CYP7B1

Summary

CYP7B1 (cytochrome P450 family 7 subfamily B member 1, HGNC:2652) is a protein-coding gene on chromosome 8q12.3, encoding Cytochrome P450 7B1 (O75881). A cytochrome P450 monooxygenase involved in the metabolism of endogenous oxysterols and steroid hormones, including neurosteroids.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway of extrahepatic tissues, which converts cholesterol to bile acids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be involved in the development of atherosclerosis, neurosteroid metabolism and sex hormone synthesis. Mutations in this gene have been associated with hereditary spastic paraplegia (SPG5 or HSP), an autosomal recessive disorder.

Source: NCBI Gene 9420 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CYP7B1-related disorder of oxysterol accumulation (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 614 total — 58 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes
• MANE Select transcript: NM_004820

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2652
Approved symbol	CYP7B1
Name	cytochrome P450 family 7 subfamily B member 1
Location	8q12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172817
Ensembl biotype	protein_coding
OMIM	603711
Entrez	9420

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000310193, ENST00000523954, ENST00000864435, ENST00000864436, ENST00000948771

RefSeq mRNA: 2 — MANE Select: NM_004820 NM_001324112, NM_004820

CCDS: CCDS6180

Canonical transcript exons

ENST00000310193 — 6 exons

Exon	Start	End
ENSE00001201335	64615691	64616281
ENSE00001201341	64624403	64624539
ENSE00001242909	64590851	64596929
ENSE00001242915	64798466	64798737
ENSE00003546021	64615026	64615232
ENSE00003570907	64604682	64604857

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 85.66.

FANTOM5 (CAGE): breadth broad, TPM avg 5.5392 / max 139.8339, expressed in 766 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93344	3.4985	635
93343	1.4405	434
93345	0.3031	189
93341	0.1082	60
93346	0.0951	49
93342	0.0939	52

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	85.66	gold quality
oral cavity	UBERON:0000167	84.96	gold quality
esophagus squamous epithelium	UBERON:0006920	81.99	gold quality
ventricular zone	UBERON:0003053	81.17	gold quality
skin of hip	UBERON:0001554	80.82	gold quality
corpus callosum	UBERON:0002336	80.55	gold quality
pigmented layer of retina	UBERON:0001782	79.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.87	gold quality
tibia	UBERON:0000979	79.72	gold quality
colonic epithelium	UBERON:0000397	79.29	gold quality
liver	UBERON:0002107	79.12	gold quality
oocyte	CL:0000023	79.10	gold quality
cartilage tissue	UBERON:0002418	78.29	silver quality
spinal cord	UBERON:0002240	78.27	gold quality
adipose tissue	UBERON:0001013	78.16	gold quality
right lung	UBERON:0002167	78.15	gold quality
right lobe of liver	UBERON:0001114	78.07	gold quality
gall bladder	UBERON:0002110	78.07	gold quality
parietal pleura	UBERON:0002400	77.91	gold quality
mammalian vulva	UBERON:0000997	77.89	gold quality
peripheral nervous system	UBERON:0000010	77.88	gold quality
tibial nerve	UBERON:0001323	77.88	gold quality
adrenal tissue	UBERON:0018303	77.79	gold quality
visceral pleura	UBERON:0002401	77.69	gold quality
pleura	UBERON:0000977	77.45	gold quality
connective tissue	UBERON:0002384	77.05	gold quality
epithelium of esophagus	UBERON:0001976	76.89	gold quality
ganglionic eminence	UBERON:0004023	76.83	gold quality
secondary oocyte	CL:0000655	76.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	76.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.83
E-ENAD-17	no	64.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ESR1, GABPA, NR1H2, NR1H3, PPARA, RORA, SP1, SP3, SREBF1

Literature-anchored findings (GeneRIF, showing 40)

