Autosomal recessive congenital ichthyosis

Summary

Autosomal recessive congenital ichthyosis (MONDO:0017265) is a disease (an umbrella term covering 13 Mondo subtypes) caused by ABCA12 (GenCC Strong), with 11 cohort genes and 2 clinical trials. Top therapeutic interventions include secukinumab.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: ABCA12 (GenCC Strong)
• Umbrella term: 13 Mondo subtypes
• Cohort genes: 11
• ClinVar variants: 16
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.5	Europe	Validated
Annual incidence	1-9 / 100 000	1.1	Norway	Validated
Annual incidence	1-9 / 1 000 000	0.5	United States	Not yet validated
Point prevalence	1-9 / 1 000 000	0.77	Spain	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive congenital ichthyosis
Mondo ID	MONDO:0017265
OMIM	242300
Orphanet	281097
DOID	DOID:0060655
ICD-11	430849255
UMLS	C1274215
MedGen	697564
GARD	0021106
Is cancer (heuristic)	no

Also known as: ARCI · autosomal recessive inherited ichthyosis · ichthyosis, congenital, autosomal recessive · inherited ichthyosis, autosomal recessive

Data availability: 16 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 13 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › ichthyosis › inherited ichthyosis › autosomal recessive congenital ichthyosis

Related subtypes (12): congenital cataract-ichthyosis syndrome, Netherton syndrome, ichthyosis-oral and digital anomalies syndrome, recessive X-linked ichthyosis, neonatal ichthyosis-sclerosing cholangitis syndrome, keratinopathic ichthyosis, peeling skin syndrome, ichthyosis vulgaris, ichthyosis linearis circumflexa, IFAP syndrome, ichthyosis hystrix, ichthyosis with erythrokeratoderma

Subtypes (13): autosomal recessive congenital ichthyosis 1, autosomal recessive congenital ichthyosis 4A, autosomal recessive congenital ichthyosis 11, autosomal recessive congenital ichthyosis 5, autosomal recessive congenital ichthyosis 8, ichthyosis, congenital, autosomal recessive 12, bathing suit ichthyosis, self-healing collodion baby, acral self-healing collodion baby, exfoliative ichthyosis, congenital non-bullous ichthyosiform erythroderma, ichthyosis, congenital, autosomal recessive 14, ichthyosis, congenital, autosomal recessive 13

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

16 retrieved; paginated sample, class counts are floors:

