AHCY

adenosylhomocysteinase

Basic information

Region (hg38): 20:34280268-34311802

Links

ENSG00000101444 ∙ NCBI:191 ∙ OMIM:180960 ∙ HGNC:343 ∙ Uniprot:P23526 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase (Supportive), mode of inheritance: AR
• hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase (Strong), mode of inheritance: AR
• hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency	AR	Biochemical	Dietary restriction (eg, of methionine) and supplementation (eg, of phosphatidylcholine) may be beneficial in some individuals	Biochemical; Cardiovascular; Gastrointestinal; Neurologic	2380820; 15024124; 20852937; 21732553

ClinVar

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

• Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AHCY 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				64		64
missense		5	100	4		109
nonsense			2			2
start loss						0
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			3	8	1	12
non coding			12	29	13	54
Total	2	6	116	97	13

Highest pathogenic variant AF is 0.00000657

Variants in AHCY

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

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

Position	Type	Phenotype	Significance	ClinVar
20-34280355-T-A		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Benign (Jan 12, 2018)
20-34280356-G-A		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jan 13, 2018)
20-34280413-A-G		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jan 12, 2018)
20-34280451-C-G		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jan 13, 2018)
20-34280607-A-G		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jan 13, 2018)
20-34280617-T-A		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jan 13, 2018)
20-34280733-A-C		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Benign (Jan 12, 2018)
20-34280853-G-A		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jan 12, 2018)
20-34280922-C-T		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Apr 28, 2017)
20-34281037-G-C		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jul 15, 2022)
20-34281041-C-T		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (May 27, 2022)
20-34281051-C-T		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jul 18, 2022)
20-34281053-G-A		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
20-34281060-A-C			Uncertain significance (Oct 08, 2019)
20-34281072-A-G		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Likely benign (Dec 16, 2023)
20-34281097-C-T		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Likely benign (Aug 04, 2023)
20-34281105-T-A		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase • Inborn genetic diseases	Uncertain significance (Nov 02, 2023)
20-34281110-T-A		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Mar 10, 2022)
20-34281110-T-C		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Mar 14, 2022)
20-34281118-C-T		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Likely benign (Jul 18, 2022)
20-34281123-C-T		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Oct 30, 2023)
20-34281143-G-A		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase • Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
20-34281145-T-A		Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase	Uncertain significance (Jan 13, 2018)
20-34281163-C-T		Hypermethioninemia	Uncertain significance (Jun 14, 2016)
20-34281170-G-A		Inborn genetic diseases	Uncertain significance (May 24, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AHCY	protein_coding	protein_coding	ENST00000217426	10	31535

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0359	0.963	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.55	204	277	0.737	0.0000186	2837
Missense in Polyphen		37	82.573	0.44809		1051
Synonymous	-0.454	122	116	1.05	0.00000864	849
Loss of Function	2.79	6	19.2	0.312	9.25e-7	224

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000791	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.000294	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adenosylhomocysteine is a competitive inhibitor of S- adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine. {ECO:0000269|PubMed:12590576}.
• Disease: DISEASE: Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) [MIM:613752]: A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy. {ECO:0000269|PubMed:15024124, ECO:0000269|PubMed:16736098, ECO:0000269|PubMed:19177456, ECO:0000269|PubMed:20852937}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cysteine and methionine metabolism - Homo sapiens (human);Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics;S-Adenosylhomocysteine (SAH) Hydrolase Deficiency;Methionine Metabolism;Methionine Adenosyltransferase Deficiency;Glycine N-methyltransferase Deficiency;Hypermethioninemia;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Betaine Metabolism;Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type;Selenoamino Acid Metabolism;Cystathionine Beta-Synthase Deficiency;Folate Metabolism;Trans-sulfuration pathway;One Carbon Metabolism;Trans-sulfuration and one carbon metabolism;Methionine De Novo and Salvage Pathway;Ethanol effects on histone modifications;Methylation;Phase II - Conjugation of compounds;Metabolism of amino acids and derivatives;methionine degradation;TCR;Biological oxidations;Metabolism;Methionine Cysteine metabolism;Selenoamino acid metabolism;Metabolism of ingested SeMet, Sec, MeSec into H2Se;Methionine and cysteine metabolism;Sulfur amino acid metabolism;cysteine biosynthesis;superpathway of methionine degradation (Consensus)

Recessive Scores

• pRec: 0.559

Intolerance Scores

• loftool: 0.245
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.69

Haploinsufficiency Scores

• pHI: 0.815
• hipred: Y
• hipred_score: 0.513
• ghis: 0.543

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ahcy
• 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); skeleton phenotype

Zebrafish Information Network

• Gene name: ahcy
• Affected structure: hepatocyte
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: sulfur amino acid metabolic process;response to hypoxia;chronic inflammatory response to antigenic stimulus;one-carbon metabolic process;response to nutrient;S-adenosylhomocysteine catabolic process;methylation;S-adenosylmethionine cycle;circadian sleep/wake cycle
• Cellular component: nucleus;cytosol;melanosome;neuron projection;extracellular exosome
• Molecular function: adenosylhomocysteinase activity;protein binding;adenyl nucleotide binding;identical protein binding;NAD binding