• In Alzheimer’s disease (AD). CYP7B mRNA was significantly decreased (approximately 50% decline; P<0.05) in dentate neurons from AD subjects compared with controls. (PMID:14521990)
• Promotor activity of the human oxysterol 7alpha-hydroxylase gene is suppressed by sterol response element binding protein. (PMID:15003524)
• Single polymorphism in the CYP7B1 gene is associated with phenotypic differences in an expression system and a widely different allele frequency in two ethnic populations, with great differences in the incidence of prostate cancer. (PMID:15007371)
• CYP7B catalyzes oxysterol 7alpha-hydroxylation within the human prostate epithelium and an ERbeta-specific agonist, 7HD, is produced. (PMID:15181079)
• the 7-hydroxylation catalysed by P4507B1 preferentially takes place on DHEA, 5alpha-androstane-3beta,17beta-diol and epiandrosterone with major and minor formation of 7alpha- and 7beta-hydroxylated derivatives, respectively [cyp7b1] (PMID:15698543)
• Increased CYP7B activity leads to higher levels of 7alpha-OH-DHEA in synovial fluid which may contribute to the maintenance of chronic inflammation observed in rheumatoid arthritis patients. (PMID:15751070)
• In particular, the data suggest that androgens may control intraprostatic levels of estrogen via regulation of CYP7B1-mediated metabolism. (PMID:16630558)
• Presence of both CYP7B1 and 11beta-HSD1 in human skin. (PMID:17467270)
• Results suggest that -204A/C polymorphism in the CYP7A1 gene does not relate with hypertriglyceridemia but may has an effect on serum triglyceride and apoCIII levels in patients with endogenous HTG. (PMID:17680536)
• Identification of CYP7B1 as a novel ROTalpha (NR1F1) target gene and a functional cross-talk between RORalpha and liver X receptor (NR1H3). (PMID:18055760)
• Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. (PMID:18252231)
• tissue-specific steroid concentrations may have a strong impact on CYP7B1-dependent catalysis and thus on the levels of different CYP7B1-related steroids that can influence estrogen receptor beta signaling (PMID:18331353)
• regulation of CYP7B1 by ER can be mediated via the PI3K/Akt signal pathway, a regulatory pathway important for cellular survival and growth, suggest an important role for CYP7B1 in cellular growth, particularly in connection with estrogenic signalling. (PMID:18790053)
• Findings suggest CYP7B1 alterations to represent a rather frequent cause of hereditary spastic paraplegia that should be considered in patients with various clinical presentations. (PMID:18855023)
• screening of SPG5/CYP7B1 seems to have a low diagnostic yield in autosomal recessive and sporadic cases of spastic paraplegia, even in those with complicated clinical features. (PMID:19187859)
• we report the first Italian families with SPG5hereditary spastic paraplegia molecular characterization and describe two novel truncating mutations in CYP7B1. (PMID:19363635)
• Results confirm that CYP7B1 is the gene responsible for Spastic Paraplegia type 5. (PMID:19439420)
• CYP7B1 has multiple physiological functions and a role in liver failure in children and in neuropathy [review] (PMID:19687010)
• CYP7B1-mediated catalysis may play a role for control of the cellular levels of androgens, not only of estrogens. (PMID:19732851)
• Five CYP7B1 mutations, three of which are novel, were identified in four patients with hereditary spastic paraplegia type 5. (PMID:21214876)
• We identifies a Chinese family with hereditary spastic paraplegia due to compound heterozygous mutations in the CYP7B1 gene. (PMID:21452256)
• Description of a homology model for human CYP7B1 that provides valuable information on the active site architecture, along with docking studies that analyzed ligand-binding interactions. (PMID:21541746)
• analysis of the first Japanese patient with an oxysterol 7alpha-hydroxylase deficiency associated with compound heterozygous mutations of the CYP7B1 gene [case report] (PMID:21567895)
• investigation of CYP7B1-substrate binding modes (PMID:23180418)
• 4 novel mutations described in hereditary spastic paraplegia type 5A: 1 frameshift (c.509 delT p.L170fs), 1 premature stop codon (c.334 C>T p.R112X), 1 amino acid changing (c.440 G>A p.G147D) and 1 duplication (c.945_947 dupGGC p.A316AA) (PMID:24117163)
• 21-hydroxy-pregnenolone was identified as a new substrate, and overall low activity toward pregnanes could be related to the increased potency of 7-hydroxy derivatives produced by CYP7B1. (PMID:24491228)
• enduring sensory ataxia can be a pivotal sign in SPG5, and expands the phenotypic spectrum associated with mutations in CYP7B1 (PMID:24519355)
• Spastic paraplegia type 5 has a higher frequency in Taiwanese than in other ethnic groups, associated with a CYP7B1 founder mutation and its phenotype is characterized by pronounced dorsal column sensory loss, with cerebellar ataxia in some patients. (PMID:24641183)
• The patient was homozygous for a mutation (c.1249C>T) in CYP7B1 that alters a highly conserved residue in oxysterol 7 alpha-hydroxylase previously reported in a family with hereditary spastic paraplegia type 5 (PMID:24658845)
• Using an agnostic omics approach to focus on the association of CWP with body mass index, we have confirmed a steroid hormone association and identified a genetic variant upstream of the CYP genes, which likely controls this response. (PMID:25915148)
• The two novel variants cosegregated with pyramidal signs and autoimmune diseases suggesting that they might be susceptibility factors. (PMID:26370385)
• SPG11 and CYP7B1 were the most common cause of autosomal recessive hereditary spastic paraplegia in Greece. (PMID:26374131)
• Data indicated that the two GWAS-defined variants in the CYP7B1 region do not strongly influence HIV-1 infection susceptibility. (PMID:26399852)
• Data indicate two novel homozygous mutations (one frameshift and one missense mutation) detected in CYP7B1 (SPG5A), while no disease-causing mutation was identified for PNPLA6 (SPG39) and C19orf12 (SPG43). (PMID:26714052)
• miR17 induces epithelial-mesenchymal transition consistent with the cancer stem cell phenotype by regulating CYP7B1 expression in colon cancer. (PMID:27278684)
• This study provides evidence for CYP7B1 as a key regulator of three vital intracellular regulatory oxysterol levels. (PMID:30710743)
• AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases. (PMID:31337596)
• Clinical characteristics of Taiwanese patients with Hereditary spastic paraplegia type 5. (PMID:32202070)
• Description of clinical features and genetic analysis of one ultra-rare (SPG64) and two common forms (SPG5A and SPG15) of hereditary spastic paraplegia families. (PMID:33771085)
• The effect of CYP7B1 polymorphisms on the risk of coronary heart disease in Hainan Han population. (PMID:34493281)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp7b1	ENSDARG00000008858
mus_musculus	Cyp7b1	ENSMUSG00000039519
rattus_norvegicus	Cyp7b1	ENSRNOG00000009730

