ENOPH1

Chr 4

enolase-phosphatase 1

Also known as: E1, MASA, MST145, mtnC

NCBI Gene: 58478 ENSG00000145293 UniProt: Q9UHY7

ENOPH1 encodes a bifunctional enzyme that catalyzes key steps in the methionine salvage pathway, converting methylthioadenosine-derived intermediates to regenerate methionine. Biallelic mutations cause a rare autosomal recessive disorder characterized by intellectual disability, developmental delay, and seizures with onset in infancy or early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.82), suggesting some tolerance to haploinsufficiency while homozygous loss causes significant neurological impairment.

ResearchSummary from RefSeq, UniProt

Enables acireductone synthase activity. Involved in obsolete L-methionine salvage from methylthioadenosine. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.006

Z-score 2.06

OE 0.42 (0.23–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.83Z-score

OE missense 0.58 (0.48–0.69)

85 obs / 147.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.23–0.82)

0≤0.351.4

Missense OE?0.58 (0.48–0.69)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 6 / 14.4Missense obs/exp: 85 / 147.4Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in ENOPH1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

261 rare PASS variants

Rare truncating (LoF)

1 in 9,000

33 rare PASS variants

Rare synonymous (reference)

1 in 540

135 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ENOPH1. 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 330	1 in 13,000
South Asian	~43k	1 in 360	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 290	1 in 3,800
European (Finnish)	~27k	1 in 1,300	1 in 2,100
Admixed American	~22k	1 in 490	1 in 3,200
African / African American	~21k	1 in 450	≈ 1 in 17,000
East Asian	~20k	1 in 340	1 in 4,000
Ashkenazi Jewish	~13k	1 in 2,200	none seen
Middle Eastern	~2,884	1 in 240	none seen

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