element binding transcription factor 2, the group of MicroRNA protein coding host genes|Basic helix-loop-helix proteins

Basic information

Region (hg38): 22:41833105-41907306

Links

ENSG00000198911

∙ NCBI:6721 ∙ OMIM:600481 ∙ HGNC:11290 ∙ Uniprot:Q12772 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hereditary spastic paraplegia (Limited), mode of inheritance: AR
multiple congenital anomalies/dysmorphic syndrome (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SREBF2 gene.

not_specified (149 variants)
not_provided (17 variants)
SREBF2-related_disorder (16 variants)
Hypercholesterolemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SREBF2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004599.4. 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				9 clinvar	5 clinvar	14
missense			147 clinvar	7 clinvar	2 clinvar	156
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	148	16	7

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SREBF2	protein_coding	protein_coding	ENST00000361204	19	74204

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.207	0.793	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.679	605	654	0.925	0.0000427	7310
Missense in Polyphen		180	225.29	0.79899		2486
Synonymous	-0.178	275	271	1.01	0.0000177	2405
Loss of Function	5.05	12	50.9	0.236	0.00000280	531

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000331	0.000329
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000357	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes. {ECO:0000250}.;
Pathway: Sterol Regulatory Element-Binding Proteins (SREBP) signalling;SREBF and miR33 in cholesterol and lipid homeostasis;Angiopoietin Like Protein 8 Regulatory Pathway;Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);Metabolism;Metabolism of steroids;srebp control of lipid synthesis;Activation of gene expression by SREBF (SREBP) (Consensus)

Recessive Scores

pRec: 0.474

Intolerance Scores

loftool: 0.357
rvis_EVS: -1.83
rvis_percentile_EVS: 2.09

Haploinsufficiency Scores

pHI: 0.660
hipred: Y
hipred_score: 0.800
ghis: 0.555

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Srebf2
Phenotype: liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name: srebf2
Affected structure: liver
Phenotype tag: abnormal
Phenotype quality: decreased size

Gene ontology

Biological process: negative regulation of transcription by RNA polymerase II;lipid metabolic process;cholesterol metabolic process;cellular response to starvation;positive regulation of cholesterol storage;cholesterol homeostasis;regulation of cholesterol biosynthetic process;positive regulation of transcription by RNA polymerase II;cellular response to low-density lipoprotein particle stimulus;cellular response to laminar fluid shear stress;regulation of lipid transport by negative regulation of transcription from RNA polymerase II promoter;negative regulation of cholesterol efflux;positive regulation of pri-miRNA transcription by RNA polymerase II;regulation of autophagy of mitochondrion;positive regulation of protein targeting to mitochondrion
Cellular component: Golgi membrane;nucleus;nucleoplasm;cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;ER to Golgi transport vesicle membrane;SREBP-SCAP-Insig complex;intracellular membrane-bounded organelle
Molecular function: C-8 sterol isomerase activity;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;protein binding;protein C-terminus binding;protein dimerization activity;E-box binding