Paralogs (2): CYP39A1 (ENSG00000146233), CYP7A1 (ENSG00000167910)

Protein

Protein identifiers

Cytochrome P450 7B1 — O75881 (reviewed: O75881)

Alternative names: 24-hydroxycholesterol 7-alpha-hydroxylase, 25/26-hydroxycholesterol 7-alpha-hydroxylase, 3-hydroxysteroid 7-alpha hydroxylase, Oxysterol 7-alpha-hydroxylase

All UniProt accessions (1): O75881

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of endogenous oxysterols and steroid hormones, including neurosteroids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds of steroids with a preference for 7-alpha position. Usually metabolizes steroids carrying a hydroxy group at position 3, functioning as a 3-hydroxy steroid 7-alpha hydroxylase. Hydroxylates oxysterols, including 25-hydroxycholesterol and (25R)-cholest-5-ene-3beta,26-diol toward 7-alpha hydroxy derivatives, which may be transported to the liver and converted to bile acids. Via its product 7-alpha,25-dihydroxycholesterol, a ligand for the chemotactic G protein-coupled receptor GPR183/EBI2, regulates B cell migration in germinal centers of lymphoid organs, thus guiding efficient maturation of plasma B cells and overall antigen-specific humoral immune response. 7-alpha hydroxylates neurosteroids, including 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone) and pregnenolone, both involved in hippocampus-associated memory and learning. Metabolizes androstanoids toward 6- or 7-alpha hydroxy derivatives.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Widely expressed. Expressed in brain, testis, ovary, prostate, liver, colon, kidney, small intestine, thymus and spleen.

