CYP7B1

Chr 8AR

cytochrome P450 family 7 subfamily B member 1

Also known as: CBAS3, CP7B, SPG5A

This endoplasmic reticulum enzyme catalyzes the conversion of cholesterol to bile acids in extrahepatic tissues and is involved in neurosteroid metabolism. Mutations cause autosomal recessive spastic paraplegia 5A (SPG5) and congenital bile acid synthesis defect type 3. The pathogenic mechanism involves loss of normal enzyme function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 0.932 OMIM phenotypes
Clinical SummaryCYP7B1
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Gene-Disease Validity (ClinGen)
CYP7B1-related disorder of oxysterol accumulation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — CYP7B1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.000
Z-score 1.80
OE 0.57 (0.370.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.39Z-score
OE missense 1.07 (0.971.18)
272 obs / 254.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.370.93)
00.351.4
Missense OE1.07 (0.971.18)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 12 / 20.9Missense obs/exp: 272 / 254.3Syn Z: -1.66
DN
0.6938th %ile
GOF
0.6638th %ile
LOF
0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CYP7B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