ALB

albumin

Basic information

Region (hg38): 4:73397113-73421482

Links

ENSG00000163631 ∙ NCBI:213 ∙ OMIM:103600 ∙ HGNC:399 ∙ Uniprot:P02768 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital analbuminemia (Supportive), mode of inheritance: AR
• hyperthyroxinemia, familial dysalbuminemic (Limited), mode of inheritance: AD
• congenital analbuminemia (Definitive), mode of inheritance: AR
• congenital analbuminemia (Strong), mode of inheritance: AR
• hyperthyroxinemia, familial dysalbuminemic (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperthyroxinemia, familial dysalbuminemic; Analbuminemia	AD/AR	Endocrine; Pharmacogenomic; Renal	In Dysalbuminemic hyperthyroxinemia, genetic diagnosis may help avoid unecessary treatment; In Analbuminemia, medical treatment of sequelae of low albumin (eg, dysplipidemia) can be beneficial, and precautions with certain medications may be indicated	Endocrine; Musculoskeletal; Renal	13673098; 13785411; 14187073; 5926635; 1269174; 2430733; 3578276; 3407659; 3353369; 2762316; 2404284; 2104980; 6310605; 7829599; 8048949; 8064810; 8621984; 9329347; 9589637; 10842774; 10946882; 11781148; 12099390; 12743361; 15541334; 15300429; 16183048; 15996651; 18459107; 20638375; 20415703; 22327004; 22227324
Depending on the disorder, manifestations may primarily affect the endocrine system (as in Dysalbuminemic hyperthyroxinemia) or may result in findings such as edema and hypercholesterolemia, as well as pharmacogenomic implications (as in Analbuminemia)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALB gene.

• Hyperthyroxinemia, familial dysalbuminemic (54 variants)
• not provided (40 variants)
• Alloalbuminemia (10 variants)
• Analbuminemia (10 variants)
• Inborn genetic diseases (5 variants)
• ALBUMIN IOWA CITY 1 (1 variants)
• not specified (1 variants)
• ALBUMIN CASEBROOK (1 variants)
• - (1 variants)
• ALBUMIN NAGASAKI 2 (1 variants)
• PROALBUMIN MALMO (1 variants)
• ALBUMIN MEXICO 2 (1 variants)
• ALBUMIN TRADATE 2 (1 variants)
• ALBUMIN TAGLIACOZZO (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	5	5	16
missense			31	2	2	35
nonsense	1					1
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region			2		4	6
non coding			5	4	5	14
Total	3	1	42	11	12

Highest pathogenic variant AF is 0.0000460

Variants in ALB

This is a list of pathogenic ClinVar variants found in the ALB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-73404283-T-C		Hyperthyroxinemia, dysalbuminemic	Uncertain significance (Jun 14, 2016)
4-73404315-C-T		Hyperthyroxinemia, familial dysalbuminemic	Likely benign (Jan 13, 2018)
4-73404394-C-T		PROALBUMIN MALMO • Hyperthyroxinemia, familial dysalbuminemic	Uncertain significance (Apr 27, 2017)
4-73404395-G-A		PROALBUMIN LILLE	other (Jul 18, 2019)
4-73404398-G-A		Ehlers-Danlos syndrome, arthrochalasia type	Pathogenic (Aug 04, 1993)
4-73404398-G-C		Alloalbuminemia	Pathogenic (Jul 01, 1987)
4-73404398-G-T		PROALBUMIN JAFFNA	other (Jul 18, 2019)
4-73404401-A-T		Alloalbuminemia	Pathogenic (Nov 01, 1991)
4-73404406-C-T		ALBUMIN LARINO	other (Jul 18, 2019)
4-73404407-G-A		Analbuminemia Baghdad	Pathogenic (Jan 02, 2002)
4-73405116-A-C			Uncertain significance (Jan 16, 2023)
4-73405117-C-A			Uncertain significance (May 23, 2023)
4-73405145-G-A		Hyperthyroxinemia, familial dysalbuminemic	Uncertain significance (Jan 13, 2018)
4-73405147-T-C			Likely benign (Nov 17, 2022)
4-73405177-A-C		Hyperthyroxinemia, familial dysalbuminemic	Uncertain significance (Jan 13, 2018)
4-73406657-C-T		Analbuminemia	Pathogenic (Mar 15, 1994)
4-73406718-CAT-C		Analbuminemia	Pathogenic (Jun 29, 2023)
4-73406722-T-C		Hyperthyroxinemia, familial dysalbuminemic	Uncertain significance (Jan 13, 2018)
4-73406739-C-G		Hyperthyroxinemia, familial dysalbuminemic • Inborn genetic diseases	Uncertain significance (Mar 31, 2023)
4-73406739-C-T		Hyperthyroxinemia, familial dysalbuminemic	Benign (Jan 13, 2018)
4-73406741-G-A		ALBUMIN TORINO	other (Jul 18, 2019)
4-73406750-G-A		ALBUMIN MALMO-95	other (Jul 18, 2019)
4-73406760-T-C		Hyperthyroxinemia, familial dysalbuminemic	Pathogenic (May 01, 1998)
4-73408586-C-T		Hyperthyroxinemia, familial dysalbuminemic	Benign (Jan 22, 2024)
4-73408595-A-G			Uncertain significance (May 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALB	protein_coding	protein_coding	ENST00000295897	14	24299

