ALAS1

5'-aminolevulinate synthase 1

Basic information

Region (hg38): 3:52198085-52214327

Previous symbols: [ "ALAS3", "ALAS" ]

Links

ENSG00000023330 ∙ NCBI:211 ∙ OMIM:125290 ∙ HGNC:396 ∙ Uniprot:P13196 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALAS1 gene.

• Inborn genetic diseases (24 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALAS1 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						0
missense			24		1	25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	24	0	1

Variants in ALAS1

This is a list of pathogenic ClinVar variants found in the ALAS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-52199254-G-A		not specified	Uncertain significance (Jul 26, 2022)
3-52199279-G-A			Benign (Jan 05, 2018)
3-52199374-C-A		not specified	Uncertain significance (Oct 03, 2022)
3-52202615-G-A		not specified	Uncertain significance (Jul 27, 2021)
3-52202617-A-C		not specified	Uncertain significance (Dec 14, 2023)
3-52202663-G-A		not specified	Uncertain significance (Aug 13, 2021)
3-52202687-G-T		not specified	Uncertain significance (Oct 25, 2022)
3-52204006-C-A		not specified	Uncertain significance (Nov 18, 2022)
3-52204735-T-C		not specified	Uncertain significance (Dec 06, 2023)
3-52204752-G-A		not specified	Uncertain significance (Jan 10, 2023)
3-52204803-C-T		not specified	Uncertain significance (Jun 16, 2023)
3-52204806-A-G		not specified	Uncertain significance (Aug 22, 2023)
3-52204872-T-C		not specified	Uncertain significance (Dec 12, 2023)
3-52204896-C-T		not specified	Uncertain significance (Jan 04, 2022)
3-52204899-G-A		not specified	Uncertain significance (Aug 04, 2022)
3-52205873-G-A		not specified	Uncertain significance (May 30, 2023)
3-52206614-T-C		not specified	Uncertain significance (Jul 12, 2022)
3-52206626-G-T		not specified	Uncertain significance (Mar 04, 2024)
3-52206644-A-T		not specified	Uncertain significance (Nov 07, 2022)
3-52206676-C-T		not specified	Uncertain significance (Jan 30, 2024)
3-52206746-T-C		not specified	Uncertain significance (May 27, 2022)
3-52208182-G-A		not specified	Likely benign (Sep 29, 2023)
3-52211387-C-G		not specified	Uncertain significance (Apr 25, 2022)
3-52211444-C-T		not specified	Uncertain significance (Aug 11, 2022)
3-52211468-C-T		not specified	Uncertain significance (Aug 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALAS1	protein_coding	protein_coding	ENST00000394965	10	16242

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.110	0.890	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	310	375	0.828	0.0000213	4201
Missense in Polyphen		128	186.23	0.68732		2007
Synonymous	-0.889	151	138	1.10	0.00000728	1281
Loss of Function	3.55	7	26.8	0.261	0.00000150	302

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000500	0.000499
Ashkenazi Jewish	0.00	0.00
East Asian	0.000545	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000300	0.000290
Middle Eastern	0.000545	0.000544
South Asian	0.000131	0.000131
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Pathway: Glycine, serine and threonine metabolism - Homo sapiens (human);Porphyrin and chlorophyll metabolism - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Porphyrin Metabolism;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Constitutive Androstane Receptor Pathway;Nuclear Receptors Meta-Pathway;Mitochondrial biogenesis;Liver steatosis AOP;Heme Biosynthesis;hemoglobins chaperone;Heme biosynthesis;Metabolism of porphyrins;Glycine Serine metabolism;Metabolism;Porphyrin metabolism;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;Glycine, serine, alanine and threonine metabolism;FOXA2 and FOXA3 transcription factor networks;Organelle biogenesis and maintenance;tetrapyrrole biosynthesis;heme biosynthesis (Consensus)

Recessive Scores

• pRec: 0.449

Intolerance Scores

• loftool: 0.0429
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.49

Haploinsufficiency Scores

• pHI: 0.399
• hipred: Y
• hipred_score: 0.609
• ghis: 0.426

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.908

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alas1
• 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); embryo phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: protoporphyrinogen IX biosynthetic process;heme biosynthetic process;mitochondrion organization;regulation of lipid metabolic process
• Cellular component: nucleoplasm;mitochondrion;mitochondrial matrix;cytosol
• Molecular function: 5-aminolevulinate synthase activity;protein binding;pyridoxal phosphate binding;identical protein binding