4 pathogenic, 4 conflicting classifications of pathogenicity, 3 uncertain significance, 3 pathogenic/likely pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1252008	NC_000002.11:g.(215928788_?)del		Pathogenic	no assertion criteria provided
279677	NM_021628.3(ALOXE3):c.1889C>T (p.Pro630Leu)	ALOXE3	Pathogenic	criteria provided, multiple submitters, no conflicts
1731	NM_001099287.2(NIPAL4):c.341C>A (p.Ala114Asp)	NIPAL4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372383	NM_001099287.2(NIPAL4):c.502G>A (p.Gly168Arg)	NIPAL4	Pathogenic	criteria provided, multiple submitters, no conflicts
617846	NM_001374623.1(PNPLA1):c.387C>A (p.Asp129Glu)	PNPLA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5742	NM_005094.4(SLC27A4):c.504C>A (p.Cys168Ter)	SLC27A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279911	NM_000359.3(TGM1):c.877-2A>G	TGM1	Pathogenic	criteria provided, multiple submitters, no conflicts
4074948	NM_001013838.3(CARMIL2):c.611+5G>A	CARMIL2	Likely pathogenic	criteria provided, single submitter
4075176	NM_001099287.2(NIPAL4):c.586+1G>T	NIPAL4	Likely pathogenic	criteria provided, single submitter
995715	NM_001139.3(ALOX12B):c.1405C>T (p.Arg469Trp)	ALOX12B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4075000	NM_021628.3(ALOXE3):c.981C>A (p.Asp327Glu)	ALOXE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16320	NM_002016.2(FLG):c.2282_2285del (p.Ser761fs)	CCDST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870787	NM_002016.2(FLG):c.10255C>T (p.Arg3419Ter)	CCDST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4074999	NM_001139.3(ALOX12B):c.1153G>T (p.Val385Leu)	ALOX12B	Uncertain significance	criteria provided, single submitter
1486418	NM_021813.4(BACH2):c.100G>A (p.Asp34Asn)	BACH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
4074769	NM_000243.3(MEFV):c.565G>A (p.Gly189Ser)	MEFV	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 24 · 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
ABCA12	Definitive	Autosomal recessive	autosomal recessive congenital ichthyosis 4B	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCA12	Orphanet:313	Lamellar ichthyosis
ABCA12	Orphanet:457	Harlequin ichthyosis
ABCA12	Orphanet:79394	Congenital ichthyosiform erythroderma
SLC27A4	Orphanet:88621	Ichthyosis-prematurity syndrome
TGM1	Orphanet:100976	Bathing suit ichthyosis
TGM1	Orphanet:281122	Self-improving collodion baby
TGM1	Orphanet:281127	Acral self-healing collodion baby
TGM1	Orphanet:313	Lamellar ichthyosis
TGM1	Orphanet:79394	Congenital ichthyosiform erythroderma
ALOXE3	Orphanet:281122	Self-improving collodion baby
ALOXE3	Orphanet:313	Lamellar ichthyosis
ALOXE3	Orphanet:79394	Congenital ichthyosiform erythroderma
BACH2	Orphanet:714472	Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
PNPLA1	Orphanet:79394	Congenital ichthyosiform erythroderma
CARMIL2	Orphanet:542301	EBV-induced lymphoproliferative disease due to CARMIL2 deficiency
NIPAL4	Orphanet:313	Lamellar ichthyosis
NIPAL4	Orphanet:79394	Congenital ichthyosiform erythroderma
ALOX12B	Orphanet:281122	Self-improving collodion baby
ALOX12B	Orphanet:313	Lamellar ichthyosis
ALOX12B	Orphanet:79394	Congenital ichthyosiform erythroderma
MEFV	Orphanet:117	Behçet disease
MEFV	Orphanet:3243	Sweet syndrome
MEFV	Orphanet:329967	Intermittent hydrarthrosis
MEFV	Orphanet:342	Familial Mediterranean fever

Cohort genes → proteins

11 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	11

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABCA12	HGNC:14637	ENSG00000144452	Q86UK0	Glucosylceramide transporter ABCA12	gencc
SLC27A4	HGNC:10998	ENSG00000167114	Q6P1M0	Long-chain fatty acid transport protein 4	clinvar
TGM1	HGNC:11777	ENSG00000092295	P22735	Protein-glutamine gamma-glutamyltransferase K	clinvar
ALOXE3	HGNC:13743	ENSG00000179148	Q9BYJ1	Hydroperoxide isomerase ALOXE3	clinvar
BACH2	HGNC:14078	ENSG00000112182	Q9BYV9	Transcription regulator protein BACH2	clinvar
PNPLA1	HGNC:21246	ENSG00000180316	Q8N8W4	Omega-hydroxyceramide transacylase	clinvar
CARMIL2	HGNC:27089	ENSG00000159753	Q6F5E8	Capping protein, Arp2/3 and myosin-I linker protein 2	clinvar
NIPAL4	HGNC:28018	ENSG00000172548	Q0D2K0	Magnesium transporter NIPA4	clinvar
ALOX12B	HGNC:430	ENSG00000179477	O75342	Arachidonate 12-lipoxygenase, 12R-type	clinvar
CCDST	HGNC:55988	ENSG00000236427		cervical cancer associated DHX9 suppressive transcript	clinvar
MEFV	HGNC:6998	ENSG00000103313	O15553	Pyrin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCA12	Glucosylceramide transporter ABCA12	Transports lipids such as glucosylceramides from the outer to the inner leaflet of lamellar granules (LGs) membrane, whereby the lipids are finally transported to the keratinocyte periphery via the trans-Golgi network and LGs and released…
SLC27A4	Long-chain fatty acid transport protein 4	Mediates the levels of long-chain fatty acids (LCFA) in the cell by facilitating their transport across cell membranes.
TGM1	Protein-glutamine gamma-glutamyltransferase K	Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.
ALOXE3	Hydroperoxide isomerase ALOXE3	Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced lipoxygenases activity.
BACH2	Transcription regulator protein BACH2	Transcriptional regulator that acts as a repressor or activator.
PNPLA1	Omega-hydroxyceramide transacylase	Omega-hydroxyceramide transacylase involved in the synthesis of omega-O-acylceramides (esterified omega-hydroxyacyl-sphingosine; EOS), which are extremely hydrophobic lipids involved in skin barrier formation.
CARMIL2	Capping protein, Arp2/3 and myosin-I linker protein 2	Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments.
NIPAL4	Magnesium transporter NIPA4	Acts as a Mg(2+) transporter.
ALOX12B	Arachidonate 12-lipoxygenase, 12R-type	Catalyzes the regio and stereo-specific incorporation of a single molecule of dioxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species.
MEFV	Pyrin	Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma.

