AHSG

alpha 2-HS glycoprotein, the group of Cystatins, type 4

Basic information

Region (hg38): 3:186613059-186621318

Links

ENSG00000145192 ∙ NCBI:197 ∙ OMIM:138680 ∙ HGNC:349 ∙ Uniprot:P02765 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• alopecia-intellectual disability syndrome 1 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alopecia-intellectual disability syndrome 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Neurologic	28054173

ClinVar

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

• Inborn genetic diseases (19 variants)
• not provided (13 variants)
• Alopecia-intellectual disability syndrome 1 (5 variants)
• Leanness, susceptibility to (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AHSG 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				4	2	6
missense			17	3	7	27
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	1	0	17	7	10

Highest pathogenic variant AF is 0.0000789

Variants in AHSG

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

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

Position	Type	Phenotype	Significance	ClinVar
3-186613145-A-T		Alopecia-intellectual disability syndrome 1	Pathogenic (Jan 10, 2020)
3-186613167-G-T		not specified	Uncertain significance (Sep 25, 2023)
3-186613180-C-G		AHSG-related disorder	Benign (Oct 29, 2019)
3-186613222-T-C			Likely benign (Apr 01, 2022)
3-186613230-C-T		not specified	Likely benign (Oct 26, 2021)
3-186613238-G-A		not specified	Uncertain significance (Jul 09, 2021)
3-186613258-A-C		not specified	Uncertain significance (Dec 09, 2023)
3-186613349-C-T			Benign (Mar 15, 2018)
3-186614782-G-A		Leanness, susceptibility to	Benign (Jun 01, 2005)
3-186615691-T-C		not specified	Uncertain significance (Oct 26, 2021)
3-186615694-G-A		not specified	Uncertain significance (Jul 13, 2022)
3-186615743-T-G		not specified	Uncertain significance (Mar 06, 2023)
3-186615763-G-A		not specified	Uncertain significance (Mar 21, 2023)
3-186615775-G-A		not specified	Uncertain significance (Jul 09, 2021)
3-186617180-C-T			Benign (Mar 29, 2018)
3-186617201-G-T			Benign (Jul 13, 2018)
3-186617245-C-T			Likely benign (Apr 13, 2018)
3-186617287-C-T			Benign (Dec 31, 2019)
3-186617313-A-G		not specified	Uncertain significance (Jan 13, 2023)
3-186617318-C-G		not specified	Uncertain significance (Dec 09, 2023)
3-186617320-G-C		not specified	Uncertain significance (Nov 10, 2022)
3-186617342-C-A		not specified	Uncertain significance (Nov 29, 2023)
3-186618238-T-G		Calcium oxalate urolithiasis	association (Mar 01, 2014)
3-186618387-A-G		Calcium oxalate urolithiasis	association (Mar 01, 2014)
3-186618555-A-C		not specified	Uncertain significance (Dec 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AHSG	protein_coding	protein_coding	ENST00000411641	7	8396

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.21e-10	0.0477	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.364	223	208	1.07	0.0000108	2342
Missense in Polyphen		70	62.872	1.1134		734
Synonymous	1.17	74	88.0	0.841	0.00000511	784
Loss of Function	-0.266	14	13.0	1.08	5.49e-7	155

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.000796	0.000794
East Asian	0.000110	0.000109
Finnish	0.000832	0.000832
European (Non-Finnish)	0.000291	0.000290
Middle Eastern	0.000110	0.000109
South Asian	0.0000653	0.0000653
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone. Shows affinity for calcium and barium ions.
• Disease: DISEASE: Alopecia-mental retardation syndrome 1 (APMR1) [MIM:203650]: A rare autosomal recessive form of alopecia. APMR1 patients show loss of hair on the scalp, absence of eyebrows, eyelashes, axillary and pubic hair, and mild to severe mental retardation. {ECO:0000269|PubMed:28054173}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Neutrophil degranulation;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;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;BMP receptor signaling;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.392

Intolerance Scores

• loftool: 0.846
• rvis_EVS: 0.69
• rvis_percentile_EVS: 85.18

Haploinsufficiency Scores

• pHI: 0.472
• hipred: N
• hipred_score: 0.123
• ghis: 0.601

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.596

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ahsg
• Phenotype: growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype; skeleton phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: skeletal system development;ossification;platelet degranulation;pinocytosis;acute-phase response;negative regulation of endopeptidase activity;regulation of bone mineralization;negative regulation of bone mineralization;negative regulation of kinase activity;neutrophil degranulation;post-translational protein modification;cellular protein metabolic process;negative regulation of insulin receptor signaling pathway;regulation of inflammatory response;positive regulation of phagocytosis
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi apparatus;platelet alpha granule lumen;secretory granule lumen;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: cysteine-type endopeptidase inhibitor activity;kinase inhibitor activity