ASAH1

N-acylsphingosine amidohydrolase 1

Basic information

Region (hg38): 8:18055991-18084998

Previous symbols: [ "ASAH" ]

Links

ENSG00000104763 ∙ NCBI:427 ∙ OMIM:613468 ∙ HGNC:735 ∙ Uniprot:Q13510 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Farber lipogranulomatosis (Definitive), mode of inheritance: AR
• spinal muscular atrophy-progressive myoclonic epilepsy syndrome (Definitive), mode of inheritance: AR
• Farber lipogranulomatosis (Strong), mode of inheritance: AR
• spinal muscular atrophy-progressive myoclonic epilepsy syndrome (Strong), mode of inheritance: AR
• Farber lipogranulomatosis (Supportive), mode of inheritance: AR
• spinal muscular atrophy-progressive myoclonic epilepsy syndrome (Supportive), mode of inheritance: AR
• Farber lipogranulomatosis (Strong), mode of inheritance: AR
• spinal muscular atrophy-progressive myoclonic epilepsy syndrome (Strong), mode of inheritance: AR
• ASAH1-related sphingolipidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Farber lipogranulomatosis; Spinal muscular atrophy with progressive myoclonic epilepsy	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	Biochemical; Musculoskeletal; Neurologic; Pulmonary	13859108; 6423791; 2983648; 2854742; 3103372; 3130860; 8955159; 8892023; 11241842; 22703880; 24164096; 30029679
HSCT has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASAH1 gene.

• not provided (734 variants)
• Farber lipogranulomatosis (157 variants)
• Spinal muscular atrophy-progressive myoclonic epilepsy syndrome (35 variants)
• not specified (20 variants)
• Inborn genetic diseases (16 variants)
• Spinal muscular atrophy-progressive myoclonic epilepsy syndrome;Farber lipogranulomatosis (13 variants)
• Farber lipogranulomatosis;Spinal muscular atrophy-progressive myoclonic epilepsy syndrome (5 variants)
• ASAH1-related condition (3 variants)
• Childhood epilepsy with centrotemporal spikes (3 variants)
• Keloid formation (1 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita (1 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• See cases (1 variants)
• Variant of unknown significance (1 variants)
• Abnormality of the nervous system (1 variants)
• ASAH1-related disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASAH1 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			4	94		98
missense	6	24	245	6	8	289
nonsense	9	5	1			15
start loss		1				1
frameshift	15	1	2			18
inframe indel	2		4			6
splice donor/acceptor (+/-2bp)	3	14	1			18
splice region	1	3	23	31	4	62
non coding			38	156	97	291
Total	35	45	295	256	105

Highest pathogenic variant AF is 0.0000197

Variants in ASAH1

This is a list of pathogenic ClinVar variants found in the ASAH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-18056431-G-A		Farber lipogranulomatosis	Benign (Jan 13, 2018)
8-18056461-G-A		Farber lipogranulomatosis	Benign (Jan 13, 2018)
8-18056538-G-A		Farber lipogranulomatosis	Uncertain significance (Jan 13, 2018)
8-18056573-T-C		Farber lipogranulomatosis	Uncertain significance (Jan 12, 2018)
8-18056601-A-G		Farber lipogranulomatosis	Uncertain significance (Jan 13, 2018)
8-18056602-G-A		Farber lipogranulomatosis	Benign (Jan 13, 2018)
8-18056608-T-A		Farber lipogranulomatosis	Benign (Apr 27, 2017)
8-18056608-T-G		Farber lipogranulomatosis	Benign (Jan 12, 2018)
8-18056649-A-G		Farber lipogranulomatosis	Uncertain significance (Mar 16, 2018)
8-18056740-T-C		Farber lipogranulomatosis	Uncertain significance (Jan 12, 2018)
8-18056796-G-C		Farber lipogranulomatosis	Benign (Jan 13, 2018)
8-18056805-A-G		Farber lipogranulomatosis	Benign (Jan 13, 2018)
8-18056822-ACTTC-A		Farber lipogranulomatosis	Benign (Jun 14, 2016)
8-18056839-G-A		Farber lipogranulomatosis	Benign (Jan 13, 2018)
8-18056847-G-C		Farber lipogranulomatosis	Benign (Jan 13, 2018)
8-18056848-A-G		Farber lipogranulomatosis	Uncertain significance (Jan 13, 2018)
8-18056916-G-A			Likely benign (Jan 01, 2023)
8-18056917-A-T		Farber lipogranulomatosis	Uncertain significance (Jan 15, 2018)
8-18057033-A-G		Farber lipogranulomatosis	Uncertain significance (Jan 13, 2018)
8-18057075-A-G		Farber lipogranulomatosis	Uncertain significance (Jan 13, 2018)
8-18057161-G-A		Farber lipogranulomatosis	Uncertain significance (Jan 12, 2018)
8-18057166-G-A		Farber lipogranulomatosis	Likely benign (Jan 13, 2018)
8-18057178-G-C		Farber lipogranulomatosis	Likely benign (Jan 13, 2018)
8-18057181-G-A		Farber lipogranulomatosis	Uncertain significance (Jan 13, 2018)
8-18057200-C-T		Farber lipogranulomatosis	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASAH1	protein_coding	protein_coding	ENST00000381733	14	28561

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.26e-12	0.170	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.21	310	218	1.42	0.0000108	2669
Missense in Polyphen		83	69.879	1.1878		866
Synonymous	-0.0519	76	75.4	1.01	0.00000376	747
Loss of Function	0.846	21	25.6	0.820	0.00000129	314

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000443	0.000438
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000210	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid. {ECO:0000269|PubMed:7744740}.
• Disease: DISEASE: Spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME) [MIM:159950]: An autosomal recessive neuromuscular disorder characterized by childhood onset of motor deficits and progressive myoclonic seizures, after normal developmental milestones. Proximal muscle weakness and generalized muscular atrophy are due to degeneration of spinal motor neurons. Myoclonic epilepsy is generally resistant to conventional therapy. The disease course is progressive and leads to respiratory muscle involvement and severe handicap or early death from respiratory insufficiency. {ECO:0000269|PubMed:22703880, ECO:0000269|PubMed:24164096}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Signal Transduction of S1P Receptor;Neutrophil degranulation;phospholipids as signalling intermediaries;Metabolism of lipids;Innate Immune System;Immune System;Metabolism;Glycosphingolipid metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism;sphingosine and sphingosine-1-phosphate metabolism;Ceramide signaling pathway (Consensus)

Recessive Scores

• pRec: 0.289

Intolerance Scores

• loftool: 0.421
• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.31

Haploinsufficiency Scores

• pHI: 0.165
• hipred: N
• hipred_score: 0.170
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Asah1
• Phenotype: respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system 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); 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); renal/urinary system phenotype; skeleton phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: asah1b
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased branchiness

Gene ontology

• Biological process: ceramide metabolic process;glycosphingolipid metabolic process;neutrophil degranulation
• Cellular component: extracellular region;extracellular space;lysosomal lumen;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: catalytic activity;hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds;N-acylsphingosine amidohydrolase activity;ceramidase activity