Protein-family classification

Druggable: 6 · Difficult: 2 · Unknown: 3 · Druggable fraction: 0.55

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)	4	4.4×	0.049
Transporter	1	7.1×	0.332
Antibody/Immunoglobulin	1	2.6×	0.490
Transcription factor	2	1.5×	0.490
Other/Unknown	3	0.5×	0.987

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCA12	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
SLC27A4	Enzyme (other)	yes	6.2.1.3	AMP-dep_synth/lig_dom, AMP-binding_CS, Lipocalin_CS
TGM1	Antibody/Immunoglobulin	yes	2.3.2.13	Transglutaminase_N, Transglutaminase-like, Transglutaminase_C
ALOXE3	Enzyme (other)	yes	4.2.1.152	LipOase, PLAT/LH2_dom, LipOase_mml
BACH2	Transcription factor	no		BTB/POZ_dom, bZIP_Maf, bZIP
PNPLA1	Enzyme (other)	yes	2.3.1.296	PNPLA_dom, Acyl_Trfase/lysoPLipase, PLPL
CARMIL2	Other/Unknown	no		Leu-rich_rpt, PH-like_dom_sf, CARMIL_C
NIPAL4	Other/Unknown	no		Mg_trans_NIPA, EmrE-like
ALOX12B	Enzyme (other)	yes	1.13.11.31	LipOase, PLAT/LH2_dom, LipOase_mml
CCDST	Other/Unknown	no
MEFV	Transcription factor	no		Znf_B-box, B30.2/SPRY, SPRY_dom

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)	0
moderate (6-20)	0
broad (>20)	11
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of leg	5
skin of abdomen	4
lower esophagus mucosa	3
zone of skin	3
upper arm skin	2
penis	1
upper leg skin	1
jejunal mucosa	1
mucosa of transverse colon	1
esophagus mucosa	1
cortical plate	1
epithelium of nasopharynx	1
sural nerve	1
anterior cingulate cortex	1
right frontal lobe	1
right hemisphere of cerebellum	1
male germ line stem cell (sensu Vertebrata) in testis	1
quadriceps femoris	1
buccal mucosa cell	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCA12	95	broad	marker	penis, upper leg skin, upper arm skin
SLC27A4	219	ubiquitous	yes	mucosa of transverse colon, lower esophagus mucosa, jejunal mucosa
TGM1	135	broad	marker	lower esophagus mucosa, esophagus mucosa, skin of leg
ALOXE3	141	tissue_specific	yes	skin of leg, skin of abdomen, zone of skin
BACH2	237	ubiquitous	marker	cortical plate, sural nerve, epithelium of nasopharynx
PNPLA1	104	tissue_specific	marker	skin of abdomen, skin of leg, zone of skin
CARMIL2	183	ubiquitous	yes	right frontal lobe, anterior cingulate cortex, right hemisphere of cerebellum
NIPAL4	165	broad	marker	upper arm skin, skin of abdomen, skin of leg
ALOX12B	168	broad	yes	skin of leg, skin of abdomen, zone of skin
CCDST	111	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, lower esophagus mucosa, quadriceps femoris
MEFV	153	broad	marker	buccal mucosa cell, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 19.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEFV	2,217
SLC27A4	2,199
TGM1	1,978
BACH2	1,917
ABCA12	1,137
ALOXE3	1,129
ALOX12B	1,126
CARMIL2	645
PNPLA1	584
NIPAL4	540

