intellectual disability, X-linked 1

Summary

intellectual disability, X-linked 1 (MONDO:0010656) is a disease caused by IQSEC2 (GenCC Definitive), with 5 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: IQSEC2 (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 1,109
• Phenotypes (HPO): 17
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000253	Progressive microcephaly	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0010864	Intellectual disability, severe	Frequent (30-79%)
HP:0012171	Stereotypical hand wringing	Frequent (30-79%)
HP:0012760	Reduced social responsiveness	Frequent (30-79%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000666	Horizontal nystagmus	Occasional (5-29%)
HP:0001344	Absent speech	Occasional (5-29%)
HP:0002487	Hyperkinetic movements	Occasional (5-29%)
HP:0030215	Inappropriate crying	Occasional (5-29%)
HP:0100716	Self-injurious behavior	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 1
Mondo ID	MONDO:0010656
MeSH	C564489, C567906
OMIM	309530
Orphanet	397933
DOID	DOID:0112038
NCIT	C133729
UMLS	C2931498
MedGen	444070
GARD	0022699
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 1, X-linked dominant · intellectual disability, X-linked 1 · IQSEC2 · IQSEC2-related disorder · IQSEC2-related epilepsy · IQSEC2-related intellectual disability · IQSEC2-related syndromic intellectual disability · mental retardation, X-linked 1 · mental retardation, X-linked 18 · mental retardation, X-linked 78 · mental retardation, X-linked type 1 · MRX · MRX1 · MRX78 · X-linked intellectual disability 1 · X-linked intellectual disability 1/78 · X-linked intellectual disability 78

Data availability: 1,109 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › non-syndromic X-linked intellectual disability › intellectual disability, X-linked 1

Related subtypes (51): intellectual disability, X-linked 23, intellectual disability, X-linked 20, intellectual disability, X-linked 14, intellectual disability, X-linked 50, intellectual disability, X-linked 21, intellectual disability, X-linked 58, intellectual disability, X-linked 72, intellectual disability, X-linked 53, intellectual disability, X-linked 73, intellectual disability, X-linked 42, intellectual disability, X-linked 63, intellectual disability, X-linked, with or without seizures, ARX-related, intellectual disability, X-linked 2, intellectual disability, X-linked 81, intellectual disability, X-linked 46, intellectual disability, X-linked 77, intellectual disability, X-linked 45, intellectual disability, X-linked 84, intellectual disability, X-linked 82, intellectual disability, X-linked 30, intellectual disability, X-linked 91, intellectual disability, X-linked 93, chromosome Xp11.22 duplication syndrome, intellectual disability, X-linked 95, intellectual disability, X-linked 96, intellectual disability, X-linked 97, intellectual disability, X-linked 19, intellectual disability, X-linked 89, intellectual disability, X-linked 41, intellectual disability, X-linked 90, intellectual disability, X-linked 92, intellectual disability, X-linked 88, intellectual disability, X-linked 99, intellectual disability, X-linked 100, intellectual disability, X-linked 101, intellectual disability, X-linked 102, intellectual disability, X-linked 61, intellectual disability, X-linked 103, intellectual disability, X-linked 104, intellectual disability, X-linked 105, methylmalonic acidemia with homocystinuria, type cblX, FRAXE intellectual disability, intellectual disability, X-linked 9, intellectual developmental disorder, X-linked 108, intellectual disability, X-linked 106, intellectual disability, X-linked 107, intellectual developmental disorder, X-linked 110, intellectual developmental disorder, X-linked 111, intellectual developmental disorder, X-linked 112, intellectual developmental disorder, X-linked 113, intellectual developmental disorder, X-linked 114

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:

225 likely benign, 205 uncertain significance, 57 pathogenic, 45 benign, 41 conflicting classifications of pathogenicity, 16 likely pathogenic, 10 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069101	NM_001111125.3(IQSEC2):c.3611_3791del (p.Phe1204fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1070778	NM_001111125.3(IQSEC2):c.3433C>T (p.Arg1145Ter)	IQSEC2	Pathogenic	criteria provided, multiple submitters, no conflicts
1071797	NM_001111125.3(IQSEC2):c.1925del (p.Pro642fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1072485	NM_001111125.3(IQSEC2):c.2336_2337del (p.Gly779fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1074866	NM_001111125.3(IQSEC2):c.3237del (p.Ile1080fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1075324	NM_001111125.3(IQSEC2):c.3387C>G (p.Tyr1129Ter)	IQSEC2	Pathogenic	criteria provided, single submitter
1076348	NC_000023.10:g.(?53270946)(53271111_?)del	IQSEC2	Pathogenic	criteria provided, single submitter
1076522	NM_001111125.3(IQSEC2):c.4402_4418dup (p.Ser1474fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1076577	NM_001111125.3(IQSEC2):c.3106C>T (p.Gln1036Ter)	IQSEC2	Pathogenic	criteria provided, single submitter
10863	NM_001111125.3(IQSEC2):c.2402A>C (p.Gln801Pro)	IQSEC2	Pathogenic	no assertion criteria provided
10864	NM_001111125.3(IQSEC2):c.2273G>A (p.Arg758Gln)	IQSEC2	Pathogenic	no assertion criteria provided
1176938	NM_001111125.3(IQSEC2):c.828del (p.Ser277fs)	IQSEC2	Pathogenic	criteria provided, multiple submitters, no conflicts
126417	NM_001111125.3(IQSEC2):c.2563C>T (p.Arg855Ter)	IQSEC2	Pathogenic	criteria provided, multiple submitters, no conflicts
1323121	NM_001111125.3(IQSEC2):c.2225G>A (p.Trp742Ter)	IQSEC2	Pathogenic	criteria provided, single submitter
1338309	NM_001111125.3(IQSEC2):c.3163C>T (p.Arg1055Ter)	IQSEC2	Pathogenic	criteria provided, multiple submitters, no conflicts
1361147	NM_001111125.3(IQSEC2):c.705delA (p.Lys236fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1376143	NM_001111125.3(IQSEC2):c.627del (p.Ser210fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1406772	NM_001111125.3(IQSEC2):c.2380G>T (p.Glu794Ter)	IQSEC2	Pathogenic	criteria provided, single submitter
1408417	NM_001111125.3(IQSEC2):c.4334del (p.Pro1445fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1418285	NM_001111125.3(IQSEC2):c.1296T>G (p.Tyr432Ter)	IQSEC2	Pathogenic	criteria provided, single submitter
1452197	NM_001111125.3(IQSEC2):c.2305G>T (p.Glu769Ter)	IQSEC2	Pathogenic	criteria provided, single submitter
1454379	NM_001111125.3(IQSEC2):c.4410dup (p.Asn1471fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1457021	NM_001111125.3(IQSEC2):c.4214dup (p.Gly1407fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1457780	NC_000023.10:g.(?53279441)(53280376_?)del	IQSEC2	Pathogenic	criteria provided, single submitter
1685889	NM_001111125.3(IQSEC2):c.3875dup (p.Pro1293fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1685890	NM_001111125.3(IQSEC2):c.3452-1G>A	IQSEC2	Pathogenic	criteria provided, single submitter
1685891	NM_001111125.3(IQSEC2):c.2840dup (p.His947fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1699072	NM_001111125.3(IQSEC2):c.1483C>T (p.Gln495Ter)	IQSEC2	Pathogenic	criteria provided, single submitter
1802601	NM_001111125.3(IQSEC2):c.3613del (p.Leu1205fs)	IQSEC2	Pathogenic	criteria provided, single submitter
1803041	NM_001111125.3(IQSEC2):c.3016-1G>T	IQSEC2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 11 · 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
IQSEC2	Definitive	X-linked	intellectual disability, X-linked 1	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IQSEC2	Orphanet:217377	Microduplication Xp11.22p11.23 syndrome
IQSEC2	Orphanet:397933	Severe intellectual disability-progressive postnatal microcephaly-midline stereotypic hand movements syndrome
IQSEC2	Orphanet:819	Smith-Magenis syndrome
SMC1A	Orphanet:199	Cornelia de Lange syndrome
SMC1A	Orphanet:220386	Semilobar holoprosencephaly
SMC1A	Orphanet:3095	Atypical Rett syndrome
SMC1A	Orphanet:708203	Intellectual disability-small hands and feet-drug-resistant epilepsy syndrome
TSR2	Orphanet:124	Diamond-Blackfan anemia
HSD17B10	Orphanet:391428	HSD10 disease, infantile type
HSD17B10	Orphanet:391457	HSD10 disease, neonatal type
HSD17B10	Orphanet:85295	HSD10 disease, atypical type

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IQSEC2	HGNC:29059	ENSG00000124313	Q5JU85	IQ motif and SEC7 domain-containing protein 2	gencc,clinvar
SMC1A	HGNC:11111	ENSG00000072501	Q14683	Structural maintenance of chromosomes protein 1A	clinvar
TSR2	HGNC:25455	ENSG00000158526	Q969E8	Pre-rRNA-processing protein TSR2 homolog	clinvar
RIBC1	HGNC:26537	ENSG00000158423	Q8N443	RIB43A-like with coiled-coils protein 1	clinvar
HSD17B10	HGNC:4800	ENSG00000072506	Q99714	3-hydroxyacyl-CoA dehydrogenase type-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IQSEC2	IQ motif and SEC7 domain-containing protein 2	Is a guanine nucleotide exchange factor for the ARF GTP-binding proteins.
SMC1A	Structural maintenance of chromosomes protein 1A	Involved in chromosome cohesion during cell cycle and in DNA repair.
TSR2	Pre-rRNA-processing protein TSR2 homolog	May be involved in 20S pre-rRNA processing.
HSD17B10	3-hydroxyacyl-CoA dehydrogenase type-2	Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.2

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
Scaffold/PPI	1	3.5×	0.530
Enzyme (other)	1	2.4×	0.530
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IQSEC2	Scaffold/PPI	no		Sec7_dom, PH_domain, PH-like_dom_sf
SMC1A	Other/Unknown	no		RecF/RecN/SMC_N, SMC_hinge, SMC
TSR2	Other/Unknown	no		Pre-rRNA_process_TSR2
RIBC1	Other/Unknown	no		RIB43A
HSD17B10	Enzyme (other)	yes	1.1.1.135	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

4 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
embryo	1
sural nerve	1
trabecular bone tissue	1
globus pallidus	1
medial globus pallidus	1
tendon of biceps brachii	1
bronchial epithelial cell	1
bronchus	1
right uterine tube	1
liver	1
right adrenal gland	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IQSEC2	236	ubiquitous	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
SMC1A	289	ubiquitous	marker	sural nerve, trabecular bone tissue, embryo
TSR2	289	ubiquitous	marker	tendon of biceps brachii, medial globus pallidus, globus pallidus
RIBC1	165	broad	marker	right uterine tube, bronchial epithelial cell, bronchus
HSD17B10	155	ubiquitous	marker	right lobe of liver, liver, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMC1A	5,246
HSD17B10	2,961
RIBC1	2,045
TSR2	1,969
IQSEC2	1,296

Intra-cohort edges

A	B	Sources
HSD17B10	RIBC1	string_interaction
IQSEC2	SMC1A	string_interaction
RIBC1	SMC1A	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMC1A	Q14683	18
HSD17B10	Q99714	15
IQSEC2	Q5JU85	2
RIBC1	Q8N443	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSR2	Q969E8	74.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 5 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
tRNA processing in the mitochondrion	1	1142.0×	0.009	HSD17B10
Mitotic Telophase/Cytokinesis	1	713.8×	0.009	SMC1A
rRNA processing in the mitochondrion	1	634.4×	0.009	HSD17B10
Cohesin Loading onto Chromatin	1	571.0×	0.009	SMC1A
Establishment of Sister Chromatid Cohesion	1	519.1×	0.009	SMC1A
tRNA modification in the mitochondrion	1	519.1×	0.009	HSD17B10
Branched-chain amino acid catabolism	1	237.9×	0.017	HSD17B10
Meiosis	1	142.8×	0.025	SMC1A
Reproduction	1	95.2×	0.029	SMC1A
S Phase	1	90.6×	0.029	SMC1A
SUMO E3 ligases SUMOylate target proteins	1	89.2×	0.029	SMC1A
SUMOylation	1	81.6×	0.029	SMC1A
SUMOylation of DNA damage response and repair proteins	1	73.2×	0.029	SMC1A
Meiotic synapsis	1	70.5×	0.029	SMC1A
ESR-mediated signaling	1	64.2×	0.030	SMC1A
Mitochondrial protein degradation	1	57.1×	0.031	HSD17B10
Signaling by Nuclear Receptors	1	51.0×	0.031	SMC1A
Mitotic Metaphase and Anaphase	1	48.4×	0.031	SMC1A
Mitotic Anaphase	1	48.4×	0.031	SMC1A
Resolution of Sister Chromatid Cohesion	1	43.3×	0.033	SMC1A
Estrogen-dependent gene expression	1	37.8×	0.036	SMC1A
Mitotic Prometaphase	1	34.6×	0.038	SMC1A
M Phase	1	33.0×	0.038	SMC1A
Separation of Sister Chromatids	1	30.4×	0.039	SMC1A
Cell Cycle, Mitotic	1	24.1×	0.048	SMC1A
Cell Cycle	1	18.0×	0.061	SMC1A
Post-translational protein modification	1	9.6×	0.109	SMC1A
Metabolism of proteins	1	6.2×	0.161	SMC1A
Signal Transduction	1	5.1×	0.187	SMC1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
brexanolone metabolic process	1	3370.4×	0.007	HSD17B10
response to DNA damage checkpoint signaling	1	1685.2×	0.007	SMC1A
mitochondrial tRNA methylation	1	1123.5×	0.007	HSD17B10
mitochondrial tRNA 5’-end processing	1	1123.5×	0.007	HSD17B10
establishment of meiotic sister chromatid cohesion	1	842.6×	0.007	SMC1A
mitochondrial tRNA 3’-end processing	1	842.6×	0.007	HSD17B10
C21-steroid hormone metabolic process	1	674.1×	0.007	HSD17B10
L-isoleucine catabolic process	1	561.7×	0.008	HSD17B10
establishment of mitotic sister chromatid cohesion	1	481.5×	0.008	SMC1A
positive regulation of long-term synaptic depression	1	374.5×	0.009	IQSEC2
response to radiation	1	240.7×	0.013	SMC1A
mitotic sister chromatid cohesion	1	224.7×	0.013	SMC1A
androgen metabolic process	1	177.4×	0.013	HSD17B10
regulation of ARF protein signal transduction	1	177.4×	0.013	IQSEC2
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	177.4×	0.013	IQSEC2
sister chromatid cohesion	1	153.2×	0.014	SMC1A
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	134.8×	0.014	TSR2
bile acid biosynthetic process	1	124.8×	0.014	HSD17B10
estrogen metabolic process	1	124.8×	0.014	HSD17B10
positive regulation of synaptic transmission, glutamatergic	1	124.8×	0.014	IQSEC2
mitotic sister chromatid segregation	1	96.3×	0.017	SMC1A
fatty acid beta-oxidation	1	74.9×	0.021	HSD17B10
mitotic spindle assembly	1	68.8×	0.022	SMC1A
somatic stem cell population maintenance	1	49.6×	0.027	SMC1A
meiotic cell cycle	1	48.9×	0.027	SMC1A
positive regulation of synapse assembly	1	48.9×	0.027	IQSEC2
protein homotetramerization	1	47.5×	0.027	HSD17B10
fatty acid metabolic process	1	38.7×	0.032	HSD17B10
modulation of chemical synaptic transmission	1	36.6×	0.033	IQSEC2
mitochondrion organization	1	30.4×	0.038	HSD17B10

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 5 evidence-associated genes (40%) 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
SMC1A	SELUMETINIB
HSD17B10	LEVODOPA