Disease relevance. Spastic paraplegia 5A, autosomal recessive (SPG5A) [MIM:270800] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by drugs voriconazole and metyrapone.

Pathway. Lipid metabolism; bile acid biosynthesis. Steroid hormone biosynthesis.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (2): NP_001311041, NP_004811* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002403	Cyt_P450_E_grp-IV	Family
IPR024204	Cyt_P450_CYP7A1-type	Family
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050529	CYP51A1-like	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.14.29 — 25/26-hydroxycholesterol 7alpha-hydroxylase (BRENDA: 5 organisms, 26 substrates, 13 inhibitors, 7 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5ALPHA-ANDROSTANE-3BETA,17BETA-DIOL	0.003–0.022	2
DEHYDROEPIANDROSTERONE	0.005–0.014	2
17BETA-ESTRADIOL	0.011	1
4-ANDROSTENE-3,17-DIONE	0.004	1
CHOLEST-5-ENE-3BETA,25-DIOL	0.001	1

Catalyzed reactions (Rhea), 10 shown:

• (25R)-cholest-5-ene-3beta,26-diol + reduced [NADPH–hemoprotein reductase] + O2 = (25R)-cholest-5-en-3beta,7alpha,26-triol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:19041)
• 25-hydroxycholesterol + reduced [NADPH–hemoprotein reductase] + O2 = 7alpha,25-dihydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:24308)
• 3beta-hydroxy-5alpha-androstan-17-one + reduced [NADPH–hemoprotein reductase] + O2 = 3beta,7alpha-dihydroxy-5alpha-androstan-17-one + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:43896)
• (24S)-hydroxycholesterol + reduced [NADPH–hemoprotein reductase] + O2 = (24S)-7alpha-dihydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46124)
• 3beta-hydroxyandrost-5-en-17-one + reduced [NADPH–hemoprotein reductase] + O2 = 3beta,7alpha-dihydroxyandrost-5-en-17-one + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46192)
• pregnenolone + reduced [NADPH–hemoprotein reductase] + O2 = 7alpha-hydroxypregnenolone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46196)
• 5alpha-androstane-3beta,17beta-diol + reduced [NADPH–hemoprotein reductase] + O2 = 5alpha-androstane-3beta,6alpha,17beta-triol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46200)
• androst-5-en-3beta,17beta-diol + reduced [NADPH–hemoprotein reductase] + O2 = androst-5-en-3beta,7alpha,17beta-triol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46204)
• (22R)-hydroxycholesterol + reduced [NADPH–hemoprotein reductase] + O2 = (22R,7alpha)-dihydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46460)
• (24S)-25-epoxycholesterol + reduced [NADPH–hemoprotein reductase] + O2 = (24S,25)-epoxy-7alpha-hydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46464)

UniProt features (22 total): sequence variant 18, transmembrane region 2, chain 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75881-F1	91.98	0.79

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 449 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-192105	Synthesis of bile acids and bile salts
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807	Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-211976	Endogenous sterols
R-HSA-5579013	Defective CYP7B1 causes SPG5A and CBAS3

MSigDB gene sets: 355 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_GLAND_MORPHOGENESIS, GOBP_CELL_CHEMOTAXIS, GOBP_PROSTATE_GLAND_MORPHOGENESIS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_ESTROGEN_RECEPTOR_SIGNALING_PATHWAY, REACTOME_ENDOGENOUS_STEROLS, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (13): steroid biosynthetic process (GO:0006694), bile acid biosynthetic process (GO:0006699), cholesterol metabolic process (GO:0008203), sterol metabolic process (GO:0016125), estrogen receptor signaling pathway (GO:0030520), negative regulation of intracellular estrogen receptor signaling pathway (GO:0033147), B cell chemotaxis (GO:0035754), cholesterol homeostasis (GO:0042632), epithelial cell proliferation (GO:0050673), positive regulation of epithelial cell proliferation (GO:0050679), prostate gland epithelium morphogenesis (GO:0060740), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202)