Intra-cohort edges

A	B	Sources
ABCA12	ALOX12B	string_interaction
ABCA12	ALOXE3	string_interaction
ABCA12	NIPAL4	string_interaction
ABCA12	PNPLA1	string_interaction
ABCA12	TGM1	string_interaction
ALOX12B	ALOXE3	intact
ALOX12B	NIPAL4	string_interaction
ALOX12B	PNPLA1	string_interaction
ALOX12B	SLC27A4	string_interaction
ALOX12B	TGM1	string_interaction
ALOXE3	NIPAL4	string_interaction
ALOXE3	PNPLA1	string_interaction
ALOXE3	SLC27A4	string_interaction
ALOXE3	TGM1	string_interaction
NIPAL4	PNPLA1	string_interaction
NIPAL4	SLC27A4	intact, string_interaction
NIPAL4	TGM1	string_interaction
PNPLA1	SLC27A4	string_interaction
PNPLA1	TGM1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 6 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEFV	O15553	11
BACH2	Q9BYV9	2
TGM1	P22735	1
ALOXE3	Q9BYJ1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALOX12B	O75342	92.07
SLC27A4	Q6P1M0	90.72
NIPAL4	Q0D2K0	78.91
ABCA12	Q86UK0	68.32
PNPLA1	Q8N8W4	64.54
CARMIL2	Q6F5E8	61.50

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 11 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of 12-eicosatetraenoic acid derivatives	2	466.1×	2e-04	ALOXE3, ALOX12B
Arachidonate metabolism	2	163.1×	9e-04	ALOXE3, ALOX12B
Defective SLC27A4 causes ichthyosis prematurity syndrome (IPS)	1	1631.4×	0.005	SLC27A4
Defective ABCA12 causes ARCI4B	1	1631.4×	0.005	ABCA12
Disorders of transmembrane transporters	2	39.8×	0.006	SLC27A4, ABCA12
Fatty acid metabolism	2	37.5×	0.006	ALOXE3, ALOX12B
Transport of fatty acids	1	203.9×	0.021	SLC27A4
Inflammasomes	1	163.1×	0.021	MEFV
Cell recruitment (pro-inflammatory response)	1	163.1×	0.021	MEFV
The NLRP3 inflammasome	1	96.0×	0.032	MEFV
ABC transporters in lipid homeostasis	1	85.9×	0.032	ABCA12
Disease	3	5.6×	0.032	SLC27A4, ABCA12, MEFV
Miscellaneous transport and binding events	1	62.8×	0.034	NIPAL4
ABC transporter disorders	1	62.8×	0.034	ABCA12
Purinergic signaling in leishmaniasis infection	1	60.4×	0.034	MEFV
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	51.0×	0.035	MEFV
Metabolism of lipids	2	9.0×	0.035	ALOXE3, ALOX12B
Transport of vitamins, nucleosides, and related molecules	1	38.8×	0.044	SLC27A4
Transport of small molecules	2	7.2×	0.047	SLC27A4, ABCA12
SLC transporter disorders	1	29.1×	0.052	SLC27A4
Leishmania infection	1	23.3×	0.059	MEFV
Parasitic Infection Pathways	1	23.3×	0.059	MEFV
ABC-family protein mediated transport	1	17.4×	0.076	ABCA12
Formation of the cornified envelope	1	12.6×	0.100	TGM1
SLC-mediated transmembrane transport	1	8.4×	0.137	SLC27A4
Keratinization	1	8.0×	0.137	TGM1
Metabolism	2	3.3×	0.137	ALOXE3, ALOX12B
Innate Immune System	1	3.6×	0.267	MEFV
Infectious disease	1	3.5×	0.267	MEFV
Developmental Biology	1	2.1×	0.408	TGM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
establishment of skin barrier	3	136.6×	7e-05	ALOXE3, ABCA12, ALOX12B
ceramide biosynthetic process	3	126.4×	7e-05	ALOXE3, PNPLA1, ALOX12B
lipid oxidation	2	421.3×	2e-04	ALOXE3, ALOX12B
hepoxilin biosynthetic process	2	421.3×	2e-04	ALOXE3, ALOX12B
lipoxygenase pathway	2	306.4×	3e-04	ALOXE3, ALOX12B
sphingolipid metabolic process	2	198.3×	7e-04	ALOXE3, ALOX12B
linoleic acid metabolic process	2	140.4×	0.001	ALOXE3, ALOX12B
arachidonate metabolic process	2	96.3×	0.002	ALOXE3, ALOX12B
lipid homeostasis	2	67.4×	0.004	ABCA12, PNPLA1
positive regulation of intracellular lipid transport	1	1685.2×	0.004	ABCA12
establishment or maintenance of monopolar cell polarity	1	1685.2×	0.004	CARMIL2
primary adaptive immune response involving T cells and B cells	1	1685.2×	0.004	BACH2
omega-hydroxyceramide biosynthetic process	1	1685.2×	0.004	PNPLA1
medium-chain fatty acid transport	1	842.6×	0.006	SLC27A4
corneocyte desquamation	1	842.6×	0.006	ABCA12
positive regulation of lamellipodium organization	1	842.6×	0.006	CARMIL2
pyroptosome complex assembly	1	842.6×	0.006	MEFV
cell envelope organization	1	561.7×	0.009	TGM1
negative regulation of macrophage inflammatory protein 1 alpha production	1	561.7×	0.009	MEFV
negative regulation of barbed-end actin filament capping	1	421.3×	0.011	CARMIL2
protein lipidation	1	337.0×	0.012	ALOX12B
positive regulation of mucus secretion	1	337.0×	0.012	ALOX12B
lipid transport across blood-brain barrier	1	337.0×	0.012	SLC27A4
glucose import in response to insulin stimulus	1	280.9×	0.014	SLC27A4
very long-chain fatty acid catabolic process	1	240.7×	0.015	SLC27A4
import into nucleus	1	240.7×	0.015	BACH2
regulation of interleukin-1 beta production	1	210.7×	0.016	MEFV
actin filament network formation	1	187.2×	0.018	CARMIL2
secretion by cell	1	168.5×	0.018	ABCA12
long-chain fatty acid import into cell	1	168.5×	0.018	SLC27A4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 11

