DAAM2

Chr 6AR

dishevelled associated activator of morphogenesis 2

Also known as: NPHS24, dJ90A20A.1

NCBI Gene: 23500ENSG00000146122UniProt: Q86T65

Predicted to enable actin binding activity and small GTPase binding activity. Involved in several processes, including podocyte cell migration; regulation of actin filament polymerization; and regulation of filopodium assembly. Located in extracellular exosome. Implicated in familial nephrotic syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Nephrotic syndrome, type 24MIM #619263
AR
270
ClinVar variants
11
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DAAM2
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Gene-Disease Validity (ClinGen)
idiopathic multidrug-resistant nephrotic syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
11 Pathogenic / Likely Pathogenic· 194 VUS of 270 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.09LOEUF
pLI 1.000
Z-score 6.45
OE 0.02 (0.01–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.27Z-score
OE missense 0.86 (0.80–0.92)
535 obs / 624.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.01–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.80–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 1 / 50.4Missense obs/exp: 535 / 624.5Syn Z: 0.80

ClinVar Variant Classifications

270 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS194
Likely Benign41
Benign23
Conflicting1
9
Pathogenic
2
Likely Pathogenic
194
VUS
41
Likely Benign
23
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
7
0
9
Likely Pathogenic
0
0
2
0
2
VUS
1
178
15
0
194
Likely Benign
1
13
11
16
41
Benign
0
9
7
7
23
Conflicting
—1
Total22024223270

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

View in ClinVar →

Protein Context — Lollipop Plot

DAAM2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Nephrotic syndrome, type 24

MIM #619263

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An atlas of genetic influences on osteoporosis in humans and mice.
Morris JA et al.·Nat Genet
2019
The prognostic value of DAAM2 in lower grade glioma, liver cancer, and breast cancer.
Li Z et al.·Clin Transl Oncol
2023
The Daam2-VHL-Nedd4 axis governs developmental and regenerative oligodendrocyte differentiation.
Ding X et al.·Genes Dev
2020
Short stature and dysmorphic features in Asian Indian siblings with DAAM2-associated steroid-resistant nephrotic syndrome: Expansion of the phenotypic spectrum or a blended phenotype?
Pragna Lakshmi T et al.·Clin Genet
2024Case report
Correlation Between Daam2 Expression Changes and Demyelination in Guillain-Barre Syndrome.
Cui Q et al.·Cell Mol Neurobiol
2016
DAAM2 polymorphism is closely related to the clinical outcomes of allogeneic hematopoietic stem cell transplantation.
Yi HG et al.·Ann Hematol
2012
Construction of a four-mRNA prognostic signature with its ceRNA network in CESC.
Li L et al.·Sci Rep
2022
Minimalistic transcriptomic signatures permit accurate early prediction of COVID-19 mortality.
Narendra R et al.·JCI Insight
2025
Rare Variants in Known Susceptibility Loci and Their Contribution to Risk of Lung Cancer.
Liu Y et al.·J Thorac Oncol
2018
Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis.
Kim M et al.·Endocrinol Metab (Seoul)
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools