NDRG4

Chr 16

NDRG family member 4

Also known as: BDM1, SMAP-8, SMAP8

The protein maintains intracerebral BDNF levels necessary for spatial learning and neuronal survival during ischemic stress, and modulates growth factor signaling pathways including ERK1/2 phosphorylation. Mutations cause autosomal dominant disease through a dominant-negative mechanism. The low pLI score and moderate LOEUF indicate this gene has some tolerance to loss-of-function variants, consistent with the dominant-negative pathogenic mechanism.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
9
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.58
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryNDRG4
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.012
Z-score 3.14
OE 0.32 (0.190.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.57Z-score
OE missense 0.89 (0.801.00)
207 obs / 231.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.190.58)
00.351.4
Missense OE0.89 (0.801.00)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 8 / 24.9Missense obs/exp: 207 / 231.5Syn Z: -0.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedNDRG4-related achromatopsiaOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6939th %ile
GOF
0.6541th %ile
LOF
0.3454th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NDRG4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