Autosomal recessive nonsyndromic hearing loss 63

Summary

Autosomal recessive nonsyndromic hearing loss 63 (MONDO:0012670) is a disease caused by LRTOMT (GenCC Definitive), with 5 cohort genes.

At a glance

• Causal gene: LRTOMT (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 102

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 63
Mondo ID	MONDO:0012670
MeSH	C566951
OMIM	611451
DOID	DOID:0110515
UMLS	C1969621
MedGen	409872
GARD	0022627
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 63 · autosomal recessive nonsyndromic deafness 63 · autosomal recessive nonsyndromic deafness caused by mutation in LRTOMT · autosomal recessive nonsyndromic deafness type 63 · autosomal recessive nonsyndromic hearing loss 63 · deafness, autosomal recessive 63 · deafness, autosomal recessive type 63 · DFNB63 · LRTOMT autosomal recessive nonsyndromic deafness

Data availability: 102 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 › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 63

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

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

102 retrieved; paginated sample, class counts are floors:

67 uncertain significance, 12 pathogenic, 10 conflicting classifications of pathogenicity, 9 likely pathogenic, 2 likely benign, 1 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
208717	NM_001145308.5(LRTOMT):c.614_617dup (p.Ser207fs)	ANAPC15	Pathogenic	criteria provided, multiple submitters, no conflicts
3601219	NM_001145308.5(LRTOMT):c.426T>A (p.Cys142Ter)	ANAPC15	Pathogenic	criteria provided, single submitter
3601221	NM_001145308.5(LRTOMT):c.555+2T>G	ANAPC15	Pathogenic	criteria provided, single submitter
1687602	NM_145309.6(LRRC51):c.340_346del (p.Ile114fs)	LRRC51	Pathogenic	criteria provided, single submitter
179792	NM_001145308.5(LRTOMT):c.358+4A>C	LRTOMT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601216	NM_001145308.5(LRTOMT):c.314G>A (p.Trp105Ter)	LRTOMT	Pathogenic	criteria provided, single submitter
3601217	NM_001145308.5(LRTOMT):c.315G>A (p.Trp105Ter)	LRTOMT	Pathogenic	criteria provided, single submitter
543	NM_001145308.5(LRTOMT):c.242G>A (p.Arg81Gln)	LRTOMT	Pathogenic	criteria provided, multiple submitters, no conflicts
544	NM_001145308.5(LRTOMT):c.313T>C (p.Trp105Arg)	LRTOMT	Pathogenic	no assertion criteria provided
545	NM_001145308.5(LRTOMT):c.328G>A (p.Glu110Lys)	LRTOMT	Pathogenic	no assertion criteria provided
1804950	NM_001145308.5(LRTOMT):c.199C>T (p.Arg67Ter)	TOMT	Pathogenic	criteria provided, single submitter
3601215	NM_001145308.5(LRTOMT):c.307del (p.Asp103fs)	TOMT	Pathogenic	criteria provided, single submitter
546	NM_001145308.5(LRTOMT):c.333C>G (p.Tyr111Ter)	TOMT	Pathogenic	no assertion criteria provided
430723	Multiple alleles		Likely pathogenic	no assertion criteria provided
1705515	NM_001145308.5(LRTOMT):c.566del (p.Ile189fs)	ANAPC15	Likely pathogenic	criteria provided, single submitter
3601220	NM_001145308.5(LRTOMT):c.476T>G (p.Leu159Arg)	ANAPC15	Likely pathogenic	criteria provided, single submitter
3601222	NM_001145308.5(LRTOMT):c.641T>C (p.Leu214Pro)	ANAPC15	Likely pathogenic	criteria provided, single submitter
3601223	NM_001145308.5(LRTOMT):c.849del (p.Gln284fs)	ANAPC15	Likely pathogenic	criteria provided, single submitter
627450	NM_001145308.5(LRTOMT):c.384_385insCTCG (p.Glu129fs)	ANAPC15	Likely pathogenic	no assertion criteria provided
3601218	NM_001145308.5(LRTOMT):c.347G>A (p.Gly116Glu)	LRTOMT	Likely pathogenic	criteria provided, single submitter
632174	NM_001145308.5(LRTOMT):c.172C>T (p.Arg58Ter)	LRTOMT	Likely pathogenic	criteria provided, single submitter
3601214	NM_001145308.5(LRTOMT):c.242G>C (p.Arg81Pro)	TOMT	Likely pathogenic	criteria provided, single submitter
305994	NM_001145308.5(LRTOMT):c.503C>T (p.Thr168Met)	ANAPC15	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305996	NM_001145308.5(LRTOMT):c.585C>T (p.Asp195=)	ANAPC15	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
226718	NM_145309.6(LRRC51):c.352G>C (p.Gly118Arg)	LRRC51	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227535	NM_001145308.5(LRTOMT):c.397G>C (p.Ala133Pro)	LRTOMT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305986	NM_145309.6(LRRC51):c.255C>T (p.Asp85=)	LRTOMT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305991	NM_001145308.5(LRTOMT):c.209G>A (p.Arg70Gln)	LRTOMT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44038	NM_001145308.5(LRTOMT):c.222A>G (p.Ser74=)	LRTOMT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44039	NM_001145308.5(LRTOMT):c.352G>A (p.Val118Ile)	LRTOMT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
LRTOMT	Definitive	Unknown	autosomal recessive nonsyndromic hearing loss 63	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRTOMT	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
NUMA1	Orphanet:520	Acute promyelocytic leukemia

Cohort genes → proteins

5 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRTOMT	HGNC:25033	ENSG00000284922		leucine rich transmembrane and O-methyltransferase domain containing	gencc,clinvar
ANAPC15	HGNC:24531	ENSG00000110200	P60006	Anaphase-promoting complex subunit 15	clinvar
LRRC51	HGNC:55526	ENSG00000184154	Q96E66	Leucine-rich repeat-containing protein 51	clinvar
TOMT	HGNC:55527	ENSG00000284844	Q8WZ04	Transmembrane O-methyltransferase	clinvar
NUMA1	HGNC:8059	ENSG00000137497	Q14980	Nuclear mitotic apparatus protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANAPC15	Anaphase-promoting complex subunit 15	Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.
TOMT	Transmembrane O-methyltransferase	Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones.
NUMA1	Nuclear mitotic apparatus protein 1	Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 5 · 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	5	1.8×	0.054

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRTOMT	Other/Unknown	no
ANAPC15	Other/Unknown	no		ANAPC15
LRRC51	Other/Unknown	no		Leu-rich_rpt, LRR_dom_sf
TOMT	Other/Unknown	no		SAM_O-MeTrfase, SAM-dependent_MTases_sf
NUMA1	Other/Unknown	no		NuMA_N_HOOK, NuMA_LGNBD, MT-Golgi_org_protein

Expression context

Cohort genes with no expression data: 0.

3 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)	1
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right testis	3
left testis	2
right uterine tube	2
male germ line stem cell (sensu Vertebrata) in testis	1
testis	1
apex of heart	1
bone marrow cell	1
primordial germ cell in gonad	1
ventricular zone	1
body of uterus	1
endocervix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRTOMT	130	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, right testis, testis
ANAPC15	276	ubiquitous	marker	apex of heart, right testis, left testis
LRRC51	136	ubiquitous	marker	right testis, left testis, right uterine tube
TOMT	14		yes	primordial germ cell in gonad, bone marrow cell, ventricular zone
NUMA1	294	ubiquitous	marker	right uterine tube, body of uterus, endocervix

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUMA1	4,282
TOMT	1,448
ANAPC15	937
LRRC51	720
LRTOMT	0

