ACER3

alkaline ceramidase 3, the group of Alkaline ceramidases

Basic information

Region (hg38): 11:76860859-77026797

Previous symbols: [ "PHCA" ]

Links

ENSG00000078124 ∙ NCBI:55331 ∙ OMIM:617036 ∙ HGNC:16066 ∙ Uniprot:Q9NUN7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• alkaline ceramidase 3 deficiency (Limited), mode of inheritance: AR
• alkaline ceramidase 3 deficiency (Strong), mode of inheritance: AR
• alkaline ceramidase 3 deficiency (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, progressive, early childhood-onset	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; Neurologic	26792856

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACER3 gene.

• Alkaline ceramidase 3 deficiency (2 variants)
• ACER3-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACER3 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	13	3	17
missense	1		32	1	1	35
nonsense	2	1				3
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	5	2	9
non coding				5	5	10
Total	3	1	34	19	9

Variants in ACER3

This is a list of pathogenic ClinVar variants found in the ACER3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-76860980-G-C		not specified	Uncertain significance (Sep 15, 2021)
11-76860986-G-A		not specified	Uncertain significance (Jul 17, 2023)
11-76860994-C-T			Likely benign (Jan 02, 2024)
11-76861021-C-G			Likely benign (Dec 02, 2021)
11-76861021-C-T		ACER3-related disorder	Benign (Jan 18, 2024)
11-76861027-G-A			Likely benign (Jan 12, 2023)
11-76861028-C-T			Likely benign (Dec 02, 2021)
11-76861029-T-C		Alkaline ceramidase 3 deficiency	Uncertain significance (-)
11-76861049-T-C			Uncertain significance (Sep 22, 2023)
11-76861050-A-G		not specified	Uncertain significance (Nov 07, 2022)
11-76861074-A-G		Alkaline ceramidase 3 deficiency	Uncertain significance (Dec 03, 2021)
11-76926575-T-G		not specified	Uncertain significance (Dec 09, 2023)
11-76926597-G-A			Uncertain significance (Jul 17, 2023)
11-76926600-C-T			Benign (Oct 13, 2023)
11-76926601-G-A			Uncertain significance (Dec 30, 2023)
11-76926607-G-A		ACER3-related disorder	Benign (Jan 31, 2024)
11-76926611-A-G			Uncertain significance (Dec 02, 2021)
11-76926631-G-C			Uncertain significance (Dec 18, 2023)
11-76926635-A-G			Uncertain significance (Jul 25, 2022)
11-76926636-G-A		ACER3-related disorder	Benign (Jan 31, 2024)
11-76926636-GC-AT			Uncertain significance (Oct 20, 2022)
11-76926638-G-A		not specified	Uncertain significance (Sep 27, 2022)
11-76926643-A-G			Uncertain significance (Apr 12, 2023)
11-76926686-C-G			Benign (Jan 31, 2024)
11-76958963-A-C			Likely benign (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACER3	protein_coding	protein_coding	ENST00000532485	11	165931

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.875	0.125	125735	0	10	125745	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.80	77	136	0.566	0.00000627	1728
Missense in Polyphen		24	50.508	0.47517		632
Synonymous	0.200	44	45.7	0.962	0.00000215	475
Loss of Function	3.52	3	20.0	0.150	9.72e-7	242

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000586	0.0000586
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000727	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes only phytoceramide into phytosphingosine and free fatty acid. Does not have reverse activity.
• Pathway: Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Krabbe disease;Metabolism of lipids;Metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.497
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.26

Haploinsufficiency Scores

• pHI: 0.287
• hipred: Y
• hipred_score: 0.768
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.824

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acer3
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: ceramide metabolic process;positive regulation of cell population proliferation;sphingolipid biosynthetic process;sphingosine biosynthetic process;phytosphingosine biosynthetic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of Golgi membrane;integral component of endoplasmic reticulum membrane
• Molecular function: phytoceramidase activity