SREBF1

sterol regulatory element binding transcription factor 1, the group of Basic helix-loop-helix proteins|MicroRNA protein coding host genes

Basic information

Region (hg38): 17:17810399-17837002

Links

ENSG00000072310 ∙ NCBI:6720 ∙ OMIM:184756 ∙ HGNC:11289 ∙ Uniprot:P36956 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• IFAP syndrome 2 (Strong), mode of inheritance: AD
• hereditary mucoepithelial dysplasia (Strong), mode of inheritance: AD
• Hirschsprung disease (Supportive), mode of inheritance: AD
• IFAP syndrome 2 (Strong), mode of inheritance: AD
• IFAP syndrome 2 (Strong), mode of inheritance: AD
• hereditary mucoepithelial dysplasia (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis follicularis, atrichia, and photophobia syndrome 2; Mucoepithelial dysplasia, hereditary	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Ophthalmologic	31790666; 32497488; 32902915

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SREBF1 gene.

• IFAP syndrome 1, with or without BRESHECK syndrome (1 variants)
• IFAP syndrome 2 (1 variants)
• not provided (1 variants)
• Hereditary mucoepithelial dysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SREBF1 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				5	1	6
missense	1	1	95	6	4	107
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding					3	3
Total	1	2	96	11	8

Variants in SREBF1

This is a list of pathogenic ClinVar variants found in the SREBF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-17812659-A-C		Inborn genetic diseases	Uncertain significance (Dec 27, 2022)
17-17812813-C-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
17-17812839-T-C		Inborn genetic diseases	Uncertain significance (Apr 20, 2023)
17-17812861-C-T			Benign (Jul 13, 2018)
17-17813373-T-C		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
17-17813380-C-T		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
17-17813391-C-T		Inborn genetic diseases	Uncertain significance (Oct 04, 2023)
17-17813395-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
17-17813445-G-A		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
17-17813574-G-A		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
17-17813586-G-A		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
17-17813604-G-A		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
17-17813634-C-T			Uncertain significance (Jul 15, 2022)
17-17813636-C-T		Inborn genetic diseases	Uncertain significance (Apr 22, 2024)
17-17813637-G-T		Inborn genetic diseases	Uncertain significance (Dec 16, 2023)
17-17813643-C-G		Inborn genetic diseases	Uncertain significance (Aug 01, 2024)
17-17813675-C-T		Inborn genetic diseases	Uncertain significance (Jun 28, 2024)
17-17813687-G-A		Inborn genetic diseases	Uncertain significance (May 15, 2023)
17-17813693-G-A		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
17-17813711-T-C			Benign (Sep 01, 2022)
17-17814271-T-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
17-17814301-T-C		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
17-17814375-T-A		Inborn genetic diseases	Uncertain significance (Apr 01, 2024)
17-17814640-G-A			Likely benign (Aug 01, 2018)
17-17814664-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SREBF1	protein_coding	protein_coding	ENST00000355815	20	26613

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0147	0.985	125712	0	34	125746	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	548	695	0.789	0.0000454	7364
Missense in Polyphen		165	249.87	0.66034		2768
Synonymous	1.70	278	317	0.878	0.0000208	2620
Loss of Function	4.40	12	43.2	0.278	0.00000215	482

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000241
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000109
Finnish	0.000331	0.000323
European (Non-Finnish)	0.000134	0.000123
Middle Eastern	0.000111	0.000109
South Asian	0.000138	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3'). {ECO:0000250|UniProtKB:Q9WTN3}.
• Pathway: Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Metformin Pathway, Pharmacodynamic;AMP-activated Protein Kinase (AMPK) Signaling;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;SREBF and miR33 in cholesterol and lipid homeostasis;White fat cell differentiation;Adipogenesis;Liver X Receptor Pathway;Nuclear Receptors Meta-Pathway;RORA activates gene expression;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Liver steatosis AOP;Steatosis AOP;White fat cell differentiation;Transcriptional cascade regulating adipogenesis;ID signaling pathway;Circadian Clock;caspase cascade in apoptosis;Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);RORA activates gene expression;Metabolism;Metabolism of steroids;srebp control of lipid synthesis;RXR and RAR heterodimerization with other nuclear receptor;Activation of gene expression by SREBF (SREBP);Caspase Cascade in Apoptosis;mTOR signaling pathway (Consensus)

Recessive Scores

• pRec: 0.800

Intolerance Scores

• loftool: 0.388
• rvis_EVS: -0.79
• rvis_percentile_EVS: 12.6

Haploinsufficiency Scores

• pHI: 0.179
• hipred: Y
• hipred_score: 0.831
• ghis: 0.495

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• 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	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Srebf1
• 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); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: srebf1
• Affected structure: pancreatic B cell
• Phenotype tag: abnormal
• Phenotype quality: decreased area

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of heart rate by chemical signal;regulation of transcription by RNA polymerase II;lipid metabolic process;aging;circadian rhythm;cholesterol metabolic process;insulin receptor signaling pathway;lipid biosynthetic process;cellular response to starvation;response to glucose;positive regulation of triglyceride biosynthetic process;regulation of fatty acid metabolic process;lung development;intracellular receptor signaling pathway;positive regulation of histone deacetylation;regulation of protein stability;response to food;response to retinoic acid;response to progesterone;response to glucagon;mRNA transcription by RNA polymerase II;positive regulation of catalytic activity;fat cell differentiation;regulation of cholesterol biosynthetic process;positive regulation of cholesterol biosynthetic process;positive regulation of transcription by RNA polymerase II;negative regulation of insulin secretion;response to cAMP;cellular response to fatty acid;regulation of autophagy of mitochondrion;regulation of protein targeting to mitochondrion
• Cellular component: Golgi membrane;nucleus;nuclear envelope;nucleoplasm;cytoplasm;endoplasmic reticulum membrane;cytosol;ER to Golgi transport vesicle membrane;integral component of membrane;protein-containing complex
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;nuclear receptor activity;protein binding;enzyme activator activity;protein kinase binding;sterol response element binding;protein-containing complex binding;protein dimerization activity