Intra-cohort edges

A	B	Sources
LRRC51	LRTOMT	biogrid_interaction
LRTOMT	TOMT	biogrid_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANAPC15	P60006	18
NUMA1	Q14980	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRRC51	Q96E66	91.31
TOMT	Q8WZ04	90.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 46. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Enzymatic degradation of dopamine by COMT	2	1903.3×	1e-05	LRTOMT, LRRC51
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	1	158.6×	0.030	ANAPC15
Phosphorylation of the APC/C	1	135.9×	0.030	ANAPC15
Inactivation of APC/C via direct inhibition of the APC/C complex	1	129.8×	0.030	ANAPC15
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	1	129.8×	0.030	ANAPC15
Aberrant regulation of mitotic exit in cancer due to RB1 defects	1	129.8×	0.030	ANAPC15
APC/C:Cdc20 mediated degradation of Cyclin B	1	114.2×	0.030	ANAPC15
APC-Cdc20 mediated degradation of Nek2A	1	105.7×	0.030	ANAPC15
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1	105.7×	0.030	ANAPC15
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1	102.0×	0.030	ANAPC15
Aberrant regulation of mitotic cell cycle due to RB1 defects	1	102.0×	0.030	ANAPC15
Diseases of mitotic cell cycle	1	98.5×	0.030	ANAPC15
Mitotic Prophase	1	92.1×	0.030	NUMA1
APC/C:Cdc20 mediated degradation of mitotic proteins	1	89.2×	0.030	ANAPC15
APC/C-mediated degradation of cell cycle proteins	1	84.0×	0.030	ANAPC15
Regulation of mitotic cell cycle	1	84.0×	0.030	ANAPC15
DNA Replication Pre-Initiation	1	79.3×	0.030	ANAPC15
Regulation of APC/C activators between G1/S and early anaphase	1	77.2×	0.030	ANAPC15
Switching of origins to a post-replicative state	1	75.1×	0.030	ANAPC15
Synthesis of DNA	1	75.1×	0.030	ANAPC15
Transcriptional Regulation by VENTX	1	66.4×	0.033	ANAPC15
DNA Replication	1	59.5×	0.035	ANAPC15
Autodegradation of Cdh1 by Cdh1:APC/C	1	47.6×	0.038	ANAPC15
APC/C:Cdc20 mediated degradation of Securin	1	47.6×	0.038	ANAPC15
S Phase	1	45.3×	0.038	ANAPC15
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	1	43.3×	0.038	ANAPC15
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1	42.6×	0.038	ANAPC15
CDK-mediated phosphorylation and removal of Cdc6	1	42.6×	0.038	ANAPC15
Mitotic Spindle Checkpoint	1	39.6×	0.040	ANAPC15
Assembly of the pre-replicative complex	1	34.8×	0.043	ANAPC15

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
anastral spindle assembly	1	5617.3×	0.002	NUMA1
positive regulation of protein localization to spindle pole body	1	5617.3×	0.002	NUMA1
positive regulation of mitotic spindle elongation	1	5617.3×	0.002	NUMA1
catecholamine catabolic process	1	2808.7×	0.003	TOMT
regulation of metaphase plate congression	1	1123.5×	0.004	NUMA1
positive regulation of protein localization to cell cortex	1	1123.5×	0.004	NUMA1
positive regulation of hair follicle development	1	802.5×	0.004	NUMA1
regulation of mitotic cell cycle spindle assembly checkpoint	1	702.2×	0.004	ANAPC15
positive regulation of spindle assembly	1	702.2×	0.004	NUMA1
auditory receptor cell development	1	624.1×	0.004	TOMT
positive regulation of intracellular transport	1	561.7×	0.004	NUMA1
dopamine catabolic process	1	561.7×	0.004	TOMT
positive regulation of chromosome separation	1	561.7×	0.004	NUMA1
cell division	2	30.8×	0.004	ANAPC15, NUMA1
astral microtubule organization	1	432.1×	0.005	NUMA1
positive regulation of chromosome segregation	1	432.1×	0.005	NUMA1
dopamine metabolic process	1	330.4×	0.006	TOMT
regulation of mitotic spindle organization	1	280.9×	0.006	NUMA1
protein branched polyubiquitination	1	280.9×	0.006	ANAPC15
positive regulation of keratinocyte differentiation	1	267.5×	0.006	NUMA1
regulation of meiotic cell cycle	1	255.3×	0.006	ANAPC15
anaphase-promoting complex-dependent catabolic process	1	234.1×	0.006	ANAPC15
positive regulation of microtubule polymerization	1	224.7×	0.006	NUMA1
developmental process	1	224.7×	0.006	TOMT
nucleus organization	1	187.2×	0.007	NUMA1
microtubule bundle formation	1	170.2×	0.008	NUMA1
establishment of mitotic spindle orientation	1	160.5×	0.008	NUMA1
positive regulation of BMP signaling pathway	1	151.8×	0.008	NUMA1
protein K11-linked ubiquitination	1	130.6×	0.009	ANAPC15
meiotic cell cycle	1	81.4×	0.014	NUMA1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NUMA1	1	2
LRTOMT	0	0
ANAPC15	0	0
LRRC51	0	0
TOMT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	NUMA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NUMA1	8	Binding:8

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

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	NUMA1

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	1	NUMA1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	LRTOMT, ANAPC15, LRRC51, TOMT

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LRTOMT	0	—
ANAPC15	0	—
LRRC51	0	—
TOMT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.