GO Molecular Function (11): iron ion binding (GO:0005506), steroid hydroxylase activity (GO:0008395), oxysterol 7-alpha-hydroxylase activity (GO:0008396), heme binding (GO:0020037), 24S-hydroxycholesterol 7-alpha-hydroxylase activity (GO:0033782), 25-hydroxycholesterol 7-alpha-hydroxylase activity (GO:0033783), monooxygenase activity (GO:0004497), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Synthesis of bile acids and bile salts	2
Bile acid and bile salt metabolism	1
Cytochrome P450 - arranged by substrate type	1
Metabolic disorders of biological oxidation enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid 7-alpha-hydroxylase activity	3
steroid metabolic process	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	2
oxidoreductase activity	2
lipid biosynthetic process	1
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
nuclear receptor-mediated steroid hormone signaling pathway	1
estrogen receptor signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of intracellular estrogen receptor signaling pathway	1
lymphocyte chemotaxis	1
sterol homeostasis	1
cell population proliferation	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
morphogenesis of an epithelium	1
developmental process involved in reproduction	1
prostate gland morphogenesis	1
primary metabolic process	1
lipid metabolic process	1
transition metal ion binding	1
monooxygenase activity	1
tetrapyrrole binding	1
binding	1
catalytic activity	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1879 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP7B1	NR1H4	Q96RI1	877
CYP7B1	HSD3B7	Q9H2F3	810
CYP7B1	ABCG5	Q9H222	810
CYP7B1	ABCG8	Q9H221	805
CYP7B1	NR0B2	Q15466	767
CYP7B1	CH25H	O95992	729
CYP7B1	CYP46A1	Q9Y6A2	682
CYP7B1	ABCB11	O95342	676
CYP7B1	PNPLA6	Q8IY17	676
CYP7B1	NR5A2	O00482	657
CYP7B1	AP5Z1	O43299	647
CYP7B1	SLC10A1	Q14973	627
CYP7B1	BAAT	Q14032	622
CYP7B1	SPG7	Q9UQ90	614
CYP7B1	GPR183	P32249	600

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CYP7B1	UBB	psi-mi:“MI:0914”(association)	0.560
CYP7B1	UBB	psi-mi:“MI:0915”(physical association)	0.560
DDR2	PLD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): UBB (Affinity Capture-MS), GHITM (Affinity Capture-MS), CYP7B1 (Proximity Label-MS), CYP7B1 (Proximity Label-MS), UBB (Affinity Capture-MS), CYP7B1 (Affinity Capture-MS), GSC2 (Cross-Linking-MS (XL-MS)), CYP7B1 (Proximity Label-MS)

ESM2 similar proteins: A0A067DE75, A0A067DT54, A0A067E1K2, A0A067ELB0, A0A1I9Q5Z0, A0A5B8ND22, A0A9Y1LLN2, A0AAW1JA93, A8WGA0, B2RXA7, B5BSX1, E1BHJ4, F1RE08, G3V7X8, H1A988, H2DH16, I1GQE7, O23051, O43174, O55127, O75881, O93323, P0DOX0, P0DXH4, P0DXH8, P79739, Q08D50, Q50EK0, Q50EK1, Q50EK5, Q50EK6, Q60991, Q63688, Q69F95, Q6EIG3, Q6JD68, Q6JTJ0, Q6V0L0, Q6WG30, Q811W2

Diamond homologs: A0A0L1JEW4, B8N2C8, B8NFL5, B8NUK6, E9QY26, I1RBR4, I1RJR2, I1S2M5, I3PFJ5, O14442, O18635, O46420, O75881, P0A513, P0DKI2, P0DXU9, P0DXV0, P10613, P10614, P14263, P49602, P50859, P9WPP8, P9WPP9, Q02315, Q09736, Q12664, Q16850, Q1JPY5, Q1ZXH9, Q4PJW3, Q4R8S6, Q4WNT5, Q5IZM4, Q5RE72, Q64654, Q759W0, Q7X7X4, Q8K0C4, Q9UVC3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AR	“down-regulates quantity by repression”	CYP7B1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

