AHSG

protein-coding

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

Gene summary

The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]

MANE transcript

NM_001622.4

Inheritance

ClinVar variants

P:2U:51B:16

Top phenotype

Alopecia-intellectual disability syndrome 1

gnomAD constraint

pLI —, LoF o/e 1.08

Max pathogenic AF

—

Genomic locus

chr3:186,613,060-186,621,318

External References & Databases

Ensembl (ENSG00000145192)

Transcript & Mutation Effects

hg38 • Region Span ~8.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

alopecia-intellectual disability syndrome 1LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0021035

Submitter: PanelApp Australia

alopecia-intellectual disability syndrome 1LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0021035

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Alopecia-intellectual disability syndrome 1AR

Manifestation: Dermatologic; Neurologic

Intervention: General

Rationale: 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

Refs: 28054173

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AHSG variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 57

not providedTotal: 13

Alopecia-intellectual disability syndrome 1Total: 3

AHSG-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001622.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar	1 clinvar	6
missense		1 clinvar	51 clinvar	5 clinvar	5 clinvar	62
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	2	51	10	6	69

Highest pathogenic variant AF is 0.00009418471

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001622.4	RefSeq	NP_001613.2	7	MANE Select
ENST00000411641.7	Ensembl	ENSP00000393887.2	7	MANE Select
NM_001354571.2	RefSeq	NP_001341500.1	7	Standard
NM_001354572.2	RefSeq	NP_001341501.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Post-translational protein phosphorylation
Post-translational protein modification
Metabolism of proteins
Innate Immune System

Biological Process

skeletal system development
ossification
platelet degranulation
pinocytosis
acute-phase response

Molecular Function

cysteine-type endopeptidase inhibitor activity
kinase inhibitor activity

Cellular Component

extracellular region
extracellular space
endoplasmic reticulum lumen
Golgi apparatus
platelet alpha granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000411641
Coding exons: 7
Length: 8396
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125748
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.364	223	208	1.07	0.0000108	2342
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00080	0.00079	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00083	0.00083	rare
European (Non-Finnish)	0.00029	0.00029	rare
South Asian	0.000065	0.000065	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.392

Intolerance Scores

LoFtool: 0.846
RVIS EVS: 0.69
RVIS percentile EVS: 85.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.596

Gene Damage Prediction

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