ALDH1L2

protein-coding

aldehyde dehydrogenase 1 family member L2, the group of Aldehyde dehydrogenases

Gene summary

This gene encodes a member of both the aldehyde dehydrogenase superfamily and the formyl transferase superfamily. This member is the mitochondrial form of 10-formyltetrahydrofolate dehydrogenase (FDH), which converts 10-formyltetrahydrofolate to tetrahydrofolate and CO2 in an NADP(+)-dependent reaction, and plays an essential role in the distribution of one-carbon groups between the cytosolic and mitochondrial compartments of the cell. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

MANE transcript

NM_001034173.4

Inheritance

ClinVar variants

P:1U:84B:4

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr12:105,019,784-105,107,643

External References & Databases

Ensembl (ENSG00000136010)

Transcript & Mutation Effects

hg38 • Region Span ~87.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

leukodystrophyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019046

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ALDH1L2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 3

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001034173.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			78 clinvar	4 clinvar		82
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	1	84	4	0	89

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001034173.4	RefSeq	NP_001029345.2	23	MANE Select
ENST00000258494.14	Ensembl	ENSP00000258494.9	23	MANE Select
ENST00000548418.1	Ensembl	ENSP00000447464.1	2	Standard
ENST00000552270.1	Ensembl	ENSP00000447538.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

One carbon pool by folate - Homo sapiens (human)
Metabolism
folate transformations I
Metabolism of folate and pterines
Metabolism of water-soluble vitamins and cofactors

Biological Process

one-carbon metabolic process
biosynthetic process
10-formyltetrahydrofolate catabolic process
folic acid metabolic process
oxidation-reduction process

Molecular Function

aldehyde dehydrogenase (NAD) activity
formyltetrahydrofolate dehydrogenase activity
hydroxymethyl-, formyl- and related transferase activity

Cellular Component

nucleus
mitochondrion
mitochondrial matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258494
Coding exons: 23
Length: 64788
Individuals with no LoFs: 125336
Homozygous LoFs: 2
Heterozygous LoFs: 410
Defined: 125748
p: 0.00164

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.37	414	500	0.828	0.0000254	6035
Missense (PolyPhen)		157	210.84	0.74464		2535
Synonymous	0.929	167	183	0.913	0.0000102	1776
Loss of Function	2.00	34	49.1	0.692	0.00000240	607

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0034	0.0034	notable
Latino/Admixed American	0.00081	0.00081	rare
Ashkenazi Jewish	0.0024	0.0024	notable
East Asian	0.0018	0.0018	notable
Finnish	0.00065	0.00065	rare
European (Non-Finnish)	0.0019	0.0018	notable
South Asian	0.0013	0.0013	notable
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.839
RVIS EVS: -1.08
RVIS percentile EVS: 7.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.742

Gene Damage Prediction

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