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…

Primary Disease Associations & Inheritance

{Hypertension, essential, salt-sensitive}MIM #145500

Multi

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in ADD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

1,081 rare PASS variants

Rare truncating (LoF)

1 in 790

92 rare PASS variants

Rare synonymous (reference)

1 in 62

362 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADD1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 79	1 in 1,500
South Asian	~43k	1 in 69	1 in 2,700
Remaining (unassigned)	~30k	1 in 58	1 in 1,000
European (Finnish)	~27k	1 in 140	1 in 3,300
Admixed American	~22k	1 in 63	1 in 870
African / African American	~21k	1 in 55	1 in 1,700
East Asian	~20k	1 in 46	1 in 1,700
Ashkenazi Jewish	~13k	1 in 420	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 85	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