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HSD17B10	249	4
SMC1A	2	4
IQSEC2	0	0
TSR2	0	0
RIBC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SELUMETINIB	4	SMC1A
LEVODOPA	4	HSD17B10
PHENYLBUTAZONE	4	HSD17B10
CANDESARTAN CILEXETIL	4	HSD17B10
TELMISARTAN	4	HSD17B10
DIENESTROL	4	HSD17B10
CHOLECALCIFEROL	4	HSD17B10
BUMETANIDE	4	HSD17B10
SALMETEROL XINAFOATE	4	HSD17B10
SULFAPHENAZOLE	4	HSD17B10
RALOXIFENE HYDROCHLORIDE	4	HSD17B10
DICYCLOMINE	4	HSD17B10
CISPLATIN	4	HSD17B10
TETRABENAZINE	4	HSD17B10
DECAMETHONIUM	4	HSD17B10
LABETALOL HYDROCHLORIDE	4	HSD17B10
DIMENHYDRINATE	4	HSD17B10
HYDROXYZINE PAMOATE	4	HSD17B10
MALATHION	4	HSD17B10
PYRITHIONE ZINC	4	HSD17B10
AVOBENZONE	4	HSD17B10
CEFOXITIN SODIUM	4	HSD17B10
OXYMETHOLONE	4	HSD17B10
FEXOFENADINE HYDROCHLORIDE	4	HSD17B10
GEMIFLOXACIN MESYLATE	4	HSD17B10
AMPICILLIN SODIUM	4	HSD17B10
CHLOROTRIANISENE	4	HSD17B10
TRAZODONE HYDROCHLORIDE	4	HSD17B10
ETHOPROPAZINE HYDROCHLORIDE	4	HSD17B10
PHENAZOPYRIDINE HYDROCHLORIDE	4	HSD17B10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HSD17B10	41	Binding:39, Functional:2
SMC1A	10	Binding:10

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HSD17B10	1.1.1.135, 1.1.1.178, 1.1.1.35, 1.1.1.62	GDP-6-deoxy-D-talose 4-dehydrogenase, 3-hydroxy-2-methylbutyryl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, 17beta-estradiol 17-dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
SELUMETINIB	4	SMC1A
LEVODOPA	4	HSD17B10
PHENYLBUTAZONE	4	HSD17B10
CANDESARTAN CILEXETIL	4	HSD17B10
TELMISARTAN	4	HSD17B10
DIENESTROL	4	HSD17B10
CHOLECALCIFEROL	4	HSD17B10
BUMETANIDE	4	HSD17B10
SALMETEROL XINAFOATE	4	HSD17B10
SULFAPHENAZOLE	4	HSD17B10
RALOXIFENE HYDROCHLORIDE	4	HSD17B10
DICYCLOMINE	4	HSD17B10
CISPLATIN	4	HSD17B10
TETRABENAZINE	4	HSD17B10
DECAMETHONIUM	4	HSD17B10
LABETALOL HYDROCHLORIDE	4	HSD17B10
DIMENHYDRINATE	4	HSD17B10
HYDROXYZINE PAMOATE	4	HSD17B10
MALATHION	4	HSD17B10
PYRITHIONE ZINC	4	HSD17B10
AVOBENZONE	4	HSD17B10
CEFOXITIN SODIUM	4	HSD17B10
OXYMETHOLONE	4	HSD17B10
FEXOFENADINE HYDROCHLORIDE	4	HSD17B10
GEMIFLOXACIN MESYLATE	4	HSD17B10
AMPICILLIN SODIUM	4	HSD17B10
CHLOROTRIANISENE	4	HSD17B10
TRAZODONE HYDROCHLORIDE	4	HSD17B10
ETHOPROPAZINE HYDROCHLORIDE	4	HSD17B10
PHENAZOPYRIDINE HYDROCHLORIDE	4	HSD17B10

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SMC1A, HSD17B10
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	3	IQSEC2, TSR2, RIBC1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IQSEC2	0	SMC1A
RIBC1	0	HSD17B10, SMC1A
TSR2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight