FTCDNL1

Chr 2

formiminotransferase cyclodeaminase N-terminal like

Also known as: FONG

NCBI Gene: 348751 ENSG00000226124 UniProt: E5RQL4 OMIM: 614308

The protein is predicted to bind folic acid and function as a transferase within membrane-bound cellular organelles. Mutations in this gene have been associated with neurodevelopmental disorders, though the clinical phenotype and inheritance patterns are not well-established based on current data. This gene shows moderate tolerance to loss-of-function variants (pLI 0.41, LOEUF 0.93), suggesting haploinsufficiency may not be the primary disease mechanism.

OMIM ResearchSummary from RefSeq

Predicted to enable folic acid binding activity and transferase activity. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.93

Clinical Summary— FTCDNL1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.

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ClinVar Variants

2 total variants — no pathogenic classifications of 2 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.405

Z-score 1.68

OE 0.20 (0.07–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.23Z-score

OE missense 0.58 (0.45–0.76)

40 obs / 68.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.07–0.93)

0≤0.351.4

Missense OE?0.58 (0.45–0.76)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 1 / 5.1Missense obs/exp: 40 / 68.8Syn Z: 0.62

This gene — mechanism propensity

0.6163th %ile

GOF

0.72top 25%

LOF

0.4628th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

2 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign1

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Synonymous	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	0	0
Likely Benign	1	1
Benign	0	0
Total	1	1

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

33 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap FTCDNL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →