POR

cytochrome p450 oxidoreductase, the group of Small nucleolar RNA protein coding host genes|MicroRNA protein coding host genes

Basic information

Region (hg38): 7:75899200-75986855

Links

ENSG00000127948 ∙ NCBI:5447 ∙ OMIM:124015 ∙ HGNC:9208 ∙ Uniprot:P16435 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (Strong), mode of inheritance: AR
• Antley-Bixler syndrome (Supportive), mode of inheritance: AD
• congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (Supportive), mode of inheritance: AR
• congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (Strong), mode of inheritance: AR
• Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis; Disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency	AR	Endocrine	Hydrocortisone replacement therapy can be effective for cortisol deficiency, including administation of stress-dose steroids; In males, testosterone therapy can help with undervirilization in puberty	Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	2932643; 0633130; 12116245; 11742006; 12917333; 15220035; 14758361; 14513299; 15793702; 16906539; 18559916; 19837910; 19884324; 20124576; 20410220; 20818252; 20844025; 21070833; 22162478

ClinVar

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

• Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (44 variants)
• Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (3 variants)
• Congenital adrenal hyperplasia (3 variants)
• not provided (2 variants)
• POR-related disorder (2 variants)
• Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency;Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis;Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POR 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			1	231	6	238
missense	2	6	155	3		166
nonsense	12	2				14
start loss						0
frameshift	29	2	1			32
inframe indel	1		3	1		5
splice donor/acceptor (+/-2bp)	2	15				17
splice region			11	38		49
non coding			18	159	29	206
Total	46	25	178	394	35

Highest pathogenic variant AF is 0.000210

Variants in POR

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

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

Position	Type	Phenotype	Significance	ClinVar
7-75915104-A-C		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Jan 12, 2018)
7-75915137-A-C		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Benign (Jan 12, 2018)
7-75915138-G-C		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Jan 15, 2018)
7-75915151-G-T		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Jan 13, 2018)
7-75915179-G-A		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency • POR-related disorder	Uncertain significance (Jan 12, 2018)
7-75915179-G-C		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Jan 13, 2018)
7-75915179-G-T		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Jan 13, 2018)
7-75915187-C-G		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Jan 13, 2018)
7-75915188-T-C		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Apr 27, 2017)
7-75915189-A-G		POR-related disorder	Likely benign (Feb 25, 2019)
7-75915190-T-C		POR-related disorder	Likely benign (Jan 05, 2021)
7-75954006-G-C		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Aug 30, 2023)
7-75954007-A-G		Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis • Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Benign (Feb 01, 2024)
7-75954016-C-T		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Likely benign (May 02, 2023)
7-75954034-C-T		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Likely benign (Jul 13, 2023)
7-75954035-G-A		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Mar 08, 2022)
7-75954037-G-A		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Likely benign (Aug 29, 2023)
7-75954040-C-T		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Likely benign (Nov 08, 2023)
7-75954041-G-T		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Pathogenic (Nov 30, 2023)
7-75954045-C-T		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Uncertain significance (Oct 04, 2022)
7-75954046-G-A		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Likely benign (Jan 29, 2024)
7-75954052-C-G		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Likely benign (May 22, 2023)
7-75954052-C-T		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Likely benign (Jul 19, 2022)
7-75954061-A-G		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Likely benign (Mar 19, 2023)
7-75954061-ATC-A		Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	Pathogenic (Mar 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POR	protein_coding	protein_coding	ENST00000461988	15	87656

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.42e-10	0.981	124568	0	92	124660	0.000369

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0717	448	444	1.01	0.0000306	4384
Missense in Polyphen		125	141.01	0.88647		1301
Synonymous	-0.668	214	202	1.06	0.0000162	1303
Loss of Function	2.31	21	35.9	0.585	0.00000187	381

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000736	0.000695
Ashkenazi Jewish	0.00	0.00
East Asian	0.000224	0.000223
Finnish	0.000125	0.0000928
European (Non-Finnish)	0.000499	0.000478
Middle Eastern	0.000224	0.000223
South Asian	0.000439	0.000425
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5. {ECO:0000255|HAMAP- Rule:MF_03212}.
• Disease: DISEASE: Antley-Bixler syndrome, with genital anomalies and disordered steroidogenesis (ABS1) [MIM:201750]: A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. {ECO:0000269|PubMed:14758361, ECO:0000269|PubMed:15264278, ECO:0000269|PubMed:15483095}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency (DISPORD) [MIM:613571]: A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome. {ECO:0000269|PubMed:14758361, ECO:0000269|PubMed:15220035}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Doxorubicin Pathway, Pharmacokinetics;Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics;Doxorubicin Metabolism Pathway;Integrated Lung Cancer Pathway;Oxidation by Cytochrome P450;Phase I - Functionalization of compounds;oxidative stress induced gene expression via nrf2;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;superpathway of tryptophan utilization;bile acid biosynthesis, neutral pathway;vitamin D₃ biosynthesis;melatonin degradation I;superpathway of melatonin degradation (Consensus)

Recessive Scores

• pRec: 0.542

Intolerance Scores

• loftool: 0.329
• rvis_EVS: -1.52
• rvis_percentile_EVS: 3.43

Haploinsufficiency Scores

• pHI: 0.165
• hipred: N
• hipred_score: 0.492
• ghis: 0.489

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Mouse Genome Informatics

• Gene name: Por
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); reproductive system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); craniofacial phenotype; vision/eye phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Gene ontology

• Biological process: regulation of growth plate cartilage chondrocyte proliferation;xenobiotic metabolic process;response to nutrient;carnitine metabolic process;response to hormone;flavonoid metabolic process;internal peptidyl-lysine acetylation;fatty acid oxidation;electron transport chain;positive regulation of chondrocyte differentiation;positive regulation of monooxygenase activity;response to drug;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;nitrate catabolic process;positive regulation of cholesterol biosynthetic process;positive regulation of smoothened signaling pathway;nitric oxide catabolic process;oxidation-reduction process;negative regulation of lipase activity;demethylation;cellular response to follicle-stimulating hormone stimulus;cellular response to peptide hormone stimulus;positive regulation of steroid hormone biosynthetic process;cellular organofluorine metabolic process
• Cellular component: mitochondrion;endoplasmic reticulum membrane;cytosol;membrane;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: NADPH-hemoprotein reductase activity;cytochrome-b5 reductase activity, acting on NAD(P)H;protein binding;nitric oxide dioxygenase activity;electron transfer activity;FMN binding;oxidoreductase activity;hydrolase activity;enzyme binding;iron-cytochrome-c reductase activity;flavin adenine dinucleotide binding;NADP binding