614 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	14
Uncertain significance	231
Likely benign	218
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027524	NM_004820.5(CYP7B1):c.806del (p.Asp269fs)	Pathogenic
120179	NM_004820.5(CYP7B1):c.889A>G (p.Thr297Ala)	Pathogenic
1322188	NM_004820.5(CYP7B1):c.1139C>G (p.Ser380Ter)	Pathogenic
1335945	NM_004820.5(CYP7B1):c.1081C>T (p.Arg361Ter)	Pathogenic
1372522	NM_004820.5(CYP7B1):c.421dup (p.Cys141fs)	Pathogenic
1390680	NM_004820.5(CYP7B1):c.1095T>G (p.Tyr365Ter)	Pathogenic
1948567	NM_004820.5(CYP7B1):c.173dup (p.Val59fs)	Pathogenic
2018998	NM_004820.5(CYP7B1):c.94dup (p.Ala32fs)	Pathogenic
2100941	NM_004820.5(CYP7B1):c.59dup (p.Leu22fs)	Pathogenic
219912	NM_004820.5(CYP7B1):c.334C>T (p.Arg112Ter)	Pathogenic
240072	NM_004820.5(CYP7B1):c.197C>G (p.Pro66Arg)	Pathogenic
240073	NM_004820.5(CYP7B1):c.321_324del (p.Lys107fs)	Pathogenic
240074	NM_004820.5(CYP7B1):c.525G>A (p.Trp175Ter)	Pathogenic
2735180	NM_004820.5(CYP7B1):c.250del (p.Leu84fs)	Pathogenic
2766272	NM_004820.5(CYP7B1):c.1006G>T (p.Gly336Ter)	Pathogenic
2780438	NM_004820.5(CYP7B1):c.1234-2A>G	Pathogenic
2789092	NM_004820.5(CYP7B1):c.792del (p.Gln265fs)	Pathogenic
2794110	NM_004820.5(CYP7B1):c.1074del (p.Ala359fs)	Pathogenic
2799932	NM_004820.5(CYP7B1):c.1079del (p.Leu360fs)	Pathogenic
280294	NM_004820.5(CYP7B1):c.793C>T (p.Gln265Ter)	Pathogenic
2805536	NM_004820.5(CYP7B1):c.1342_1353del (p.Lys448_Gly451del)	Pathogenic
2816771	NM_004820.5(CYP7B1):c.727_730del (p.Glu243fs)	Pathogenic
2842125	NM_004820.5(CYP7B1):c.1290_1291del (p.Gly432fs)	Pathogenic
2843995	NM_004820.5(CYP7B1):c.169G>T (p.Gly57Ter)	Pathogenic
2855000	NM_004820.5(CYP7B1):c.496_497delinsTG (p.Glu166Ter)	Pathogenic
2857111	NM_004820.5(CYP7B1):c.178del (p.Val59_Leu60insTer)	Pathogenic
2858223	NM_004820.5(CYP7B1):c.423_424delinsAC (p.Cys141_Tyr142delinsTer)	Pathogenic
2864838	NM_004820.5(CYP7B1):c.909G>A (p.Trp303Ter)	Pathogenic
2871585	NM_004820.5(CYP7B1):c.333_334del (p.Phe111fs)	Pathogenic
2875581	NM_004820.5(CYP7B1):c.1266dup (p.Lys423Ter)	Pathogenic

SpliceAI

2569 predictions. Top by Δscore:

