severe combined immunodeficiency due to CARMIL2 deficiency

Summary

severe combined immunodeficiency due to CARMIL2 deficiency (MONDO:0029134) is a disease caused by CARMIL2 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CARMIL2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 46

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		21	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	severe combined immunodeficiency due to CARMIL2 deficiency
Mondo ID	MONDO:0029134
OMIM	618131
Orphanet	542301
DOID	DOID:0111984
UMLS	C4748304
MedGen	1648422
GARD	0017981
Is cancer (heuristic)	no

Also known as: IMD58 · immunodeficiency 58

Data availability: 46 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 › autosomal genetic disease › autosomal recessive disease › severe combined immunodeficiency due to CARMIL2 deficiency

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

46 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 7 likely pathogenic, 7 pathogenic, 3 benign/likely benign, 3 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 2 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177520	NM_001013838.3(CARMIL2):c.520C>T (p.Arg174Ter)	CARMIL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
266035	NM_001013838.3(CARMIL2):c.490dup (p.Ala164fs)	CARMIL2	Pathogenic	no assertion criteria provided
266036	NM_001013838.3(CARMIL2):c.871+1G>T	CARMIL2	Pathogenic	criteria provided, multiple submitters, no conflicts
3689686	NM_001013838.3(CARMIL2):c.4135C>T (p.Gln1379Ter)	CARMIL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4530587	NM_001013838.3(CARMIL2):c.3120+1G>A	CARMIL2	Pathogenic	criteria provided, single submitter
562177	NM_001013838.3(CARMIL2):c.1590C>A (p.Asn530Lys)	CARMIL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
565279	NM_001013838.3(CARMIL2):c.1574T>A (p.Leu525Gln)	CARMIL2	Pathogenic	no assertion criteria provided
565280	NM_001013838.3(CARMIL2):c.2557C>T (p.Gln853Ter)	CARMIL2	Pathogenic	criteria provided, single submitter
565284	NM_001013838.3(CARMIL2):c.2536_2548del (p.Leu846fs)	CARMIL2	Pathogenic	criteria provided, single submitter
977751	NM_001013838.3(CARMIL2):c.1784del (p.Lys595fs)	CARMIL2	Pathogenic	criteria provided, multiple submitters, no conflicts
1333422	NM_001013838.3(CARMIL2):c.2313+1G>A	CARMIL2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339528	NM_001013838.3(CARMIL2):c.1334+1G>T	CARMIL2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2585317	NM_001013838.3(CARMIL2):c.1528C>T (p.Gln510Ter)	CARMIL2	Likely pathogenic	criteria provided, single submitter
2690559	NM_001013838.3(CARMIL2):c.1753_1754del (p.Gln585fs)	CARMIL2	Likely pathogenic	criteria provided, single submitter
565278	NM_001013838.3(CARMIL2):c.1115T>G (p.Leu372Arg)	CARMIL2	Likely pathogenic	criteria provided, single submitter
565285	NM_001013838.3(CARMIL2):c.149G>C (p.Arg50Thr)	CARMIL2	Likely pathogenic	criteria provided, single submitter
982945	NM_001013838.3(CARMIL2):c.958+1G>C	CARMIL2	Likely pathogenic	criteria provided, single submitter
1581961	NM_001013838.3(CARMIL2):c.1554C>G (p.Asp518Glu)	CARMIL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1585289	NM_001013838.3(CARMIL2):c.1308C>G (p.Asp436Glu)	CARMIL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
565281	NM_001013838.3(CARMIL2):c.1916T>A (p.Leu639His)	CARMIL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
636843	NM_001013838.3(CARMIL2):c.4226C>G (p.Pro1409Arg)	ACD	Uncertain significance	criteria provided, multiple submitters, no conflicts
1006305	NM_001013838.3(CARMIL2):c.2659G>A (p.Ala887Thr)	CARMIL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028933	NM_001013838.3(CARMIL2):c.3827G>A (p.Arg1276Lys)	CARMIL2	Uncertain significance	criteria provided, single submitter
1028934	NM_001013838.3(CARMIL2):c.745G>A (p.Glu249Lys)	CARMIL2	Uncertain significance	criteria provided, single submitter
1063548	NM_001013838.3(CARMIL2):c.226G>A (p.Ala76Thr)	CARMIL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1391820	NM_001013838.3(CARMIL2):c.415C>T (p.Arg139Trp)	CARMIL2	Uncertain significance	criteria provided, single submitter
1448554	NM_001013838.3(CARMIL2):c.1937G>A (p.Arg646Gln)	CARMIL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1450720	NM_001013838.3(CARMIL2):c.2413C>T (p.Arg805Cys)	CARMIL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1676252	NM_001013838.3(CARMIL2):c.926T>C (p.Leu309Pro)	CARMIL2	Uncertain significance	criteria provided, single submitter
1705623	NM_001013838.3(CARMIL2):c.473T>G (p.Phe158Cys)	CARMIL2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 4 · 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
CARMIL2	Strong	Autosomal recessive	severe combined immunodeficiency due to CARMIL2 deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CARMIL2	Orphanet:542301	EBV-induced lymphoproliferative disease due to CARMIL2 deficiency
ACD	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
ACD	Orphanet:397692	Hereditary isolated aplastic anemia
ACD	Orphanet:618	Familial melanoma

