Orofaciodigital syndrome type 6

Summary

Orofaciodigital syndrome type 6 (MONDO:0010176) is a disease caused by CPLANE1 (GenCC Definitive), with 8 cohort genes. The dominant Reactome pathway is Anchoring of the basal body to the plasma membrane (3 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CPLANE1 (GenCC Definitive)
• Cohort genes: 8
• ClinVar variants: 620
• Phenotypes (HPO): 52

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000180	Lobulated tongue	Frequent (30-79%)
HP:0000190	Abnormal oral frenulum morphology	Frequent (30-79%)
HP:0000199	Tongue nodules	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000276	Long face	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000405	Conductive hearing impairment	Frequent (30-79%)
HP:0000455	Broad nasal tip	Frequent (30-79%)
HP:0000565	Esotropia	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001159	Syndactyly	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002419	Molar tooth sign on MRI	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004422	Biparietal narrowing	Frequent (30-79%)
HP:0007036	Hypoplasia of olfactory tract	Frequent (30-79%)
HP:0008689	Bilateral cryptorchidism	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0011802	Hamartoma of tongue	Frequent (30-79%)
HP:0040019	Finger clinodactyly	Frequent (30-79%)
HP:0100258	Preaxial polydactyly	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000104	Renal agenesis	Occasional (5-29%)
HP:0000426	Prominent nasal bridge	Occasional (5-29%)
HP:0001161	Hand polydactyly	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001320	Cerebellar vermis hypoplasia	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0001829	Foot polydactyly	Occasional (5-29%)
HP:0002104	Apnea	Occasional (5-29%)
HP:0002269	Abnormality of neuronal migration	Occasional (5-29%)
HP:0002444	Hypothalamic hamartoma	Occasional (5-29%)
HP:0002553	Highly arched eyebrow	Occasional (5-29%)
HP:0002876	Episodic tachypnea	Occasional (5-29%)
HP:0006145	Central Y-shaped metacarpal	Occasional (5-29%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0008678	Renal hypoplasia/aplasia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	orofaciodigital syndrome type 6
Mondo ID	MONDO:0010176
MeSH	C536531
OMIM	277170
Orphanet	2754
DOID	DOID:0060376
NCIT	C124841
SNOMED CT	721873007
UMLS	C2745997
MedGen	411200
GARD	0004412
Is cancer (heuristic)	no

Also known as: Joubert syndrome with oral-facial-digital syndrome · Joubert syndrome with orofaciodigital defect · OFD6 · oral-facial-digital syndrome type 6 · orofaciodigital syndrome type 6 · orofaciodigital syndrome VI · polydactyly - cleft lip/palate - psychomotor retardation · polydactyly cleft lip palate psychomotor retardation · polydactyly-cleft lip/palate-psychomotor retardation syndrome · Varadi syndrome · Varadi-Papp syndrome · Váradi syndrome · Váradi-Papp syndrome

Data availability: 620 ClinVar variants · 10 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 17 › orofaciodigital syndrome type 6

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:

386 uncertain significance, 57 likely pathogenic, 39 likely benign, 38 conflicting classifications of pathogenicity, 36 pathogenic/likely pathogenic, 27 pathogenic, 14 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1030823	NM_001384732.1(CPLANE1):c.9046C>T (p.Arg3016Ter)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1202647	NM_001384732.1(CPLANE1):c.6354dup (p.Ile2119fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1369735	NM_001384732.1(CPLANE1):c.6477del (p.Ser2160fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1416162	NM_001384732.1(CPLANE1):c.3599C>A (p.Ala1200Glu)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1444291	NM_001384732.1(CPLANE1):c.3829dup (p.Cys1277fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451420	NM_001384732.1(CPLANE1):c.7402C>T (p.Gln2468Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
1455619	NM_001384732.1(CPLANE1):c.5594dup (p.Asn1865fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
1456393	NM_001384732.1(CPLANE1):c.7032del (p.Lys2345fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
157512	NM_001384732.1(CPLANE1):c.3150-1G>T	CPLANE1	Pathogenic	criteria provided, single submitter
157513	NM_001384732.1(CPLANE1):c.493del (p.Ile165fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
157514	NM_001384732.1(CPLANE1):c.3290-2A>G	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
157515	NM_001384732.1(CPLANE1):c.3380C>T (p.Ser1127Leu)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
183307	NM_001384732.1(CPLANE1):c.8150_8151del (p.Gly2717fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
194120	NM_001384732.1(CPLANE1):c.1819dup (p.Tyr607fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217564	NM_001384732.1(CPLANE1):c.9017+1G>A	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217565	NM_001384732.1(CPLANE1):c.8425_8426insG (p.Thr2809fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217566	NM_001384732.1(CPLANE1):c.8140C>T (p.Arg2714Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217569	NM_001384732.1(CPLANE1):c.9220C>T (p.Arg3074Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217571	NM_001384732.1(CPLANE1):c.8872C>T (p.Arg2958Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217574	NM_001384732.1(CPLANE1):c.7778G>A (p.Trp2593Ter)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217575	NM_001384732.1(CPLANE1):c.7871T>A (p.Leu2624Ter)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217577	NM_001384732.1(CPLANE1):c.3130_3131insA (p.Arg1044fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217578	NM_001384732.1(CPLANE1):c.510del (p.Leu171fs)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217580	NM_001384732.1(CPLANE1):c.1784T>G (p.Leu595Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217583	NM_001384732.1(CPLANE1):c.2377C>T (p.Gln793Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217584	NM_001384732.1(CPLANE1):c.2353C>T (p.Arg785Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217585	NM_001384732.1(CPLANE1):c.2709G>A (p.Trp903Ter)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts
217589	NM_001384732.1(CPLANE1):c.2611C>T (p.Arg871Cys)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217590	NM_001384732.1(CPLANE1):c.1819del (p.Tyr607fs)	CPLANE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217591	NM_001384732.1(CPLANE1):c.3599C>T (p.Ala1200Val)	CPLANE1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 62 · Orphanet: 26 · 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
CPLANE1	Definitive	Autosomal recessive	orofaciodigital syndrome type 6	8
OFD1	Definitive	X-linked	orofaciodigital syndrome I	12
TCTN3	Definitive	Autosomal recessive	orofaciodigital syndrome IV	9
KIAA0753	Strong	Autosomal recessive	orofaciodigital syndrome XV	6
FAM149B1	Supportive	Autosomal recessive	orofaciodigital syndrome type 6	6
KIF7	Supportive	Autosomal recessive	orofaciodigital syndrome type 6	10
PDE6D	Supportive	Autosomal recessive	orofaciodigital syndrome type 6	5
TMEM216	Supportive	Autosomal recessive	orofaciodigital syndrome type 6	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CPLANE1	Orphanet:2754	Orofaciodigital syndrome type 6
CPLANE1	Orphanet:475	Isolated Joubert syndrome
CPLANE1	Orphanet:65684	Monomelic amyotrophy
TCTN3	Orphanet:2753	Orofaciodigital syndrome type 4
TCTN3	Orphanet:2754	Orofaciodigital syndrome type 6
TCTN3	Orphanet:475	Isolated Joubert syndrome
TCTN3	Orphanet:564	Meckel syndrome
TMEM216	Orphanet:2318	Joubert syndrome with oculorenal defect
TMEM216	Orphanet:2754	Orofaciodigital syndrome type 6
TMEM216	Orphanet:564	Meckel syndrome
TMEM216	Orphanet:791	Retinitis pigmentosa
OFD1	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:2750	Orofaciodigital syndrome type 1
OFD1	Orphanet:2754	Orofaciodigital syndrome type 6
OFD1	Orphanet:475	Isolated Joubert syndrome
OFD1	Orphanet:791	Retinitis pigmentosa
KIAA0753	Orphanet:2754	Orofaciodigital syndrome type 6
KIAA0753	Orphanet:474	Jeune syndrome
KIAA0753	Orphanet:475	Isolated Joubert syndrome
FAM149B1	Orphanet:2754	Orofaciodigital syndrome type 6
KIF7	Orphanet:166024	Multiple epiphyseal dysplasia-macrocephaly-facial dysmorphism syndrome
KIF7	Orphanet:2189	Hydrolethalus
KIF7	Orphanet:2754	Orofaciodigital syndrome type 6
KIF7	Orphanet:36	Acrocallosal syndrome
PDE6D	Orphanet:2754	Orofaciodigital syndrome type 6
PDE6D	Orphanet:475	Isolated Joubert syndrome

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CPLANE1	HGNC:25801	ENSG00000197603	Q9H799	Ciliogenesis and planar polarity effector 1	gencc,clinvar
TCTN3	HGNC:24519	ENSG00000119977	Q6NUS6	Tectonic-3	gencc
TMEM216	HGNC:25018	ENSG00000187049	Q9P0N5	Transmembrane protein 216	gencc
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	gencc
KIAA0753	HGNC:29110	ENSG00000198920	Q2KHM9	Protein moonraker	gencc
FAM149B1	HGNC:29162	ENSG00000138286	Q96BN6	Primary cilium assembly protein FAM149B1	gencc
KIF7	HGNC:30497	ENSG00000166813	Q2M1P5	Kinesin-like protein KIF7	gencc
PDE6D	HGNC:8788	ENSG00000156973	O43924	Retinal rod rhodopsin-sensitive cGMP 3’,5’-cyclic phosphodiesterase subunit delta	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPLANE1	Ciliogenesis and planar polarity effector 1	Involved in ciliogenesis.
TCTN3	Tectonic-3	Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition.
TMEM216	Transmembrane protein 216	Essential for primary ciliogenesis and embryonic development, facilitating the activation of Hedgehog (Hh) signaling pathway.
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.
KIAA0753	Protein moonraker	Involved in centriole duplication.
FAM149B1	Primary cilium assembly protein FAM149B1	Involved in the localization of proteins to the cilium and cilium assembly.
KIF7	Kinesin-like protein KIF7	Essential for hedgehog signaling regulation: acts both as a negative and positive regulator of sonic hedgehog (Shh) and Indian hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-dependent and -independent mechanisms.
PDE6D	Retinal rod rhodopsin-sensitive cGMP 3’,5’-cyclic phosphodiesterase subunit delta	Promotes the release of prenylated target proteins from cellular membranes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 7 · 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	7	1.6×	0.138
Scaffold/PPI	1	2.2×	0.379

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CPLANE1	Scaffold/PPI	no		CPLANE1, WD40_repeat_dom_sf
TCTN3	Other/Unknown	no		TCTN1-3_dom, TCTN1-3, TCTN1-3_N
TMEM216	Other/Unknown	no		Uncharacterised_TM-17
OFD1	Other/Unknown	no		LisH, OFD1
KIAA0753	Other/Unknown	no		MNR
FAM149B1	Other/Unknown	no		DUF3719, FAM149
KIF7	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
PDE6D	Other/Unknown	no		PDED_dom, Ig_E-set, Rhodop-sen_GMP-Pdiesterase_dsu

Expression context

Cohort genes with no expression data: 0.

7 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1
corpus epididymis	1
decidua	1
stromal cell of endometrium	1
adenohypophysis	1
pituitary gland	1
primordial germ cell in gonad	1
bronchial epithelial cell	1
cervix squamous epithelium	1
sperm	1
cortical plate	1
lower esophagus	1
lower esophagus muscularis layer	1
C1 segment of cervical spinal cord	1
ventricular zone	1
cardiac muscle of right atrium	1
kidney epithelium	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPLANE1	195	ubiquitous	marker	sural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
TCTN3	267	ubiquitous	marker	corpus epididymis, decidua, stromal cell of endometrium
TMEM216	239	ubiquitous	marker	primordial germ cell in gonad, adenohypophysis, pituitary gland
OFD1	288	ubiquitous	marker	sperm, bronchial epithelial cell, cervix squamous epithelium
KIAA0753	243	ubiquitous	marker	cortical plate, lower esophagus, lower esophagus muscularis layer
FAM149B1	265	ubiquitous	marker	C1 segment of cervical spinal cord, ventricular zone, calcaneal tendon
KIF7	165	ubiquitous	yes	kidney epithelium, cardiac muscle of right atrium, left ventricle myocardium
PDE6D	284	ubiquitous	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OFD1	2,878
KIF7	1,655
PDE6D	1,307
KIAA0753	1,062
TCTN3	993
TMEM216	946
FAM149B1	903
CPLANE1	439

Intra-cohort edges

A	B	Sources
CPLANE1	FAM149B1	string_interaction
CPLANE1	OFD1	string_interaction
CPLANE1	TCTN3	string_interaction
CPLANE1	TMEM216	string_interaction
KIAA0753	KIF7	intact
KIAA0753	OFD1	biogrid_interaction, string_interaction
OFD1	TMEM216	string_interaction
TCTN3	TMEM216	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDE6D	O43924	40
KIF7	Q2M1P5	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMEM216	Q9P0N5	89.18
TCTN3	Q6NUS6	71.49
OFD1	O75665	68.41
KIAA0753	Q2KHM9	59.08
FAM149B1	Q96BN6	52.50
CPLANE1	Q9H799

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 8 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring of the basal body to the plasma membrane	3	67.8×	1e-04	TCTN3, TMEM216, OFD1
Hedgehog ‘off’ state	2	71.4×	0.002	OFD1, KIF7
ARL13B-mediated ciliary trafficking of INPP5E	1	761.3×	0.007	PDE6D
RAS processing	1	95.2×	0.039	PDE6D
Signaling by Hedgehog	1	36.8×	0.052	KIF7
Loss of Nlp from mitotic centrosomes	1	31.7×	0.052	OFD1
Loss of proteins required for interphase microtubule organization from the centrosome	1	31.7×	0.052	OFD1
Hedgehog ‘on’ state	1	31.7×	0.052	KIF7
AURKA Activation by TPX2	1	30.4×	0.052	OFD1
Recruitment of mitotic centrosome proteins and complexes	1	27.2×	0.052	OFD1
Regulation of PLK1 Activity at G2/M Transition	1	25.4×	0.052	OFD1
Recruitment of NuMA to mitotic centrosomes	1	23.3×	0.052	OFD1
Cilium Assembly	1	21.8×	0.052	TCTN3
Organelle biogenesis and maintenance	1	13.2×	0.079	TCTN3
Signal Transduction	1	2.0×	0.404	KIF7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cilium assembly	6	55.2×	3e-09	CPLANE1, TCTN3, TMEM216, OFD1, KIAA0753, FAM149B1
positive regulation of smoothened signaling pathway	2	105.3×	0.002	TMEM216, KIF7
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation	1	1053.2×	0.006	OFD1
cytosolic ciliogenesis	1	421.3×	0.011	KIAA0753
photoreceptor cell morphogenesis	1	351.1×	0.011	TMEM216
embryonic body morphogenesis	1	263.3×	0.013	OFD1
epithelial cilium movement involved in determination of left/right asymmetry	1	162.0×	0.018	OFD1
positive regulation of cilium assembly	1	95.8×	0.024	TMEM216
centriole replication	1	91.6×	0.024	KIAA0753
protein localization to centrosome	1	84.3×	0.024	KIAA0753
axoneme assembly	1	68.0×	0.027	OFD1
negative regulation of smoothened signaling pathway	1	56.9×	0.029	KIF7
protein localization to cilium	1	50.1×	0.030	FAM149B1
photoreceptor cell maintenance	1	44.8×	0.032	TMEM216
microtubule-based movement	1	37.0×	0.034	KIF7
non-motile cilium assembly	1	36.3×	0.034	TMEM216
smoothened signaling pathway	1	22.6×	0.051	TCTN3
visual perception	1	9.9×	0.107	PDE6D
positive regulation of apoptotic process	1	7.1×	0.140	TCTN3
apoptotic process	1	3.6×	0.247	TCTN3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 7

Druggability breadth: 2 of 8 evidence-associated genes (25%) 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
PDE6D	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDE6D	8	4
CPLANE1	0	0
TCTN3	0	0
TMEM216	0	0
OFD1	0	0
KIAA0753	0	0
FAM149B1	0	0
KIF7	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARDENAFIL	4	PDE6D
SILDENAFIL	4	PDE6D
TADALAFIL	4	PDE6D
DIPYRIDAMOLE	4	PDE6D
SORAFENIB	4	PDE6D
ROSUVASTATIN	4	PDE6D
ZAPRINAST	2	PDE6D
TBA-7371	2	PDE6D

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PDE6D	147	Binding:145, ADMET:2
KIF7	5	Binding:5

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PDE6D	147

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

8 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)
VARDENAFIL	4	PDE6D
SILDENAFIL	4	PDE6D
TADALAFIL	4	PDE6D
DIPYRIDAMOLE	4	PDE6D
SORAFENIB	4	PDE6D
ROSUVASTATIN	4	PDE6D
ZAPRINAST	2	PDE6D
TBA-7371	2	PDE6D

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDE6D
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	7	CPLANE1, TCTN3, TMEM216, OFD1, KIAA0753, FAM149B1, KIF7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CPLANE1	0	—
TCTN3	0	—
TMEM216	0	—
OFD1	0	—
KIAA0753	0	—
FAM149B1	0	—
KIF7	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.