Alopecia-intellectual disability syndrome 1

Summary

Alopecia-intellectual disability syndrome 1 (MONDO:0021035) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	alopecia-intellectual disability syndrome 1
Mondo ID	MONDO:0021035
OMIM	203650
DOID	DOID:0080628
UMLS	C1859878
MedGen	349263
GARD	0025277
Is cancer (heuristic)	no

Also known as: alopecia-intellectual disability syndrome 1 · alopecia-mental retardation syndrome 1 · APMR · APMR1

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › alopecia - intellectual disability syndrome › alopecia-intellectual disability syndrome 1

Related subtypes (3): alopecia-intellectual disability syndrome 2, alopecia-intellectual disability syndrome 3, alopecia-intellectual disability syndrome 4

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

3 benign, 1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
488189	NM_001622.4(AHSG):c.950G>A (p.Arg317His)	AHSG	Likely pathogenic	criteria provided, single submitter
1029361	NM_001622.4(AHSG):c.4A>T (p.Lys2Ter)	AHSG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032762	NM_001622.4(AHSG):c.1024G>A (p.Val342Met)	AHSG	Uncertain significance	criteria provided, multiple submitters, no conflicts
1188909	NM_001622.4(AHSG):c.810A>C (p.Thr270=)	AHSG	Benign	criteria provided, multiple submitters, no conflicts
16043	NM_001622.4(AHSG):c.743T>C (p.Met248Thr)	AHSG	Benign	criteria provided, multiple submitters, no conflicts
16044	NM_001622.4(AHSG):c.767G>C (p.Ser256Thr)	AHSG	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
AHSG	Limited	Autosomal recessive	alopecia-intellectual disability syndrome 1	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AHSG	Orphanet:2850	Alopecia-intellectual disability syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AHSG	HGNC:349	ENSG00000145192	P02765	Alpha-2-HS-glycoprotein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AHSG	Alpha-2-HS-glycoprotein	Promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AHSG	Other/Unknown	no		Cystatin_dom, Prot_inh_fetuin_CS, Cystatin_Fetuin_A

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AHSG	125	tissue_specific	marker	liver, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AHSG	3,426

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AHSG	P02765	77.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Post-translational protein phosphorylation	1	100.2×	0.015	AHSG
Platelet degranulation	1	87.8×	0.015	AHSG
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.015	AHSG
Neutrophil degranulation	1	23.1×	0.043	AHSG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pinocytosis	1	4213.0×	0.002	AHSG
negative regulation of bone mineralization	1	936.2×	0.004	AHSG
regulation of bone mineralization	1	732.7×	0.004	AHSG
acute-phase response	1	421.3×	0.005	AHSG
negative regulation of insulin receptor signaling pathway	1	374.5×	0.005	AHSG
positive regulation of phagocytosis	1	318.0×	0.005	AHSG
ossification	1	227.7×	0.006	AHSG
regulation of inflammatory response	1	168.5×	0.007	AHSG
skeletal system development	1	125.8×	0.008	AHSG

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AHSG	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AHSG	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	AHSG

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
AHSG	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.