Auriculocondylar syndrome 4

Summary

Auriculocondylar syndrome 4 (MONDO:0957543) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	auriculocondylar syndrome 4
Mondo ID	MONDO:0957543
OMIM	620457
UMLS	C5830659
MedGen	1841295
GARD	0026862
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ear malformation › auriculocondylar syndrome › auriculocondylar syndrome 4

Related subtypes (5): auriculocondylar syndrome 1, question mark ears, isolated, auriculocondylar syndrome 2, auriculocondylar syndrome 3, auriculocondylar syndrome 2B

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2580891	NC_000007.14:g.18437239_18867540dup	HDAC9	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
HDAC9	Limited	Autosomal dominant	auriculocondylar syndrome 4	2

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
HDAC9	HGNC:14065	ENSG00000048052	Q9UKV0	Histone deacetylase 9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HDAC9	Histone deacetylase 9	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HDAC9	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom

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
monocyte	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HDAC9	277	ubiquitous	marker	oocyte, monocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HDAC9	3,047

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HDAC9	Q9UKV0	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Notch-HLH transcription pathway	1	407.9×	0.006	HDAC9
NOTCH1 Intracellular Domain Regulates Transcription	1	237.9×	0.006	HDAC9
Constitutive Signaling by NOTCH1 PEST Domain Mutants	1	196.9×	0.006	HDAC9
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	1	196.9×	0.006	HDAC9
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.007	HDAC9

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
regulation of striated muscle cell differentiation	1	16852.0×	8e-04	HDAC9
regulation of skeletal muscle fiber development	1	5617.3×	0.001	HDAC9
positive regulation of cell migration involved in sprouting angiogenesis	1	732.7×	0.005	HDAC9
negative regulation of cytokine production	1	510.7×	0.005	HDAC9
B cell activation	1	455.5×	0.005	HDAC9
negative regulation of gene expression, epigenetic	1	401.2×	0.005	HDAC9
epigenetic regulation of gene expression	1	383.0×	0.005	HDAC9
B cell differentiation	1	218.9×	0.008	HDAC9
cellular response to insulin stimulus	1	170.2×	0.009	HDAC9
cholesterol homeostasis	1	156.0×	0.009	HDAC9
heart development	1	78.8×	0.016	HDAC9
inflammatory response	1	37.7×	0.031	HDAC9
negative regulation of DNA-templated transcription	1	31.6×	0.034	HDAC9
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	HDAC9

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HDAC9	CELECOXIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HDAC9	28	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CELECOXIB	4	HDAC9
PHENYLBUTANOIC ACID	4	HDAC9
SODIUM PHENYLBUTYRATE	4	HDAC9
ROMIDEPSIN	4	HDAC9
BELINOSTAT	4	HDAC9
PANOBINOSTAT	4	HDAC9
VORINOSTAT	4	HDAC9
GIVINOSTAT	4	HDAC9
CURCUMIN	3	HDAC9
CAFFEIC ACID	3	HDAC9
PRACINOSTAT	3	HDAC9
TACEDINALINE	3	HDAC9
ENTINOSTAT	3	HDAC9
TUCIDINOSTAT	3	HDAC9
ABEXINOSTAT	3	HDAC9
EBSELEN	3	HDAC9
NANATINOSTAT	2	HDAC9
AR-42	2	HDAC9
CHLOROGENIC ACID	2	HDAC9
DACINOSTAT	2	HDAC9
FIMEPINOSTAT	2	HDAC9
QUISINOSTAT	2	HDAC9
DOMATINOSTAT	2	HDAC9
PYROXAMIDE	1	HDAC9
CUDC-101	1	HDAC9
R-306465	1	HDAC9
GAMMA-AMINOBUTYRIC ACID	1	HDAC9
TRICHOSTATIN	1	HDAC9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HDAC9	1,625	Binding:1612, ADMET:8, Functional:4, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HDAC9	3.5.1.98	histone deacetylase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
HDAC9	1,625

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

28 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)
CELECOXIB	4	HDAC9
PHENYLBUTANOIC ACID	4	HDAC9
SODIUM PHENYLBUTYRATE	4	HDAC9
ROMIDEPSIN	4	HDAC9
BELINOSTAT	4	HDAC9
PANOBINOSTAT	4	HDAC9
VORINOSTAT	4	HDAC9
GIVINOSTAT	4	HDAC9
CURCUMIN	3	HDAC9
CAFFEIC ACID	3	HDAC9
PRACINOSTAT	3	HDAC9
TACEDINALINE	3	HDAC9
ENTINOSTAT	3	HDAC9
TUCIDINOSTAT	3	HDAC9
ABEXINOSTAT	3	HDAC9
EBSELEN	3	HDAC9
NANATINOSTAT	2	HDAC9
AR-42	2	HDAC9
CHLOROGENIC ACID	2	HDAC9
DACINOSTAT	2	HDAC9
FIMEPINOSTAT	2	HDAC9
QUISINOSTAT	2	HDAC9
DOMATINOSTAT	2	HDAC9
PYROXAMIDE	1	HDAC9
CUDC-101	1	HDAC9
R-306465	1	HDAC9
GAMMA-AMINOBUTYRIC ACID	1	HDAC9
TRICHOSTATIN	1	HDAC9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HDAC9
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.