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
CARMIL2	HGNC:27089	ENSG00000159753	Q6F5E8	Capping protein, Arp2/3 and myosin-I linker protein 2	gencc,clinvar
ACD	HGNC:25070	ENSG00000102977	Q96AP0	Adrenocortical dysplasia protein homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
ACD	Adrenocortical dysplasia protein homolog	Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CARMIL2	Other/Unknown	no		Leu-rich_rpt, PH-like_dom_sf, CARMIL_C
ACD	Other/Unknown	no		TPP1/Est3, ACD

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right hemisphere of cerebellum	2
anterior cingulate cortex	1
right frontal lobe	1
cerebellar cortex	1
cerebellar hemisphere	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CARMIL2	183	ubiquitous	yes	right frontal lobe, anterior cingulate cortex, right hemisphere of cerebellum
ACD	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACD	1,044
CARMIL2	645

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACD	Q96AP0	19

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CARMIL2	Q6F5E8	61.50

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 2 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
Depurination	1	1631.4×	0.005	ACD
Depyrimidination	1	951.7×	0.005	ACD
Base-Excision Repair, AP Site Formation	1	878.5×	0.005	ACD
Telomere C-strand synthesis initiation	1	815.7×	0.005	ACD
Processive synthesis on the C-strand of the telomere	1	761.3×	0.005	ACD
Telomere C-strand (Lagging Strand) Synthesis	1	761.3×	0.005	ACD
Base Excision Repair	1	713.8×	0.005	ACD
Removal of the Flap Intermediate from the C-strand	1	634.4×	0.005	ACD
Extension of Telomeres	1	601.0×	0.005	ACD
Telomere Extension By Telomerase	1	456.8×	0.006	ACD
Polymerase switching on the C-strand of the telomere	1	423.0×	0.006	ACD
Telomere Maintenance	1	368.4×	0.006	ACD
Meiosis	1	285.5×	0.008	ACD
Packaging Of Telomere Ends	1	219.6×	0.008	ACD
Chromosome Maintenance	1	211.5×	0.008	ACD
Recognition and association of DNA glycosylase with site containing an affected purine	1	203.9×	0.008	ACD
Cleavage of the damaged purine	1	203.9×	0.008	ACD
Reproduction	1	190.3×	0.008	ACD
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	1	184.2×	0.008	ACD
Cleavage of the damaged pyrimidine	1	184.2×	0.008	ACD
Inhibition of DNA recombination at telomere	1	167.9×	0.008	ACD
DNA Damage/Telomere Stress Induced Senescence	1	163.1×	0.008	ACD
Meiotic synapsis	1	141.0×	0.008	ACD
Cellular Senescence	1	137.6×	0.008	ACD
DNA Repair	1	98.5×	0.011	ACD
Cellular responses to stress	1	36.8×	0.029	ACD
Cell Cycle	1	36.0×	0.029	ACD
Cellular responses to stimuli	1	31.5×	0.032	ACD

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
establishment or maintenance of monopolar cell polarity	1	8426.0×	0.002	CARMIL2
segmentation	1	4213.0×	0.002	ACD
positive regulation of lamellipodium organization	1	4213.0×	0.002	CARMIL2
regulation of establishment of protein localization to telomere	1	2808.7×	0.002	ACD
telomere assembly	1	2106.5×	0.002	ACD
negative regulation of barbed-end actin filament capping	1	2106.5×	0.002	CARMIL2
protection from non-homologous end joining at telomere	1	1203.7×	0.003	ACD
establishment of protein localization to telomere	1	1053.2×	0.003	ACD
actin filament network formation	1	936.2×	0.003	CARMIL2
protein localization to chromosome, telomeric region	1	766.0×	0.003	ACD
telomere capping	1	648.1×	0.003	ACD
positive regulation of extracellular matrix disassembly	1	601.9×	0.003	CARMIL2
wound healing, spreading of cells	1	561.7×	0.003	CARMIL2
regulation of Arp2/3 complex-mediated actin nucleation	1	526.6×	0.003	CARMIL2
urogenital system development	1	495.6×	0.003	ACD
positive regulation of ruffle assembly	1	495.6×	0.003	CARMIL2
telomere maintenance via telomerase	1	366.4×	0.004	ACD
negative regulation of telomere maintenance via telomerase	1	366.4×	0.004	ACD
positive regulation of lamellipodium assembly	1	300.9×	0.005	CARMIL2
positive regulation of telomere maintenance	1	255.3×	0.005	ACD
establishment or maintenance of cell polarity	1	200.6×	0.006	CARMIL2
embryonic limb morphogenesis	1	200.6×	0.006	ACD
telomere maintenance	1	133.8×	0.009	ACD
skeletal system development	1	62.9×	0.018	ACD
intracellular protein transport	1	32.4×	0.032	ACD
positive regulation of cell migration	1	30.9×	0.032	CARMIL2
cell migration	1	30.8×	0.032	CARMIL2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CARMIL2	0	0
ACD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CARMIL2, ACD

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CARMIL2	0	—
ACD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.