ADD1

Chr 4Multi

adducin 1

Also known as: ADDA

NCBI Gene: 118ENSG00000087274UniProt: P35611

The alpha-adducin protein promotes assembly of the spectrin-actin cytoskeletal network and binds to calmodulin, serving as a key membrane-cytoskeleton-associated protein. Mutations cause salt-sensitive essential hypertension with multifactorial inheritance. This gene is highly constrained against loss-of-function variants in the general population.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

{Hypertension, essential, salt-sensitive}MIM #145500
Multi
1
Active trials
16
Pubs (1 yr)
0
P/LP submissions
—
P/LP missense
0.30
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— ADD1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.988
Z-score 4.74
OE 0.14 (0.07–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.80Z-score
OE missense 0.89 (0.82–0.97)
401 obs / 449.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.07–0.30)
0≤0.351.4
Missense OE0.89 (0.82–0.97)
0≤0.61.4
Synonymous OE0.88
0≤1.21.6
LoF obs/exp: 5 / 35.5Missense obs/exp: 401 / 449.0Syn Z: 1.30
DN
0.4685th %ile
GOF
0.5072th %ile
LOF
0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.30

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ADD1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ICAM1 778G>A (rs1799969), ADD1 1378G>T (rs4961), NPPA 553T>C (rs5065), and NOS3 894G>T (rs1799983) Variants in Infants with Gastroschisis from Western Mexico.
Bobadilla Morales L et al.·Genet Test Mol Biomarkers
2025
Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss.
Akın V et al.·J Otol
2024Open Access
Mechanisms of Regulation of the CHRDL1 Gene by the TWIST2 and ADD1/SREBP1c Transcription Factors.
Casasnovas-Nieves JJ et al.·Genes (Basel)
2023Open AccessFunctional
Cathepsin B S-nitrosylation promotes ADAR1-mediated editing of its own mRNA transcript via an ADD1/MATR3 regulatory axis.
Lin Z et al.·Cell Res
2023
ADD1 Single Nucleotide Polymorphisms Are Associated With Essential Hypertension Among Han and Mongolian Population in Inner Mongolia Area.
Zhang Y et al.·Front Genet
2022Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients