Alopecia, androgenetic, 1

Summary

Alopecia, androgenetic, 1 (MONDO:0007184) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	alopecia, androgenetic, 1
Mondo ID	MONDO:0007184
OMIM	109200
UMLS	C4049090
MedGen	886756
GARD	0024530
Is cancer (heuristic)	no

Also known as: AGA1 · alopecia, androgenetic, 1

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hair anomaly › alopecia › alopecia, isolated › alopecia, androgenetic, 1

Related subtypes (7): alopecia areata 1, familial focal alopecia, alopecia universalis congenita, alopecia, congenital, alopecia, androgenetic, 2, alopecia areata 2, alopecia, androgenetic, 3

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

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1687715	NM_003076.5(SMARCD1):c.1051C>T (p.Arg351Cys)	SMARCD1	Likely pathogenic	no assertion criteria provided
1687627	NM_001453.3(FOXC1):c.1450C>T (p.His484Tyr)	FOXC1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCD1	Orphanet:1465	Coffin-Siris syndrome
FOXC1	Orphanet:250923	Isolated aniridia
FOXC1	Orphanet:708	Peters anomaly
FOXC1	Orphanet:782	Axenfeld-Rieger syndrome
FOXC1	Orphanet:91483	Rieger anomaly
FOXC1	Orphanet:98978	Axenfeld anomaly

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCD1	HGNC:11106	ENSG00000066117	Q96GM5	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1	clinvar
FOXC1	HGNC:3800	ENSG00000054598	Q12948	Forkhead box protein C1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCD1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
FOXC1	Forkhead box protein C1	DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCD1	Other/Unknown	no		SWIB_MDM2_domain, SWIB_domain, SWIB_MDM2_dom_sf
FOXC1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
ventricular zone	1
parotid gland	1
trigeminal ganglion	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCD1	276	ubiquitous	marker	ganglionic eminence, ventricular zone, cortical plate
FOXC1	267	ubiquitous	marker	parotid gland, vena cava, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCD1	3,208
FOXC1	2,896

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCD1	Q96GM5	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FOXC1	Q12948	56.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of intermediate mesoderm	1	713.8×	0.014	FOXC1
Formation of the non-canonical BAF (ncBAF) complex	1	335.9×	0.014	SMARCD1
Formation of the canonical BAF (cBAF) complex	1	317.2×	0.014	SMARCD1
Formation of the polybromo-BAF (pBAF) complex	1	317.2×	0.014	SMARCD1
Formation of the embryonic stem cell BAF (esBAF) complex	1	300.5×	0.014	SMARCD1
Formation of the ureteric bud	1	248.3×	0.014	FOXC1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	228.4×	0.014	SMARCD1
Regulation of endogenous retroelements	1	184.2×	0.015	SMARCD1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	150.3×	0.016	SMARCD1
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.017	SMARCD1
MITF-M-dependent gene expression	1	90.6×	0.022	SMARCD1
RMTs methylate histone arginines	1	73.2×	0.023	SMARCD1
Transcriptional regulation by RUNX1	1	73.2×	0.023	SMARCD1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	58.9×	0.026	SMARCD1
MITF-M-regulated melanocyte development	1	57.1×	0.026	SMARCD1
Chromatin organization	1	40.8×	0.034	SMARCD1
Chromatin modifying enzymes	1	36.1×	0.034	SMARCD1
Epigenetic regulation of gene expression	1	35.7×	0.034	SMARCD1
RNA Polymerase II Transcription	1	11.3×	0.101	SMARCD1
Gene expression (Transcription)	1	8.9×	0.120	SMARCD1
Generic Transcription Pathway	1	7.5×	0.134	SMARCD1
Developmental Biology	1	7.2×	0.134	SMARCD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glomerular epithelium development	1	8426.0×	0.003	FOXC1
positive regulation of hematopoietic stem cell differentiation	1	8426.0×	0.003	FOXC1
apoptotic process involved in outflow tract morphogenesis	1	4213.0×	0.003	FOXC1
negative regulation of apoptotic process involved in outflow tract morphogenesis	1	4213.0×	0.003	FOXC1
positive regulation of core promoter binding	1	4213.0×	0.003	FOXC1
negative regulation of lymphangiogenesis	1	2808.7×	0.004	FOXC1
positive regulation of hematopoietic progenitor cell differentiation	1	2808.7×	0.004	FOXC1
paraxial mesoderm formation	1	1685.2×	0.005	FOXC1
mesenchymal cell development	1	1203.7×	0.005	FOXC1
glycosaminoglycan metabolic process	1	1203.7×	0.005	FOXC1
lacrimal gland development	1	1053.2×	0.005	FOXC1
maintenance of lens transparency	1	1053.2×	0.005	FOXC1
regulation of organ growth	1	1053.2×	0.005	FOXC1
lymph vessel development	1	936.2×	0.005	FOXC1
primordial germ cell migration	1	936.2×	0.005	FOXC1
positive regulation of DNA binding	1	601.9×	0.007	FOXC1
vascular endothelial growth factor signaling pathway	1	526.6×	0.008	FOXC1
cellular response to chemokine	1	495.6×	0.008	FOXC1
nucleosome disassembly	1	401.2×	0.008	SMARCD1
neural crest cell development	1	401.2×	0.008	FOXC1
positive regulation of keratinocyte differentiation	1	401.2×	0.008	FOXC1
negative regulation of mitotic cell cycle	1	401.2×	0.008	FOXC1
embryonic heart tube development	1	383.0×	0.008	FOXC1
ventricular cardiac muscle tissue morphogenesis	1	351.1×	0.008	FOXC1
cellular response to fatty acid	1	351.1×	0.008	SMARCD1
artery morphogenesis	1	337.0×	0.008	FOXC1
regulation of G0 to G1 transition	1	337.0×	0.008	SMARCD1
blood vessel diameter maintenance	1	312.1×	0.008	FOXC1
regulation of nucleotide-excision repair	1	300.9×	0.008	SMARCD1
cardiac muscle cell proliferation	1	290.6×	0.008	FOXC1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMARCD1	1	2
FOXC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SMARCD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCD1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	SMARCD1

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	1	SMARCD1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FOXC1

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)
FOXC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.