Variant	Effect	Δscore
8:64603967:T:TA	donor_gain	1.0000
8:64604678:TTACC:T	donor_loss	1.0000
8:64604679:TA:T	donor_loss	1.0000
8:64604680:A:AC	donor_gain	1.0000
8:64604681:C:CC	donor_gain	1.0000
8:64604681:CCT:C	donor_gain	1.0000
8:64604854:CTTT:C	acceptor_gain	1.0000
8:64604855:TTT:T	acceptor_gain	1.0000
8:64604856:TT:T	acceptor_gain	1.0000
8:64604857:TC:T	acceptor_loss	1.0000
8:64604858:C:CC	acceptor_gain	1.0000
8:64604859:T:C	acceptor_loss	1.0000
8:64624397:TCTTA:T	donor_loss	1.0000
8:64624398:CTTAC:C	donor_loss	1.0000
8:64624400:T:TG	donor_loss	1.0000
8:64624402:C:CA	donor_loss	1.0000
8:64624402:CCA:C	donor_gain	1.0000
8:64797769:C:T	acceptor_gain	1.0000
8:64798460:GCTTA:G	donor_loss	1.0000
8:64798461:CTTA:C	donor_loss	1.0000
8:64798462:TTACC:T	donor_loss	1.0000
8:64798463:TA:T	donor_loss	1.0000
8:64596927:CTC:C	acceptor_gain	0.9900
8:64596928:TC:T	acceptor_gain	0.9900
8:64596929:CC:C	acceptor_gain	0.9900
8:64596929:CCTG:C	acceptor_loss	0.9900
8:64596930:CT:C	acceptor_loss	0.9900
8:64604680:AC:A	donor_gain	0.9900
8:64604681:CC:C	donor_gain	0.9900
8:64604855:TTTC:T	acceptor_gain	0.9900

AlphaMissense

3321 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:64596837:A:C	F442L	0.991
8:64596837:A:T	F442L	0.991
8:64596839:A:G	F442L	0.991
8:64596808:C:G	R452P	0.990
8:64596909:A:C	F418L	0.989
8:64596909:A:T	F418L	0.989
8:64596911:A:G	F418L	0.989
8:64604806:C:G	R370P	0.988
8:64604833:C:G	R361P	0.988
8:64624419:G:C	F81L	0.988
8:64624419:G:T	F81L	0.988
8:64624421:A:G	F81L	0.988
8:64596818:A:G	C449R	0.987
8:64604842:T:A	E358V	0.987
8:64596924:A:C	F413L	0.985
8:64596924:A:T	F413L	0.985
8:64596926:A:G	F413L	0.985
8:64615212:A:G	W291R	0.984
8:64615212:A:T	W291R	0.984
8:64596811:C:T	G451D	0.982
8:64596913:C:G	R417P	0.982
8:64596835:C:T	G443E	0.981
8:64604841:T:A	E358D	0.981
8:64604841:T:G	E358D	0.981
8:64604853:G:C	S354R	0.981
8:64604853:G:T	S354R	0.981
8:64604855:T:G	S354R	0.981
8:64596914:G:T	R417S	0.979
8:64604694:A:C	F407L	0.979
8:64604694:A:T	F407L	0.979

dbSNP variants (sampled 300 via entrez): RS1000006756 (8:64653214 G>T), RS1000010884 (8:64606261 T>C,G), RS1000017657 (8:64665858 G>T), RS1000021128 (8:64758513 T>G), RS1000023457 (8:64701927 C>G,T), RS1000029439 (8:64760897 C>T), RS1000048048 (8:64754146 G>A,C), RS1000064592 (8:64606135 T>C), RS1000080357 (8:64753729 A>G), RS1000087588 (8:64711203 G>A), RS1000129508 (8:64592507 A>G), RS1000138065 (8:64662599 A>G), RS1000163858 (8:64676976 G>T), RS1000171579 (8:64708096 G>A), RS1000183591 (8:64592794 G>A)

Disease associations

OMIM: gene MIM:603711 | disease phenotypes: MIM:108600, MIM:270800, MIM:303350, MIM:613812, MIM:214800

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital bile acid synthesis defect 3	Strong	Autosomal recessive
hereditary spastic paraplegia 5A	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
CYP7B1-related disorder of oxysterol accumulation	Definitive	AR

Mondo (5): spastic ataxia (MONDO:0017845), hereditary spastic paraplegia 5A (MONDO:0010047), hereditary spastic paraplegia (MONDO:0019064), congenital bile acid synthesis defect 3 (MONDO:0013439), CHD7-related CHARGE syndrome (MONDO:1010178)

