NDOR1

Chr 9

NADPH dependent diflavin oxidoreductase 1

Also known as: CIAE1, NR1, bA350O14.9

NCBI Gene: 27158 ENSG00000188566 UniProt: Q9UHB4 OMIM: 606073

The protein is an NADPH-dependent diflavin reductase that serves as a central component of the cytosolic iron-sulfur protein assembly machinery, transferring electrons from NADPH to enable assembly of iron-sulfur cluster proteins. Mutations cause autosomal recessive developmental delay with variable intellectual disability and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an NADPH-dependent diflavin reductase that contains both flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) binding domains. The encoded protein catalyzes the transfer of electrons from NADPH through FAD and FMN cofactors to potential redox partners. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.08

Clinical Summary— NDOR1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

136 VUS of 157 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?

1.08LOEUF

pLI 0.000

Z-score 1.20

OE 0.76 (0.55–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.61Z-score

OE missense 1.09 (1.00–1.18)

422 obs / 388.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.76 (0.55–1.08)

0≤0.351.4

Missense OE?1.09 (1.00–1.18)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 23 / 30.1Missense obs/exp: 422 / 388.0Syn Z: -1.16

This gene — mechanism propensity

0.6163th %ile

GOF

0.77top 25%

LOF

0.2873th %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

157 submitted variants in ClinVar

ClinVar

Classification Summary

VUS136

Likely Benign7

136

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	136	0	136
Likely Benign	6	1	7
Benign	0	0	0
Total	142	1	143

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

View in ClinVar →

95 pathogenic / likely-pathogenic (of 108) ClinVar copy-number / structural variants overlap NDOR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →