ALDH1L1

Chr 3

aldehyde dehydrogenase 1 family member L1

Also known as: 10-FTHFDH, 10-fTHF, FDH, FTHFD

NCBI Gene: 10840 ENSG00000144908 UniProt: O75891 OMIM: 600249

This cytosolic enzyme catalyzes the NADP-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide, functioning in folate metabolism. Mutations cause autosomal recessive developmental delay, seizures, and brain malformations with onset in infancy or early childhood. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression. There is an antisense transcript that overlaps on the opposite strand with this gene locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.000

Z-score 2.76

OE 0.56 (0.40–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.60Z-score

OE missense 0.93 (0.86–1.00)

512 obs / 552.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.40–0.78)

0≤0.351.4

Missense OE?0.93 (0.86–1.00)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 25 / 45.0Missense obs/exp: 512 / 552.0Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in ALDH1L1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

1,172 rare PASS variants

Rare truncating (LoF)

1 in 300

160 rare PASS variants

Rare synonymous (reference)

1 in 78

512 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ALDH1L1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 51	1 in 730
South Asian	~43k	1 in 37	1 in 940
Remaining (unassigned)	~30k	1 in 37	1 in 670
European (Finnish)	~27k	1 in 130	1 in 1,500
Admixed American	~22k	1 in 46	1 in 880
African / African American	~21k	1 in 44	1 in 650
East Asian	~20k	1 in 37	1 in 430
Ashkenazi Jewish	~13k	1 in 300	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 40	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 22 coding exons well covered in gnomAD exomes; exon 15 marginal. Genomes: all 22.? see exons ↓