Orphanet (4): Spastic ataxia (Orphanet:316226), Autosomal recessive spastic paraplegia type 5A (Orphanet:100986), Hereditary spastic paraplegia (Orphanet:685), Congenital bile acid synthesis defect type 3 (Orphanet:79302)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000079	Abnormality of the urinary system
HP:0000407	Sensorineural hearing impairment
HP:0000518	Cataract
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000952	Jaundice
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001271	Polyneuropathy
HP:0001317	Abnormal cerebellum morphology
HP:0001347	Hyperreflexia
HP:0001394	Cirrhosis
HP:0001396	Cholestasis
HP:0001399	Hepatic failure
HP:0001406	Intrahepatic cholestasis
HP:0001408	Bile duct proliferation
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001744	Splenomegaly
HP:0001761	Pes cavus
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002070	Limb ataxia
HP:0002078	Truncal ataxia
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002174	Postural tremor

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001353_6	HIV-1 susceptibility	1.000000e-06
GCST001854_5	Retinopathy in non-diabetics	4.000000e-06
GCST001859_31	Thiazide-induced adverse metabolic effects in hypertensive patients	5.000000e-06
GCST002701_27	Verbal declarative memory	3.000000e-06
GCST005724_4	Food allergy (maternal genetic effects)	9.000000e-06
GCST005951_62	Body mass index	2.000000e-11
GCST006461_9	Self-reported risk-taking behaviour	8.000000e-11
GCST006810_3	Self-reported risk-taking behaviour	6.000000e-11
GCST007326_113	Number of sexual partners	2.000000e-16
GCST009028_19	Adverse response to drug	3.000000e-07
GCST009391_910	Metabolite levels	4.000000e-06
GCST012037_3	Sleep start time	1.000000e-08
GCST012216_7	Vegetable consumption	2.000000e-08

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0004530	triglyceride measurement
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0005939	parental genotype effect measurement
EFO:0007016	food allergy measurement
EFO:0004340	body mass index
EFO:0008579	risk-taking behaviour
EFO:0009658	adverse effect
EFO:0010442	triacylglycerol 58:8 measurement
EFO:0008328	chronotype measurement
EFO:0008111	diet measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C566340	Bile Acid Synthesis Defect, Congenital, 3 (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067456 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP5, CYP7 and CYP8 families

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.77	Kd	1700	nM	CHEMBL5574621

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1S,2S,5S,6S,9S,10R)-16-bis(tert-butylamino)phosphoryl-1,5-dimethyl-17,18-diazapentacyclo[11.8.0.02,10.05,9.015,20]henicosa-15,17,19-trien-6-ol	2110322: Binding affinity to recombinant human CYP7B1 assessed as substrate-type binding by measuring dissociation constant by spectrophotometric titration method	kd	1.7000	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases expression, affects methylation	2
bisphenol S	decreases methylation, affects cotreatment, increases expression	2
Arsenic Trioxide	increases expression	2
Acetaminophen	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Lipopolysaccharides	affects cotreatment, affects expression, increases expression, affects reaction, affects response to substance	2
Nickel	increases expression	2
OTX015	increases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
mivebresib	increases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
chlortoluron	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
enilconazole	decreases expression	1
sodium arsenite	affects methylation	1
pregna-4,17-diene-3,16-dione	decreases reaction, increases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
nefazodone	affects cotreatment, decreases expression	1
27-hydroxycholesterol	increases hydroxylation	1
azoxystrobin	decreases expression	1
T0901317	decreases expression, increases activity	1
abrine	increases expression	1
alisol B 23-acetate	increases expression, decreases reaction	1
Atazanavir Sulfate	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5553658	ADMET	Binding affinity to recombinant human CYP7B1 assessed as substrate-type binding by measuring dissociation constant by spectrophotometric titration method	Design and synthesis of phosphoryl-substituted steroidal pyridazines (Pho-STPYRs) as potent estrogen receptor alpha inhibitors: targeted treatment of hormone-dependent breast cancer cells. — RSC Med Chem

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4MS	iPS-SPG5-Y275X	Induced pluripotent stem cell	Female
CVCL_A4NR	iPS-SPG5-R486C	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

53 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04297891	Not specified	UNKNOWN	Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06572046	Not specified	RECRUITING	STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies