CYP26A1

protein-coding

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

Gene summary

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 protein acts on retinoids, including all-trans-retinoic acid (RA), with both 4-hydroxylation and 18-hydroxylation activities. This enzyme regulates the cellular level of retinoic acid which is involved in regulation of gene expression in both embryonic and adult tissues. Two alternatively spliced transcript variants of this gene, which encode the distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000783.4

Inheritance

—

ClinVar variants

U:62B:5

Top phenotype

CYP26A1-related condition

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr10:93,073,475-93,077,885

External References & Databases

Ensembl (ENSG00000095596)

Transcript & Mutation Effects

hg38 • Region Span ~4.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP26A1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 5

CYP26A1-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000783.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	2 clinvar	3
missense			62 clinvar	2 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	62	3	2	67

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000783.4	RefSeq	NP_000774.2	7	MANE Select
ENST00000224356.5	Ensembl	ENSP00000224356.4	7	MANE Select
NM_057157.2	RefSeq	NP_476498.1	6	Standard
ENST00000371531.5	Ensembl	ENSP00000360586.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cyp26a1	Danio rerio	Structure: pectoral fin Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

cyp26a1

Danio rerio

Structure: pectoral fin

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinol metabolism - Homo sapiens (human)
Vitamin A Deficiency
Retinol Metabolism
Adipogenesis
Nuclear Receptors in Lipid Metabolism and Toxicity

Biological Process

kidney development
vitamin metabolic process
xenobiotic metabolic process
sterol metabolic process
response to retinoic acid

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
oxygen binding

Cellular Component

endoplasmic reticulum membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000224356
Coding exons: 7
Length: 4416
Individuals with no LoFs: 125697
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125748
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.435	261	282	0.927	0.0000133	3216
Missense (PolyPhen)		119	126.12	0.94352		1469
Synonymous	-1.36	138	119	1.16	0.00000580	1013
Loss of Function	0.863	18	22.4	0.803	0.00000116	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00047	0.00046	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00063	0.00060	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00026	0.00026	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a key role in retinoic acid metabolism. Acts on retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA. Capable of both 4-hydroxylation and 18- hydroxylation. Responsible for generation of several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA and 18-OH-RA. {ECO:0000269|PubMed:9228017, ECO:0000269|PubMed:9716180}.;

Intolerance Scores

LoFtool: 0.686
RVIS EVS: -0.18
RVIS percentile EVS: 40.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.528

Gene Damage Prediction

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