CYP2U1

cytochrome P450 family 2 subfamily U member 1, the group of Cytochrome P450 family 2

Basic information

Region (hg38): 4:107931548-107953461

Previous symbols: [ "SPG56" ]

Links

ENSG00000155016 ∙ NCBI:113612 ∙ OMIM:610670 ∙ HGNC:20582 ∙ Uniprot:Q7Z449 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 56 (Definitive), mode of inheritance: AR
• hereditary spastic paraplegia 56 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 56 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 56 (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 56, autosomal recessive with or without pseudoxanthoma elasticum	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	Dermatologic; Neurologic	23176821; 33107650

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP2U1 gene.

• Spastic paraplegia (197 variants)
• not provided (60 variants)
• Hereditary spastic paraplegia (29 variants)
• Hereditary spastic paraplegia 56 (26 variants)
• Inborn genetic diseases (19 variants)
• not specified (6 variants)
• CYP2U1-related condition (2 variants)
• See cases (2 variants)
• Abnormality of the nervous system (1 variants)
• Neurodegeneration;Global developmental delay (1 variants)
• Hereditary spastic paraplegia 5A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP2U1 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			2	49		51
missense	1	7	110	6	1	125
nonsense	4	4	1			9
start loss		1				1
frameshift	9	3	3			15
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1					1
splice region			1	2	2	5
non coding	1	1	9	20	14	45
Total	16	16	127	75	15

Highest pathogenic variant AF is 0.0000329

Variants in CYP2U1

This is a list of pathogenic ClinVar variants found in the CYP2U1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-107931574-C-T			Benign (Apr 08, 2019)
4-107931607-G-A		not specified	Benign (Aug 04, 2016)
4-107931619-ACCCGAGGCCGCCGGCGCCCGGACCATGTCGTC-A			Likely pathogenic (May 24, 2017)
4-107931622-C-A		not specified	Likely benign (Oct 06, 2016)
4-107931644-A-C		Hereditary spastic paraplegia 56	Pathogenic (-)
4-107931648-C-G		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
4-107931648-C-T		Spastic paraplegia • not specified • CYP2U1-related disorder	Conflicting classifications of pathogenicity (Nov 13, 2023)
4-107931653-C-T		Spastic paraplegia	Benign (Jan 29, 2024)
4-107931654-C-T		Spastic paraplegia	Uncertain significance (May 27, 2022)
4-107931670-G-GCCGGCCGAGGAC		Spastic paraplegia	Uncertain significance (Apr 10, 2021)
4-107931672-C-A		Spastic paraplegia	Uncertain significance (Feb 05, 2023)
4-107931673-G-A		Spastic paraplegia	Likely benign (Dec 06, 2021)
4-107931681-AC-A		Hereditary spastic paraplegia 56	Pathogenic (May 17, 2022)
4-107931686-C-T		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
4-107931696-CGCGCCTCCTGCGT-C		Hereditary spastic paraplegia 56	Pathogenic (Dec 07, 2012)
4-107931697-G-A		Spastic paraplegia	Likely benign (Jun 09, 2022)
4-107931700-C-G		Spastic paraplegia	Likely benign (Oct 18, 2022)
4-107931703-C-T		Spastic paraplegia • Hereditary spastic paraplegia	Conflicting classifications of pathogenicity (Jan 21, 2024)
4-107931707-C-T		Spastic paraplegia	Uncertain significance (Mar 12, 2022)
4-107931717-T-C		Spastic paraplegia	Uncertain significance (Jul 11, 2022)
4-107931731-C-T		Spastic paraplegia	Likely benign (Aug 22, 2023)
4-107931738-C-T		Spastic paraplegia	Uncertain significance (May 18, 2021)
4-107931741-G-T		Spastic paraplegia • Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
4-107931742-C-T		Spastic paraplegia	Likely benign (Dec 02, 2021)
4-107931750-C-A		Spastic paraplegia	Uncertain significance (Oct 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP2U1	protein_coding	protein_coding	ENST00000332884	5	22089

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00142	0.992	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.994	233	280	0.833	0.0000136	3536
Missense in Polyphen		87	108.44	0.80227		1333
Synonymous	0.644	103	112	0.922	0.00000567	1095
Loss of Function	2.39	8	19.3	0.414	0.00000107	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000333	0.000333
Ashkenazi Jewish	0.00	0.00
East Asian	0.000771	0.000707
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000185	0.000185
Middle Eastern	0.000771	0.000707
South Asian	0.0000661	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the hydroxylation of arachidonic acid, docosahexaenoic acid and other long chain fatty acids. May modulate the arachidonic acid signaling pathway and play a role in other fatty acid signaling processes. {ECO:0000269|PubMed:14660610}.
• Disease: DISEASE: Spastic paraplegia 56, autosomal recessive (SPG56) [MIM:615030]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. In SPG56, upper limbs are often also affected. Some SPG56 patients may have a subclinical axonal neuropathy. {ECO:0000269|PubMed:23176821}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: nicotine degradation III;Arachidonic acid metabolism - Homo sapiens (human);Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Leukotriene C4 Synthesis Deficiency;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Oxidation by Cytochrome P450;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE);Arachidonic acid metabolism;bupropion degradation;acetone degradation I (to methylglyoxal);Miscellaneous substrates;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Fatty acid metabolism;superpathway of tryptophan utilization;melatonin degradation I;superpathway of melatonin degradation;nicotine degradation IV (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.272
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.92

Haploinsufficiency Scores

• pHI: 0.200
• hipred: Y
• hipred_score: 0.557
• ghis: 0.554

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.177

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp2u1
• 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)

Gene ontology

• Biological process: organic acid metabolic process;xenobiotic metabolic process;exogenous drug catabolic process;oxidation-reduction process;omega-hydroxylase P450 pathway
• Cellular component: cytoplasm;endoplasmic reticulum membrane;integral component of membrane;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: monooxygenase activity;iron ion binding;steroid hydroxylase activity;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen;heme binding;aromatase activity