ALB

Chr 4ADAR

albumin

Also known as: FDAHT, HSA, PRO0883, PRO0903, PRO1341

NCBI Gene: 213 ENSG00000163631 UniProt: Q8TES7 OMIM: 103600

Albumin regulates blood plasma colloid osmotic pressure and serves as a carrier protein for hormones, fatty acids, metabolites, and drugs. Mutations cause analbuminemia, dysalbuminemic hyperthyroxinemia, and dysalbuminemic hypertriiodothyroninemia with both autosomal dominant and autosomal recessive inheritance patterns. The gene shows significant constraint against loss-of-function variants, indicating its essential physiological role.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the most abundant protein in human blood. This protein functions in the regulation of blood plasma colloid osmotic pressure and acts as a carrier protein for a wide range of endogenous molecules including hormones, fatty acids, and metabolites, as well as exogenous drugs. Additionally, this protein exhibits an esterase-like activity with broad substrate specificity. The encoded preproprotein is proteolytically processed to generate the mature protein. A peptide derived from this protein, EPI-X4, is an endogenous inhibitor of the CXCR4 chemokine receptor. [provided by RefSeq, Jul 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?[Dysalbuminemic hypertriiodothyroninemia]MIM #615999

ADAR

[Dysalbuminemic hyperthyroxinemia]MIM #615999

ADAR

AnalbuminemiaMIM #616000

Clinical highlights

Gene–disease validity (ClinGen)

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

2005

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.643

Z-score 4.29

OE 0.21 (0.12–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.66Z-score

OE missense 0.90 (0.81–0.99)

288 obs / 321.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.12–0.39)

0≤0.351.4

Missense OE?0.90 (0.81–0.99)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 7 / 34.0Missense obs/exp: 288 / 321.1Syn Z: -0.92

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

762 rare PASS variants

Rare truncating (LoF)

1 in 1,900

102 rare PASS variants

Rare synonymous (reference)

1 in 140

264 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ALB. 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 93	1 in 1,800
South Asian	~43k	1 in 110	1 in 1,100
Remaining (unassigned)	~30k	1 in 85	1 in 2,700
European (Finnish)	~27k	1 in 270	1 in 5,300
Admixed American	~22k	1 in 73	1 in 3,200
African / African American	~21k	1 in 95	1 in 1,900
East Asian	~20k	1 in 89	1 in 1,300
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 77	≈ 1 in 2,900

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 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