CYP7B1

cytochrome P450 family 7 subfamily B member 1, the group of Cytochrome P450 family 7

Basic information

Region (hg38): 8:64587763-64798737

Previous symbols: [ "SPG5A" ]

Links

ENSG00000172817 ∙ NCBI:9420 ∙ OMIM:603711 ∙ HGNC:2652 ∙ Uniprot:O75881 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 5A (Strong), mode of inheritance: AR
• congenital bile acid synthesis defect 3 (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia 5A (Supportive), mode of inheritance: AR
• congenital bile acid synthesis defect 3 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 5A (Strong), mode of inheritance: AR
• congenital bile acid synthesis defect 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bile acid synthesis defect, congenital, 3	AR	Gastrointestinal	Individuals may manifest with early-onset, progressive and severe cholestatic liver disease, and early recognition may allow treatment; Liver transplanation has been described	Gastrointestinal; Neurologic	7987300; 9802883; 18252231; 19187859; 19439420; 21567895; 21623769; 22384504

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP7B1 gene.

• Spastic paraplegia (43 variants)
• not provided (11 variants)
• Hereditary spastic paraplegia 5A (11 variants)
• Hereditary spastic paraplegia (2 variants)
• CYP7B1-related disorder (1 variants)
• Spastic ataxia (1 variants)
• Congenital bile acid synthesis defect 3 (1 variants)
• Hereditary spastic paraplegia 5A;Congenital bile acid synthesis defect 3 (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP7B1 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	117		120
missense	6	6	174	1	3	190
nonsense	19	2	1			22
start loss						0
frameshift	25	4	1			30
inframe indel	1		6			7
splice donor/acceptor (+/-2bp)	3	4	1			8
splice region			6	19	2	27
non coding			10	59	14	83
Total	54	16	196	177	17

Highest pathogenic variant AF is 0.0000329

Variants in CYP7B1

This is a list of pathogenic ClinVar variants found in the CYP7B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-64587798-C-T		CYP7B1-related disorder	Likely benign (Dec 19, 2023)
8-64589816-C-T		CYP7B1-related disorder	Likely benign (Oct 11, 2023)
8-64596067-A-C		Hereditary spastic paraplegia 5A	Uncertain significance (Apr 27, 2017)
8-64596113-T-C		Hereditary spastic paraplegia 5A	Benign (Jan 12, 2018)
8-64596240-T-A		Hereditary spastic paraplegia 5A	Uncertain significance (Jan 12, 2018)
8-64596305-A-C		Hereditary spastic paraplegia 5A • Hereditary spastic paraplegia	Conflicting classifications of pathogenicity (Jan 12, 2018)
8-64596531-C-T		Hereditary spastic paraplegia 5A	Uncertain significance (Jan 13, 2018)
8-64596593-G-A		Hereditary spastic paraplegia 5A	Benign/Likely benign (Feb 09, 2019)
8-64596631-T-C		Hereditary spastic paraplegia 5A	Uncertain significance (Apr 27, 2017)
8-64596656-T-C		Spastic paraplegia	Uncertain significance (Sep 09, 2022)
8-64596658-T-C			Uncertain significance (Jun 06, 2019)
8-64596666-T-C			Likely benign (Sep 25, 2018)
8-64596678-A-T		Spastic paraplegia	Uncertain significance (Jul 08, 2022)
8-64596682-G-A		Spastic paraplegia	Uncertain significance (Feb 07, 2021)
8-64596682-G-T		Spastic paraplegia	Uncertain significance (Feb 05, 2020)
8-64596687-C-T		Spastic paraplegia • CYP7B1-related disorder	Conflicting classifications of pathogenicity (Dec 11, 2023)
8-64596689-G-A		Spastic paraplegia	Uncertain significance (Apr 08, 2021)
8-64596695-C-A		Spastic paraplegia	Uncertain significance (Jun 10, 2022)
8-64596699-C-T		not specified • Spastic paraplegia	Conflicting classifications of pathogenicity (Jan 26, 2024)
8-64596702-C-A			Uncertain significance (May 11, 2018)
8-64596702-C-T		Spastic paraplegia	Likely benign (Sep 11, 2023)
8-64596702-C-CA		Spastic paraplegia	Conflicting classifications of pathogenicity (Dec 09, 2023)
8-64596706-C-T		Spastic paraplegia • Congenital bile acid synthesis defect 3 • Congenital bile acid synthesis defect 3;Hereditary spastic paraplegia 5A	Uncertain significance (Aug 09, 2022)
8-64596707-G-A		Hereditary spastic paraplegia 5A • Spastic paraplegia • Hereditary spastic paraplegia • Congenital bile acid synthesis defect 3;Hereditary spastic paraplegia 5A • CYP7B1-related disorder	Pathogenic/Likely pathogenic (Jan 29, 2024)
8-64596707-G-T		Spastic paraplegia	Uncertain significance (Aug 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP7B1	protein_coding	protein_coding	ENST00000310193	6	210999

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000330	0.942	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.395	272	254	1.07	0.0000126	3298
Missense in Polyphen		95	96.978	0.9796		1267
Synonymous	-1.66	114	93.5	1.22	0.00000468	963
Loss of Function	1.80	12	20.9	0.575	0.00000123	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.0000968	0.0000967
Middle Eastern	0.000326	0.000326
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Oxysterol 7alpha-hydroxylase that mediates formation of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) from 25- hydroxycholesterol (PubMed:10588945). Plays a key role in cell positioning and movement in lymphoid tissues: 7-alpha,25- dihydroxycholesterol (7-alpha,25-OHC) acts as a ligand for the G protein-coupled receptor GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells (By similarity). {ECO:0000250|UniProtKB:Q60991, ECO:0000269|PubMed:10588945}.
• Disease: DISEASE: Congenital bile acid synthesis defect 3 (CBAS3) [MIM:613812]: A disorder resulting in severe cholestasis, cirrhosis and liver synthetic failure. Hepatic microsomal oxysterol 7-alpha-hydroxylase activity is undetectable. {ECO:0000269|PubMed:9802883}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Primary bile acid biosynthesis - Homo sapiens (human);27-Hydroxylase Deficiency;Bile Acid Biosynthesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Oxidation by Cytochrome P450;Tryptophan metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Endogenous sterols;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Metabolism of steroids;Bile acid biosynthesis (Consensus)

Recessive Scores

• pRec: 0.245

Intolerance Scores

• loftool: 0.480
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.93

Haploinsufficiency Scores

• pHI: 0.321
• hipred: N
• hipred_score: 0.207
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.251

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp7b1
• Phenotype: reproductive system phenotype; hematopoietic system phenotype; immune system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: bile acid biosynthetic process;cholesterol metabolic process;sterol metabolic process;negative regulation of intracellular estrogen receptor signaling pathway;B cell chemotaxis;cholesterol homeostasis;positive regulation of epithelial cell proliferation;oxidation-reduction process;prostate gland epithelium morphogenesis
• Cellular component: endoplasmic reticulum membrane;organelle membrane
• Molecular function: iron ion binding;oxysterol 7-alpha-hydroxylase activity;heme binding