CYP26B1

cytochrome P450 family 26 subfamily B member 1, the group of Cytochrome P450 family 26

Basic information

Region (hg38): 2:72129238-72147862

Links

ENSG00000003137 ∙ NCBI:56603 ∙ OMIM:605207 ∙ HGNC:20581 ∙ Uniprot:Q9NR63 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lethal occipital encephalocele-skeletal dysplasia syndrome (Strong), mode of inheritance: AR
• lethal occipital encephalocele-skeletal dysplasia syndrome (Moderate), mode of inheritance: AR
• lethal occipital encephalocele-skeletal dysplasia syndrome (Strong), mode of inheritance: AR
• lethal occipital encephalocele-skeletal dysplasia syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniosynostosis with radiohumeral fusions and other skeletal and craniofacial anomalies	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	22019272

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP26B1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP26B1 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				19	10	29
missense		2	47	9	3	61
nonsense		1				1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3		3
non coding			1	16	3	20
Total	0	3	49	44	16

Variants in CYP26B1

This is a list of pathogenic ClinVar variants found in the CYP26B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-72132183-A-G			Benign (Nov 08, 2018)
2-72132238-C-T		Inborn genetic diseases	Uncertain significance (May 08, 2023)
2-72132257-C-A		Inborn genetic diseases	Uncertain significance (Jul 22, 2022)
2-72132261-G-A		Inborn genetic diseases	Uncertain significance (Dec 15, 2022)
2-72132271-C-T		CYP26B1-related disorder • Inborn genetic diseases	Likely benign (Mar 19, 2024)
2-72132275-C-G		Inborn genetic diseases	Uncertain significance (Apr 08, 2024)
2-72132314-A-C		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
2-72132319-C-T			Likely benign (May 11, 2023)
2-72132323-G-T			Uncertain significance (Dec 13, 2022)
2-72132331-C-T			Uncertain significance (Mar 02, 2022)
2-72132348-C-A		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)
2-72132348-C-T		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
2-72132349-G-A			Benign/Likely benign (Jan 10, 2024)
2-72132349-G-T			Conflicting classifications of pathogenicity (Oct 24, 2023)
2-72132352-G-A			Conflicting classifications of pathogenicity (Nov 02, 2023)
2-72132353-G-C			Uncertain significance (Dec 07, 2023)
2-72132371-C-T			Likely benign (Aug 31, 2022)
2-72132389-A-G			Benign (Jan 31, 2024)
2-72132402-G-A		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
2-72132409-C-T		Inborn genetic diseases	Uncertain significance (Mar 07, 2023)
2-72132433-G-A		Lethal occipital encephalocele-skeletal dysplasia syndrome	Uncertain significance (Oct 11, 2019)
2-72132442-G-A		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
2-72132464-G-A			Likely benign (Apr 22, 2023)
2-72132476-A-G			Likely benign (Jun 08, 2018)
2-72132493-T-C		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP26B1	protein_coding	protein_coding	ENST00000001146	6	18801

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.980	0.0201	125667	0	78	125745	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	275	329	0.837	0.0000219	3299
Missense in Polyphen		79	136.7	0.57792		1322
Synonymous	-0.663	161	151	1.07	0.0000102	1070
Loss of Function	3.52	1	16.3	0.0612	7.11e-7	191

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000811	0.000793
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.000830	0.000816
Finnish	0.000190	0.000185
European (Non-Finnish)	0.000378	0.000360
Middle Eastern	0.000830	0.000816
South Asian	0.0000327	0.0000327
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the metabolism of retinoic acid (RA), rendering this classical morphogen inactive through oxidation. Involved in the specific inactivation of all-trans-retinoic acid (all-trans-RA), with a preference for the following substrates: all-trans-RA > 9-cis-RA > 13-cis-RA. Generates several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA, and 18-OH- RA. Essential for postnatal survival. Plays a central role in germ cell development: acts by degrading RA in the developing testis, preventing STRA8 expression, thereby leading to delay of meiosis. Required for the maintenance of the undifferentiated state of male germ cells during embryonic development in Sertoli cells, inducing arrest in G0 phase of the cell cycle and preventing meiotic entry. Plays a role in skeletal development, both at the level of patterning and in the ossification of bone and the establishment of some synovial joints. {ECO:0000269|PubMed:10823918, ECO:0000269|PubMed:22019272}.
• Disease: DISEASE: Radiohumeral fusions with other skeletal and craniofacial anomalies (RHFCA) [MIM:614416]: A disease characterized by craniofacial malformations, occipital encephalocele, radiohumeral fusions, oligodactyly, advanced osseous maturation, and calvarial mineralization defects. {ECO:0000269|PubMed:22019272}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Retinol metabolism - Homo sapiens (human);Adipogenesis;Oxidation by Cytochrome P450;Metapathway biotransformation Phase I and II;Vitamin A and Carotenoid Metabolism;Signaling by GPCR;Signal Transduction;Phase I - Functionalization of compounds;RA biosynthesis pathway;Vitamins;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Chemokine receptors bind chemokines;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Vitamin A (retinol) metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.151

Intolerance Scores

• loftool: 0.462
• rvis_EVS: 0
• rvis_percentile_EVS: 54.03

Haploinsufficiency Scores

• pHI: 0.320
• hipred: Y
• hipred_score: 0.707
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.363

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp26b1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; 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); endocrine/exocrine gland phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; vision/eye phenotype; 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; 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); embryo phenotype

Zebrafish Information Network

• Gene name: cyp26b1
• Affected structure: osteoblast
• Phenotype tag: abnormal
• Phenotype quality: star shaped

Gene ontology

• Biological process: cell fate determination;establishment of T cell polarity;kidney development;vitamin metabolic process;xenobiotic metabolic process;inflammatory response;male meiotic nuclear division;spermatogenesis;proximal/distal pattern formation;positive regulation of gene expression;sterol metabolic process;embryonic limb morphogenesis;response to vitamin A;retinoic acid catabolic process;tongue morphogenesis;regulation of T cell differentiation;retinoic acid receptor signaling pathway;negative regulation of retinoic acid receptor signaling pathway;oxidation-reduction process;bone morphogenesis;establishment of skin barrier;cornification;cellular response to retinoic acid;positive regulation of tongue muscle cell differentiation
• Cellular component: cytoplasm;endoplasmic reticulum membrane;organelle membrane
• Molecular function: retinoic acid binding;iron ion binding;retinoic acid 4-hydroxylase activity;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen;heme binding