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.643	0.357	125719	0	28	125747	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.656	288	321	0.897	0.0000169	4020
Missense in Polyphen		59	87.526	0.67409		1154
Synonymous	-0.915	129	116	1.11	0.00000632	1096
Loss of Function	4.29	7	34.0	0.206	0.00000191	441

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc. {ECO:0000269|PubMed:19021548}.
• Disease: DISEASE: Hyperthyroxinemia, familial dysalbuminemic (FDAH) [MIM:615999]: A disorder characterized by abnormally elevated levels of total serum thyroxine (T4) in euthyroid patients. It is due to abnormal serum albumin that binds T4 with enhanced affinity. {ECO:0000269|PubMed:7852505, ECO:0000269|PubMed:8048949, ECO:0000269|PubMed:9329347, ECO:0000269|PubMed:9589637}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Analbuminemia (ANALBA) [MIM:616000]: A rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. Affected individuals manifest mild edema, hypotension, fatigue, and, occasionally, lower body lipodystrophy (mainly in adult females). The most common biochemical finding is hyperlipidemia, with a significant increase in the total and LDL cholesterol concentrations, but normal concentrations of HDL cholesterol and triglycerides. {ECO:0000269|PubMed:8134387}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thyroid hormone synthesis - Homo sapiens (human);Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;Human Complement System;Vesicle-mediated transport;Post-translational protein phosphorylation;HDL remodeling;Metabolism of lipids;Post-translational protein modification;Metabolism of proteins;Metabolism;Recycling of bile acids and salts;Bile acid and bile salt metabolism;Transport of vitamins, nucleosides, and related molecules;SLC-mediated transmembrane transport;Transport of small molecules;Metabolism of steroids;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;EGFR1;Hemostasis;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling;Scavenging of heme from plasma;Binding and Uptake of Ligands by Scavenger Receptors;Transport of organic anions;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.958

Intolerance Scores

• loftool: 0.648
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.37

Haploinsufficiency Scores

• pHI: 0.843
• hipred: N
• hipred_score: 0.495
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.525

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Alb
• Phenotype: digestive/alimentary phenotype; renal/urinary system phenotype; liver/biliary system phenotype; endocrine/exocrine gland phenotype; neoplasm; normal phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: retina homeostasis;platelet degranulation;receptor-mediated endocytosis;cellular response to starvation;hemolysis by symbiont of host erythrocytes;high-density lipoprotein particle remodeling;negative regulation of apoptotic process;negative regulation of programmed cell death;post-translational protein modification;cellular protein metabolic process;maintenance of mitochondrion location;cellular oxidant detoxification
• Cellular component: extracellular region;extracellular space;nucleus;endoplasmic reticulum;endoplasmic reticulum lumen;Golgi apparatus;platelet alpha granule lumen;protein-containing complex;myelin sheath;extracellular exosome;blood microparticle
• Molecular function: DNA binding;fatty acid binding;copper ion binding;protein binding;drug binding;toxic substance binding;antioxidant activity;oxygen binding;pyridoxal phosphate binding;identical protein binding;chaperone binding