ACMSD

aminocarboxymuconate semialdehyde decarboxylase, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 2:134838616-134902034

Links

ENSG00000153086 ∙ NCBI:130013 ∙ OMIM:608889 ∙ HGNC:19288 ∙ Uniprot:Q8TDX5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epilepsy (Limited), mode of inheritance: AD

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACMSD 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	1	3
missense			23			23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1	1		2
splice region						0
non coding			3	1		4
Total	0	0	27	4	1

Variants in ACMSD

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

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

Position	Type	Phenotype	Significance	ClinVar
2-134838690-T-C		not specified	Uncertain significance (Dec 11, 2023)
2-134838696-T-C		not specified	Uncertain significance (Aug 02, 2021)
2-134838715-A-T		ACMSD-related disorder	Benign (May 03, 2018)
2-134845237-T-A		not specified	Uncertain significance (Dec 09, 2023)
2-134845251-T-C		not specified	Uncertain significance (Aug 10, 2021)
2-134859271-A-C		not specified	Uncertain significance (Jun 13, 2023)
2-134859275-G-T		not specified	Uncertain significance (Feb 05, 2024)
2-134863415-A-C		not specified	Uncertain significance (Jan 03, 2024)
2-134863427-G-C		not specified	Uncertain significance (Oct 14, 2021)
2-134863537-G-A		not specified	Uncertain significance (May 09, 2023)
2-134863563-G-A		not specified	Uncertain significance (Aug 08, 2023)
2-134863598-C-A		not specified	Uncertain significance (Dec 14, 2023)
2-134863599-C-G		not specified	Uncertain significance (Jan 23, 2024)
2-134863601-G-A			Likely benign (Aug 16, 2018)
2-134863606-C-T		not specified	Uncertain significance (Aug 14, 2023)
2-134863615-T-C		not specified	Uncertain significance (Jul 20, 2022)
2-134863630-C-T		not specified	Uncertain significance (Jul 20, 2021)
2-134863641-G-A		ACMSD-related disorder	Likely benign (Apr 09, 2019)
2-134867630-A-G		not specified	Uncertain significance (May 30, 2024)
2-134871006-A-G		not specified	Uncertain significance (Dec 22, 2023)
2-134871051-G-A		not specified	Uncertain significance (Oct 18, 2021)
2-134872455-G-T		See cases	Uncertain significance (Mar 12, 2019)
2-134872505-A-G		not specified	Uncertain significance (Dec 06, 2023)
2-134872507-G-A			Uncertain significance (Nov 01, 2022)
2-134872513-A-C		not specified	Uncertain significance (Jan 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACMSD	protein_coding	protein_coding	ENST00000356140	10	63488

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.39e-8	0.596	125694	0	53	125747	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0105	191	191	0.998	0.0000103	2225
Missense in Polyphen		77	74.137	1.0386		837
Synonymous	-0.618	79	72.3	1.09	0.00000464	618
Loss of Function	1.16	15	20.7	0.725	0.00000106	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000809	0.000802
Ashkenazi Jewish	0.00	0.00
East Asian	0.000601	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000116	0.000114
Middle Eastern	0.000601	0.000544
South Asian	0.000296	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts alpha-amino-beta-carboxymuconate-epsilon- semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can be converted non-enzymatically to quinolate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite. ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway. {ECO:0000269|PubMed:19843166}.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Tryptophan Metabolism;NAD+ biosynthetic pathways;Tryptophan metabolism;Tryptophan catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;2-amino-3-carboxymuconate semialdehyde degradation to glutaryl-CoA;Metabolism;L-kynurenine degradation;Tryptophan metabolism;Tryptophan degradation;superpathway of tryptophan utilization;tryptophan degradation (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.344
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.53

Haploinsufficiency Scores

• pHI: 0.162
• hipred: N
• hipred_score: 0.436
• ghis: 0.441

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acmsd

Gene ontology

• Biological process: tryptophan catabolic process;secondary metabolic process;protein complex oligomerization;negative regulation of quinolinate biosynthetic process;picolinic acid biosynthetic process;regulation of 'de novo' NAD biosynthetic process from tryptophan
• Cellular component: cytoplasm;cytosol
• Molecular function: aminocarboxymuconate-semialdehyde decarboxylase activity;protein binding;zinc ion binding;hydrolase activity