POR

Chr 7AR

cytochrome p450 oxidoreductase

Also known as: CPR, CYPOR, P450R

The protein functions as an endoplasmic reticulum oxidoreductase that transfers electrons from NADPH to cytochrome P450 enzymes, which are essential for steroid hormone metabolism, drug metabolism, and xenobiotic processing. Mutations cause autosomal recessive disorders including Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, as well as isolated disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency. These conditions primarily affect steroid hormone production and bone development, with genital anomalies and congenital adrenal hyperplasia being key clinical features.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismARLOEUF 0.842 OMIM phenotypes
Clinical SummaryPOR
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Gene-Disease Validity (ClinGen)
Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis · 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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ClinVar Variants
105 unique Pathogenic / Likely Pathogenic· 153 VUS of 700 total submissions
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Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.31
OE 0.58 (0.410.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.07Z-score
OE missense 1.01 (0.931.09)
448 obs / 443.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.410.84)
00.351.4
Missense OE1.01 (0.931.09)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 21 / 35.9Missense obs/exp: 448 / 443.7Syn Z: -0.67
DN
0.5674th %ile
GOF
0.7029th %ile
LOF
0.2970th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

700 submitted variants in ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic36
VUS153
Likely Benign375
Benign15
Conflicting29
69
Pathogenic
36
Likely Pathogenic
153
VUS
375
Likely Benign
15
Benign
29
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
41
3
25
0
69
Likely Pathogenic
27
4
5
0
36
VUS
3
120
30
0
153
Likely Benign
1
1
177
196
375
Benign
0
0
13
2
15
Conflicting
29
Total72128250198677

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

POR · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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