ASPH

aspartate beta-hydroxylase

Basic information

Region (hg38): 8:61500555-61714640

Links

ENSG00000198363 ∙ NCBI:444 ∙ OMIM:600582 ∙ HGNC:757 ∙ Uniprot:Q12797 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome (Strong), mode of inheritance: AR
• facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome (Supportive), mode of inheritance: AR
• facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs	AR	Ophthalmologic	Early surgical removal of the lens has been reported as necessary in order to preserve visual function by preventing irreversible corneal and trabecular meshwork damage	Craniofacial; Ophthalmologic	11241487; 23687502; 24768550

ClinVar

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

• not provided (103 variants)
• Inborn genetic diseases (27 variants)
• Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome (17 variants)
• not specified (4 variants)
• Malignant hyperthermia of anesthesia (1 variants)
• Exercise-induced malignant hyperthermia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASPH 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				10	6	16
missense			35	6	3	44
nonsense	4	2				6
start loss						0
frameshift	2					2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region		1	2	1	5	9
non coding				5	48	53
Total	6	2	37	21	57

Variants in ASPH

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

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

Position	Type	Phenotype	Significance	ClinVar
8-61503378-C-A		Inborn genetic diseases	Uncertain significance (May 30, 2023)
8-61503378-C-T		Inborn genetic diseases	Uncertain significance (Jan 28, 2023)
8-61503410-C-T			Likely benign (Jul 12, 2023)
8-61503433-G-A		Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome	Pathogenic (May 01, 2014)
8-61503452-C-CCAT		Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome	Pathogenic (Jun 17, 2021)
8-61503457-C-T			Uncertain significance (Aug 15, 2022)
8-61503461-G-A			Likely benign (Sep 20, 2023)
8-61503490-C-T		Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
8-61503506-G-C			Likely benign (Apr 15, 2023)
8-61503509-C-A			Uncertain significance (Jul 03, 2022)
8-61503510-CT-C		Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome	Pathogenic/Likely pathogenic (Jan 26, 2024)
8-61503515-G-A		Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome	Benign (Jan 31, 2024)
8-61503516-C-CAGAA			Likely benign (Aug 17, 2023)
8-61503614-G-A			Benign (Sep 04, 2018)
8-61517549-A-G		Inborn genetic diseases	Uncertain significance (Jun 29, 2022)
8-61517570-A-T		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
8-61517583-G-T		Inborn genetic diseases	Uncertain significance (Mar 08, 2024)
8-61517629-G-A			Benign (Mar 20, 2022)
8-61517649-T-C		Inborn genetic diseases	Likely benign (Jan 07, 2022)
8-61518052-T-C			Likely benign (Jul 17, 2023)
8-61518107-A-AT			Pathogenic (Jun 13, 2021)
8-61525971-A-G		Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome	Benign (Jan 31, 2024)
8-61525985-C-T			Pathogenic (Sep 21, 2022)
8-61525990-C-A			Likely benign (May 15, 2022)
8-61526021-AGGTT-CCC		Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome	Pathogenic (May 01, 2014)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASPH	protein_coding	protein_coding	ENST00000379454	25	214040

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.63e-15	0.987	125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.207	388	400	0.971	0.0000209	4988
Missense in Polyphen		114	144.19	0.79064		1694
Synonymous	-0.595	156	147	1.06	0.00000825	1338
Loss of Function	2.59	31	51.0	0.608	0.00000251	614

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000903	0.000895
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000587	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000365	0.000360
Middle Eastern	0.0000587	0.0000544
South Asian	0.000394	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins. {ECO:0000269|PubMed:11773073}.
• Pathway: hypoxia-inducible factor in the cardivascular system;Stimuli-sensing channels;Ion channel transport;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.181

Intolerance Scores

• loftool: 0.988
• rvis_EVS: -1.24
• rvis_percentile_EVS: 5.52

Haploinsufficiency Scores

• pHI: 0.0978
• hipred: Y
• hipred_score: 0.544
• ghis: 0.552

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.658

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Asph
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; limbs/digits/tail phenotype; muscle phenotype; digestive/alimentary phenotype; neoplasm; 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)

Gene ontology

• Biological process: muscle contraction;pattern specification process;negative regulation of cell population proliferation;electron transport chain;regulation of protein stability;ion transmembrane transport;limb morphogenesis;peptidyl-aspartic acid hydroxylation;positive regulation of proteolysis;roof of mouth development;face morphogenesis;activation of cysteine-type endopeptidase activity;regulation of protein depolymerization;regulation of cardiac conduction
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of membrane;cortical endoplasmic reticulum;sarcoplasmic reticulum membrane
• Molecular function: peptide-aspartate beta-dioxygenase activity;structural molecule activity;calcium ion binding;protein binding;structural constituent of muscle;electron transfer activity