IGFALS

insulin like growth factor binding protein acid labile subunit

Basic information

Region (hg38): 16:1790413-1794971

Links

ENSG00000099769 ∙ NCBI:3483 ∙ OMIM:601489 ∙ HGNC:5468 ∙ Uniprot:P35858 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short stature due to primary acid-labile subunit deficiency (Strong), mode of inheritance: AR
• short stature due to primary acid-labile subunit deficiency (Supportive), mode of inheritance: AR
• short stature due to primary acid-labile subunit deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Insulin-like growth factor-binding protein, acid-labile subunit, deficiency of	AR	Endocrine	As growth hormone treatment has not been reported as being effective in this condition, genetic diagnosis may be beneficial in terms of pursuing optimal management	Endocrine	14762184; 17726072; 21396577; 21664162; 23488611

ClinVar

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

• Inborn_genetic_diseases (143 variants)
• Short_stature_due_to_primary_acid-labile_subunit_deficiency (70 variants)
• not_provided (68 variants)
• not_specified (27 variants)
• IGFALS-related_disorder (15 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IGFALS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004970.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			11	22	8	41
missense	1	1	174	18	2	196
nonsense		2	3			5
start loss		1				1
frameshift	2	2	1			5
splice donor/acceptor (+/-2bp)						0
Total	3	6	189	40	10

Highest pathogenic variant AF is 0.0000361449

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IGFALS	protein_coding	protein_coding	ENST00000415638	2	4559

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.44e-11	0.0170	125160	0	53	125213	0.000212

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.22	479	409	1.17	0.0000327	3959
Missense in Polyphen		152	131.51	1.1558		1508
Synonymous	-2.15	252	212	1.19	0.0000171	1456
Loss of Function	-0.843	14	11.0	1.27	5.67e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000473	0.000473
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000163
Finnish	0.000188	0.000139
European (Non-Finnish)	0.000153	0.000142
Middle Eastern	0.000167	0.000163
South Asian	0.000395	0.000392
Other	0.000525	0.000491

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in protein-protein interactions that result in protein complexes, receptor-ligand binding or cell adhesion.
• Pathway: Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (Consensus)

Recessive Scores

• pRec: 0.442

Intolerance Scores

• loftool: 0.542
• rvis_EVS: -0.88
• rvis_percentile_EVS: 10.5

Haploinsufficiency Scores

• pHI: 0.129
• hipred: N
• hipred_score: 0.306
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.704

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Igfals
• Phenotype: reproductive system phenotype; skeleton phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: cell adhesion;signal transduction;cellular protein metabolic process
• Cellular component: extracellular region;extracellular space;nucleoplasm;extracellular matrix;insulin-like growth factor ternary complex;extracellular exosome
• Molecular function: insulin-like growth factor binding