Druggability breadth: 4 of 11 evidence-associated genes (36%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCA12	0	0
SLC27A4	0	0
TGM1	0	0
ALOXE3	0	0
BACH2	0	0
PNPLA1	0	0
CARMIL2	0	0
NIPAL4	0	0
ALOX12B	0	0
CCDST	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
TGM1	11	Binding:11
BACH2	3	Binding:3
SLC27A4	1	Binding:1
MEFV	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SLC27A4	6.2.1.3	long-chain-fatty-acid-CoA ligase
TGM1	2.3.2.13	protein-glutamine gamma-glutamyltransferase
ALOXE3	4.2.1.152	hydroperoxy icosatetraenoate dehydratase
PNPLA1	2.3.1.296	omega-hydroxyceramide transacylase
ALOX12B	1.13.11.31	arachidonate 12-lipoxygenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; 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	2	TGM1, ALOXE3
D	Druggable family + AlphaFold only, no drug	4	ABCA12, SLC27A4, PNPLA1, ALOX12B
E	Difficult family or no structure, no drug	5	BACH2, CARMIL2, NIPAL4, CCDST, MEFV

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ABCA12	0	—
SLC27A4	1	—
TGM1	11	—
ALOXE3	0	—
BACH2	3	—
PNPLA1	0	—
CARMIL2	0	—
NIPAL4	0	—
ALOX12B	0	—
CCDST	0	—
MEFV	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03041038	PHASE2	COMPLETED	The Efficacy and Safety of Secukinumab in Patients With Ichthyoses
NCT05312073	Not specified	COMPLETED	Study of in Vivo and in Vitro Transcriptomic and Proteomic Signatures in Unhereditary Ichtyosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SECUKINUMAB	4	1