Otopalatodigital syndrome type 2

Summary

Otopalatodigital syndrome type 2 (MONDO:0010571) is a disease caused by FLNA (GenCC Definitive), with 7 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FLNA (GenCC Definitive)
• Cohort genes: 7
• ClinVar variants: 3,164
• Phenotypes (HPO): 55

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

55 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000160	Narrow mouth	Very frequent (80-99%)
HP:0000175	Cleft palate	Very frequent (80-99%)
HP:0000239	Large fontanelles	Very frequent (80-99%)
HP:0000272	Malar flattening	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000336	Prominent supraorbital ridges	Very frequent (80-99%)
HP:0000337	Broad forehead	Very frequent (80-99%)
HP:0000365	Hearing impairment	Very frequent (80-99%)
HP:0000369	Low-set ears	Very frequent (80-99%)
HP:0000377	Abnormal pinna morphology	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000674	Anodontia	Very frequent (80-99%)
HP:0000677	Oligodontia	Very frequent (80-99%)
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0002089	Pulmonary hypoplasia	Very frequent (80-99%)
HP:0002652	Skeletal dysplasia	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0006487	Bowing of the long bones	Very frequent (80-99%)
HP:0009778	Short thumb	Very frequent (80-99%)
HP:0010109	Short hallux	Very frequent (80-99%)
HP:0000047	Hypospadias	Frequent (30-79%)
HP:0000126	Hydronephrosis	Frequent (30-79%)
HP:0000162	Glossoptosis	Frequent (30-79%)
HP:0000201	Pierre-Robin sequence	Frequent (30-79%)
HP:0000238	Hydrocephalus	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000772	Abnormal rib morphology	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001321	Cerebellar hypoplasia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001539	Omphalocele	Frequent (30-79%)
HP:0001654	Abnormal heart valve morphology	Frequent (30-79%)
HP:0001671	Abnormal cardiac septum morphology	Frequent (30-79%)
HP:0002684	Thickened calvaria	Frequent (30-79%)
HP:0002738	Hypoplastic frontal sinuses	Frequent (30-79%)
HP:0002869	Flared iliac wings	Frequent (30-79%)
HP:0002990	Fibular aplasia	Frequent (30-79%)
HP:0003042	Elbow dislocation	Frequent (30-79%)
HP:0004279	Short palm	Frequent (30-79%)
HP:0005640	Abnormal vertebral segmentation and fusion	Frequent (30-79%)
HP:0005916	Abnormal metacarpal morphology	Frequent (30-79%)
HP:0006000	Ureteral obstruction	Frequent (30-79%)
HP:0011001	Increased bone mineral density	Frequent (30-79%)
HP:0100490	Camptodactyly of finger	Frequent (30-79%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0001087	Developmental glaucoma	Occasional (5-29%)
HP:0002084	Encephalocele	Occasional (5-29%)
HP:0002475	Myelomeningocele	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	otopalatodigital syndrome type 2
Mondo ID	MONDO:0010571
MeSH	C538089
OMIM	304120
Orphanet	90652
DOID	DOID:0111784
ICD-11	1897308206
SNOMED CT	42432003
UMLS	C1844696
MedGen	337064
GARD	0005802
NORD	1539
Is cancer (heuristic)	no

Also known as: Andre syndrome · cranio-oro-digital syndrome · FPO · OPD 2 syndrome · OPD II syndrome · OPD syndrome 2 · OPD2 · oto-palato-digital syndrome type 2 · Otopalatodigital Syndrome Type I and II · otopalatodigital syndrome, type II · otopalatodigital syndrome, type II, X-linked dominant

Data availability: 3,164 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › filamin-related bone disorder › otopalatodigital syndrome spectrum disorder › otopalatodigital syndrome › otopalatodigital syndrome type 2

Related subtypes (1): otopalatodigital syndrome type 1

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

600 retrieved; paginated sample, class counts are floors:

199 uncertain significance, 198 likely benign, 108 conflicting classifications of pathogenicity, 35 benign, 27 pathogenic, 21 benign/likely benign, 7 pathogenic/likely pathogenic, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1455467	NC_000023.10:g.(?153599231)(153609567_?)del	EMD	Pathogenic	criteria provided, single submitter
1066948	NM_001110556.2(FLNA):c.1066-1G>A	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069630	NM_001110556.2(FLNA):c.334_335insGAGAACGTGTCGG (p.Glu112fs)	FLNA	Pathogenic	criteria provided, single submitter
1070215	NM_001110556.2(FLNA):c.812del (p.Pro271fs)	FLNA	Pathogenic	criteria provided, single submitter
1070361	NM_001110556.2(FLNA):c.2947dup (p.Val983fs)	FLNA	Pathogenic	criteria provided, single submitter
1071106	NM_001110556.2(FLNA):c.6677dup (p.Gln2227fs)	FLNA	Pathogenic	criteria provided, single submitter
1071650	NM_001110556.2(FLNA):c.829_835del (p.Arg276_Pro277insTer)	FLNA	Pathogenic	criteria provided, single submitter
1072111	NM_001110556.2(FLNA):c.577C>T (p.Gln193Ter)	FLNA	Pathogenic	criteria provided, single submitter
1072754	NM_001110556.2(FLNA):c.6329_6330del (p.Glu2110fs)	FLNA	Pathogenic	criteria provided, single submitter
1073243	NM_001110556.2(FLNA):c.5146del (p.Gln1716fs)	FLNA	Pathogenic	criteria provided, single submitter
1075551	NM_001110556.2(FLNA):c.2965C>T (p.Gln989Ter)	FLNA	Pathogenic	criteria provided, single submitter
1075693	NM_001110556.2(FLNA):c.4138dup (p.Thr1380fs)	FLNA	Pathogenic	criteria provided, single submitter
11754	NM_001110556.2(FLNA):c.245A>T (p.Glu82Val)	FLNA	Pathogenic	criteria provided, single submitter
11755	NM_001110556.2(FLNA):c.620C>T (p.Pro207Leu)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11756	NM_001110556.2(FLNA):c.760G>A (p.Glu254Lys)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11758	NM_001110556.2(FLNA):c.3562G>A (p.Ala1188Thr)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11759	NM_001110556.2(FLNA):c.3596C>T (p.Ser1199Leu)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11761	NM_001110556.2(FLNA):c.3557C>T (p.Ser1186Leu)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11773	NM_001110556.2(FLNA):c.629G>T (p.Cys210Phe)	FLNA	Pathogenic	no assertion criteria provided
11775	NM_001110556.2(FLNA):c.5217G>A (p.Thr1739=)	FLNA	Pathogenic	criteria provided, multiple submitters, no conflicts
11777	NM_001110556.2(FLNA):c.862G>A (p.Gly288Arg)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1254666	NM_001110556.2(FLNA):c.257AGA[2] (p.Lys88del)	FLNA	Pathogenic	criteria provided, multiple submitters, no conflicts
1383677	NM_001110556.2(FLNA):c.6318C>G (p.Tyr2106Ter)	FLNA	Pathogenic	criteria provided, single submitter
1399735	NM_001110556.2(FLNA):c.7285_7286dup (p.Gly2430fs)	FLNA	Pathogenic	criteria provided, single submitter
1407335	NM_001110556.2(FLNA):c.2191_2192insGT (p.Tyr731fs)	FLNA	Pathogenic	criteria provided, single submitter
1429750	NM_001110556.2(FLNA):c.1759G>T (p.Glu587Ter)	FLNA	Pathogenic	criteria provided, single submitter
1434332	NM_001110556.2(FLNA):c.2751_2752dup (p.Asp918fs)	FLNA	Pathogenic	criteria provided, single submitter
1444364	NM_001110556.2(FLNA):c.1112_1113dup (p.Val372fs)	FLNA	Pathogenic	criteria provided, single submitter
1451173	NM_001110556.2(FLNA):c.656del (p.Ser219fs)	FLNA	Pathogenic	criteria provided, single submitter
1452088	NM_001110556.2(FLNA):c.2963_2964del (p.Asp988fs)	FLNA	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 30 · Orphanet: 18 · 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
FLNA	Definitive	X-linked	otopalatodigital syndrome type 2	30

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FLNA	Orphanet:1826	Frontometaphyseal dysplasia
FLNA	Orphanet:2301	Congenital short bowel syndrome
FLNA	Orphanet:2484	Melnick-Needles syndrome
FLNA	Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome
FLNA	Orphanet:555877	FLNA-related X-linked myxomatous valvular dysplasia
FLNA	Orphanet:75497	X-linked Ehlers-Danlos syndrome
FLNA	Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome
FLNA	Orphanet:90650	Otopalatodigital syndrome type 1
FLNA	Orphanet:90652	Otopalatodigital syndrome type 2
FLNA	Orphanet:98892	Periventricular nodular heterotopia
FLNA	Orphanet:99811	Neuronal intestinal pseudoobstruction
EMD	Orphanet:98863	X-linked Emery-Dreifuss muscular dystrophy
HCFC1	Orphanet:369962	Methylmalonic acidemia with homocystinuria, type cblX
HCFC1	Orphanet:777	X-linked non-syndromic intellectual disability
ABCD1	Orphanet:139396	X-linked cerebral adrenoleukodystrophy
ABCD1	Orphanet:139399	Adrenomyeloneuropathy
ABCD1	Orphanet:369942	CADDS
ABCD1	Orphanet:388	Hirschsprung disease

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	gencc,clinvar
OPN1MW2	HGNC:26952	ENSG00000166160	P0DN77	Medium-wave-sensitive opsin 2	clinvar
DNASE1L1	HGNC:2957	ENSG00000013563	P49184	Deoxyribonuclease-1-like 1	clinvar
EMD	HGNC:3331	ENSG00000102119	P50402	Emerin	clinvar
HCFC1	HGNC:4839	ENSG00000172534	P51610	Host cell factor 1	clinvar
ABCD1	HGNC:61	ENSG00000101986	P33897	ATP-binding cassette sub-family D member 1	clinvar
ARHGAP4	HGNC:674	ENSG00000089820	P98171	Rho GTPase-activating protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.
OPN1MW2	Medium-wave-sensitive opsin 2	Visual pigments are the light-absorbing molecules that mediate vision.
EMD	Emerin	Stabilizes and promotes the formation of a nuclear actin cortical network.
HCFC1	Host cell factor 1	Transcriptional coregulator.
ABCD1	ATP-binding cassette sub-family D member 1	ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen.
ARHGAP4	Rho GTPase-activating protein 4	Inhibitory effect on stress fiber organization.

Protein-family classification

Druggable: 5 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.71

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
Antibody/Immunoglobulin	2	8.3×	0.132
Phosphatase	1	12.0×	0.173
Transporter	1	11.1×	0.173
GPCR	1	3.4×	0.387
Scaffold/PPI	1	2.5×	0.409
Other/Unknown	1	0.3×	0.997

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
OPN1MW2	GPCR	yes		GPCR_Rhodpsn, Opsin_red/grn, Opsin
DNASE1L1	Phosphatase	yes		Endo/exonuclease/phosphatase, DNase_I, Deoxyribonuclease-1_AS
EMD	Other/Unknown	no		LEM_dom, LEM/LEM-like_dom_sf, LEM_emerin
HCFC1	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, Kelch-typ_b-propeller
ABCD1	Transporter	yes	7.6.2.4	ABC_transporter-like_ATP-bd, AAA+_ATPase, FA_transporter
ARHGAP4	Scaffold/PPI	no		RhoGAP_dom, FCH_dom, SH3_domain

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
popliteal artery	2
right coronary artery	1
tibial artery	1
colonic epithelium	1
primordial germ cell in gonad	1
ventricular zone	1
gastrocnemius	1
gluteal muscle	1
hindlimb stylopod muscle	1
left ovary	1
left uterine tube	1
parotid gland	1
skeletal muscle tissue of rectus abdominis	1
tendon of biceps brachii	1
ileal mucosa	1
left adrenal gland	1
left adrenal gland cortex	1
granulocyte	1
monocyte	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery
OPN1MW2	4		yes	primordial germ cell in gonad, colonic epithelium, ventricular zone
DNASE1L1	283	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, gluteal muscle
EMD	284	ubiquitous	marker	left ovary, left uterine tube, popliteal artery
HCFC1	274	ubiquitous	marker	tendon of biceps brachii, parotid gland, skeletal muscle tissue of rectus abdominis
ABCD1	201	ubiquitous	marker	ileal mucosa, left adrenal gland cortex, left adrenal gland
ARHGAP4	229	broad	marker	granulocyte, spleen, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNA	5,321
EMD	3,503
HCFC1	2,637
ABCD1	1,181
ARHGAP4	1,088
DNASE1L1	1,012
OPN1MW2	346

Structural data

PDB: 5 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNA	P21333	26
ABCD1	P33897	14
HCFC1	P51610	11
EMD	P50402	6
ARHGAP4	P98171	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNASE1L1	P49184	90.83
OPN1MW2	P0DN77	82.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 7 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCD1 causes ALD	1	951.7×	0.029	ABCD1
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1	317.2×	0.029	ABCD1
OAS antiviral response	1	211.5×	0.029	FLNA
Linoleic acid (LA) metabolism	1	190.3×	0.029	ABCD1
GP1b-IX-V activation signalling	1	158.6×	0.029	FLNA
Beta-oxidation of very long chain fatty acids	1	146.4×	0.029	ABCD1
Depolymerization of the Nuclear Lamina	1	126.9×	0.029	EMD
alpha-linolenic acid (ALA) metabolism	1	119.0×	0.029	ABCD1
Peroxisomal lipid metabolism	1	112.0×	0.029	ABCD1
Cell-extracellular matrix interactions	1	112.0×	0.029	FLNA
ABC transporters in lipid homeostasis	1	100.2×	0.029	ABCD1
Initiation of Nuclear Envelope (NE) Reformation	1	100.2×	0.029	EMD
RHO GTPases activate PAKs	1	90.6×	0.029	FLNA
Class I peroxisomal membrane protein import	1	86.5×	0.029	ABCD1
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	79.3×	0.029	EMD
Nuclear Envelope Breakdown	1	76.1×	0.029	EMD
ABC transporter disorders	1	73.2×	0.029	ABCD1
RAC1 GTPase cycle	2	20.4×	0.029	EMD, ARHGAP4
Formation of WDR5-containing histone-modifying complexes	1	44.3×	0.045	HCFC1
Transcriptional activation of mitochondrial biogenesis	1	34.0×	0.053	HCFC1
RHOD GTPase cycle	1	34.0×	0.053	EMD
Protein localization	1	31.7×	0.054	ABCD1
RHOG GTPase cycle	1	24.7×	0.065	EMD
Disorders of transmembrane transporters	1	23.2×	0.065	ABCD1
Fatty acid metabolism	1	21.9×	0.065	ABCD1
RAC2 GTPase cycle	1	21.1×	0.065	EMD
UCH proteinases	1	20.7×	0.065	HCFC1
ABC-family protein mediated transport	1	20.2×	0.065	ABCD1
RAC3 GTPase cycle	1	19.8×	0.065	EMD
Platelet degranulation	1	14.6×	0.084	FLNA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 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 membrane repolarization during atrial cardiac muscle cell action potential	1	2407.4×	0.013	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	2407.4×	0.013	FLNA
peroxisomal membrane transport	1	1203.7×	0.013	ABCD1
very long-chain fatty-acyl-CoA catabolic process	1	1203.7×	0.013	ABCD1
release from viral latency	1	802.5×	0.013	HCFC1
tubulin deacetylation	1	802.5×	0.013	FLNA
positive regulation of unsaturated fatty acid biosynthetic process	1	802.5×	0.013	ABCD1
formation of radial glial scaffolds	1	601.9×	0.013	FLNA
sterol homeostasis	1	601.9×	0.013	ABCD1
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	481.5×	0.013	FLNA
long-chain fatty acid import into peroxisome	1	481.5×	0.013	ABCD1
establishment of Sertoli cell barrier	1	481.5×	0.013	FLNA
absorption of visible light	1	401.2×	0.013	OPN1MW2
regulation of fatty acid beta-oxidation	1	401.2×	0.013	ABCD1
long-chain fatty acid catabolic process	1	401.2×	0.013	ABCD1
myelin maintenance	1	401.2×	0.013	ABCD1
regulation of mitochondrial depolarization	1	401.2×	0.013	ABCD1
protein localization to bicellular tight junction	1	401.2×	0.013	FLNA
negative regulation of transcription by RNA polymerase I	1	343.9×	0.013	FLNA
fatty acid elongation	1	343.9×	0.013	ABCD1
very long-chain fatty acid catabolic process	1	343.9×	0.013	ABCD1
nuclear membrane organization	1	343.9×	0.013	EMD
blood coagulation, intrinsic pathway	1	300.9×	0.014	FLNA
negative regulation of fibroblast migration	1	218.9×	0.017	ARHGAP4
positive regulation of fatty acid beta-oxidation	1	218.9×	0.017	ABCD1
fatty acid derivative biosynthetic process	1	218.9×	0.017	ABCD1
protein stabilization	2	19.1×	0.017	FLNA, HCFC1
positive regulation of platelet activation	1	185.2×	0.018	FLNA
regulation of cellular response to oxidative stress	1	185.2×	0.018	ABCD1
positive regulation of integrin-mediated signaling pathway	1	185.2×	0.018	FLNA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 3 of 7 evidence-associated genes (43%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLNA	1	2
HCFC1	1	2
OPN1MW2	0	0
DNASE1L1	0	0
EMD	0	0
ABCD1	0	0
ARHGAP4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	FLNA, HCFC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HCFC1	8	Binding:8
FLNA	7	Binding:7
EMD	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCD1	7.6.2.4	ABC-type fatty-acyl-CoA transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; 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	FLNA, HCFC1

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	2	FLNA, HCFC1
C	Druggable family + PDB, no drug	1	ABCD1
D	Druggable family + AlphaFold only, no drug	2	OPN1MW2, DNASE1L1
E	Difficult family or no structure, no drug	2	EMD, ARHGAP4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
OPN1MW2	0	—
DNASE1L1	0	—
EMD	1	—
ABCD1	0	—
ARHGAP4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.