ADD1

Chr 4Multi

adducin 1

Also known as: ADDA

NCBI Gene: 118 ENSG00000087274 UniProt: P35611 OMIM: 102680

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Adducins are a family of cytoskeletal proteins encoded by three genes (alpha, beta, and gamma). Adducin acts as a heterodimer of the related alpha, beta, or gamma subunits. The protein encoded by this gene represents the alpha subunit. Alpha- and beta-adducin include a protease-resistant N-terminal region and a protease-sensitive, hydrophilic C-terminal region. Adducin binds with high affinity to Ca(2+)/calmodulin and is a substrate for protein kinases A and C. [provided by RefSeq, Aug 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismMultiLOEUF 0.301 OMIM phenotype

Clinical Summary— ADD1

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 85 VUS of 124 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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 OE?0.14 (0.07–0.30)

0≤0.351.4

Missense OE?0.89 (0.82–0.97)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 5 / 35.5Missense obs/exp: 401 / 449.0Syn Z: 1.30

This gene — mechanism propensity

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

124 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS85

Likely Benign8

Benign7

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	85	0	0	85
Likely Benign	2	1	5	8
Benign	1	0	6	7
Total	89	1	11	101

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

View in ClinVar →

135 pathogenic / likely-pathogenic (of 147) ClinVar copy-number / structural variants overlap ADD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →