TMEM237

Summary

TMEM237 (transmembrane protein 237, HGNC:14432) is a protein-coding gene on chromosome 2q33.1, encoding Transmembrane protein 237 (Q96Q45). Component of the transition zone in primary cilia.

The protein encoded by this gene is a tetraspanin protein that is thought to be involved in WNT signaling. Defects in this gene are a cause of Joubert syndrome-14. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 65062 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 14 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 519 total — 23 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 114
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001044385

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14432
Approved symbol	TMEM237
Name	transmembrane protein 237
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	JBTS14
Ensembl gene	ENSG00000155755
Ensembl biotype	protein_coding
OMIM	614423
Entrez	65062

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 3 protein_coding, 3 retained_intron

ENST00000286196, ENST00000409444, ENST00000409883, ENST00000432684, ENST00000444047, ENST00000463205, ENST00000466641, ENST00000466839, ENST00000471318, ENST00000480124, ENST00000489550, ENST00000495329, ENST00000621467, ENST00000686475

RefSeq mRNA: 2 — MANE Select: NM_001044385 NM_001044385, NM_152388

CCDS: CCDS46489, CCDS46490

Canonical transcript exons

ENST00000409883 — 13 exons

Exon	Start	End
ENSE00001581076	201643359	201643503
ENSE00003468570	201640261	201640265
ENSE00003500612	201627321	201627414
ENSE00003532181	201636748	201636885
ENSE00003534818	201629729	201629852
ENSE00003536413	201638989	201639045
ENSE00003555390	201629230	201629421
ENSE00003579492	201628076	201628149
ENSE00003583758	201633311	201633431
ENSE00003591858	201632051	201632208
ENSE00003615526	201626026	201626147
ENSE00003648089	201640893	201640924
ENSE00003843253	201620186	201624322

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.0378 / max 236.3776, expressed in 1730 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33243	11.2243	1607
33241	5.4774	1465
33244	0.7263	392
33242	0.6478	369
33238	0.3337	121
33240	0.2850	118
33245	0.2391	132
33239	0.1042	22

Top tissues by expression

259 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.18	gold quality
adrenal tissue	UBERON:0018303	96.21	gold quality
ventricular zone	UBERON:0003053	93.80	gold quality
skin of abdomen	UBERON:0001416	93.30	gold quality
ganglionic eminence	UBERON:0004023	93.12	gold quality
embryo	UBERON:0000922	93.11	gold quality
skin of leg	UBERON:0001511	92.61	gold quality
descending thoracic aorta	UBERON:0002345	92.02	gold quality
thoracic aorta	UBERON:0001515	92.00	gold quality
ascending aorta	UBERON:0001496	91.95	gold quality
zone of skin	UBERON:0000014	91.63	gold quality
tendon	UBERON:0000043	91.56	gold quality
aorta	UBERON:0000947	90.31	gold quality
popliteal artery	UBERON:0002250	89.30	gold quality
upper arm skin	UBERON:0004263	89.30	gold quality
tibial artery	UBERON:0007610	89.29	gold quality
right coronary artery	UBERON:0001625	89.14	gold quality
stromal cell of endometrium	CL:0002255	89.06	gold quality
sperm	CL:0000019	88.69	silver quality
esophagus mucosa	UBERON:0002469	88.26	gold quality
right adrenal gland	UBERON:0001233	88.14	gold quality
left ovary	UBERON:0002119	88.09	gold quality
right adrenal gland cortex	UBERON:0035827	88.06	gold quality
left adrenal gland	UBERON:0001234	88.00	gold quality
left coronary artery	UBERON:0001626	87.96	gold quality
right ovary	UBERON:0002118	87.95	gold quality
left adrenal gland cortex	UBERON:0035825	87.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.66	gold quality
adrenal gland	UBERON:0002369	87.66	gold quality
muscle of leg	UBERON:0001383	87.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

148 targeting TMEM237, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 2)

• TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone (PMID:22152675)
• TMEM237 in HuTu-80 cells led to a significant induction in riboflavin uptake. Transfecting TMEM237 into HuTu-80 cells led to a marked enhancement in hRFVT-3 protein stability (reflected by an increase in protein half-life). (PMID:30892938)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem237a	ENSDARG00000041735
danio_rerio	tmem237b	ENSDARG00000074248
mus_musculus	Tmem237	ENSMUSG00000038079
rattus_norvegicus	Tmem237	ENSRNOG00000024085

Protein

Protein identifiers

Transmembrane protein 237 — Q96Q45 (reviewed: Q96Q45)

Alternative names: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 4 protein

All UniProt accessions (4): Q96Q45, A0A087WWU1, F2Z329, F8WE96

UniProt curated annotations — full annotation on UniProt →

Function. Component of the transition zone in primary cilia. Required for ciliogenesis.

Subunit / interactions. Part of the tectonic-like complex (also named B9 complex). Interacts with TMEM107.

Subcellular location. Membrane. Cell projection. Cilium.

Disease relevance. Joubert syndrome 14 (JBTS14) [MIM:614424] An autosomal recessive disorder characterized by severe intellectual disability, hypotonia, breathing abnormalities in infancy, and dysmorphic facial features. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include renal disease, abnormal eye movements, and postaxial polydactyly. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TMEM237 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96Q45-1	1	yes
Q96Q45-2	2
Q96Q45-3	3
Q96Q45-4	4
Q96Q45-5	5

RefSeq proteins (2): NP_001037850, NP_689601 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029409	TMEM237	Family

Pfam: PF15383

UniProt features (21 total): sequence conflict 5, transmembrane region 4, splice variant 4, compositionally biased region 3, modified residue 2, chain 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q45-F1	63.79	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 49, 25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 358 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, PATIL_LIVER_CANCER, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, LIAO_METASTASIS, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, GCM_MAP1B, LEIN_CHOROID_PLEXUS_MARKERS, GOCC_CILIARY_TRANSITION_ZONE, GOCC_PHOTORECEPTOR_CONNECTING_CILIUM

GO Biological Process (3): regulation of Wnt signaling pathway (GO:0030111), cilium assembly (GO:0060271), cell projection organization (GO:0030030)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), nuclear speck (GO:0016607), photoreceptor connecting cilium (GO:0032391), ciliary transition zone (GO:0035869), cone photoreceptor outer segment (GO:0120199), rod photoreceptor outer segment (GO:0120200), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
photoreceptor outer segment	2
regulation of signal transduction	1
Wnt signaling pathway	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cellular component organization	1
binding	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
nuclear ribonucleoprotein granule	1
ciliary transition zone	1
photoreceptor cell cilium	1
cilium	1

Protein interactions and networks

STRING

1886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM237	TMEM67	Q5HYA8	939
TMEM237	TMEM231	Q9H6L2	924
TMEM237	B9D1	Q9UPM9	887
TMEM237	NPHP1	O15259	877
TMEM237	CC2D2A	Q9P2K1	872
TMEM237	TMEM216	Q9P0N5	870
TMEM237	TMEM17	Q86X19	867
TMEM237	RPGRIP1L	Q68CZ1	866
TMEM237	TCTN1	Q2MV58	862
TMEM237	B9D2	Q9BPU9	854
TMEM237	NPHP4	O75161	833
TMEM237	TCTN3	Q6NUS6	829
TMEM237	TCTN2	Q96GX1	819
TMEM237	CEP290	O15078	810
TMEM237	TMEM107	Q6UX40	795

IntAct

31 interactions, top by confidence:

A	B	Type	Score
NPHP1	NPHP4	psi-mi:“MI:2364”(proximity)	0.930
NPHP1	NPHP4	psi-mi:“MI:0914”(association)	0.930
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TMEM237	CLGN	psi-mi:“MI:0914”(association)	0.530
CFTR	TMEM237	psi-mi:“MI:0915”(physical association)	0.520
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
Dlg4	TMEM237	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM107	TMEM237	psi-mi:“MI:0915”(physical association)	0.400
	SHTN1	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
RXFP1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
RPL3	GTPBP10	psi-mi:“MI:0914”(association)	0.350
SLC16A5	NDUFB3	psi-mi:“MI:0914”(association)	0.350
SLC6A7	ABCB1	psi-mi:“MI:0914”(association)	0.350
UNC93A	HAT1	psi-mi:“MI:0914”(association)	0.350
NPHP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TMEM237	SRPRA	psi-mi:“MI:2364”(proximity)	0.270
TMEM237	EMC8	psi-mi:“MI:2364”(proximity)	0.270
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TMEM237	CMTM6	psi-mi:“MI:0915”(physical association)	0.000
TMEM237	PRNP	psi-mi:“MI:0407”(direct interaction)	0.000

BioGRID (252): TMEM237 (Affinity Capture-MS), FGB (Affinity Capture-MS), PIGR (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), LTF (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), IGHA1 (Affinity Capture-MS), EPX (Affinity Capture-MS), IGJ (Affinity Capture-MS), TMEM237 (Proximity Label-MS), BCAP31 (Proximity Label-MS), CCDC47 (Proximity Label-MS), CKAP4 (Proximity Label-MS)

ESM2 similar proteins: A0A2R8Q3S9, A2VCV0, A9ULX8, E1BN97, F1NVK6, F6UF99, P28236, P79169, P79368, Q06220, Q09108, Q0P557, Q0VA42, Q1LZF8, Q28132, Q29030, Q2T9I9, Q3B7T8, Q3V0J1, Q5PQX1, Q5R6R3, Q5T5J6, Q5ZM60, Q640L3, Q640U0, Q66H73, Q6PAV5, Q6PG04, Q7ZX27, Q7ZXV6, Q8K4Q9, Q8N4S0, Q8TDY2, Q90314, Q90WN7, Q91892, Q921T2, Q95M19, Q95MD2, Q95N18

Diamond homologs: A9ULX8, E1BN97, F1NVK6, F1Q930, F6UF99, Q3V0J1, Q66IE4, Q96Q45

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

519 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	14
Uncertain significance	254
Likely benign	152
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065465	NM_001044385.3(TMEM237):c.869+1del	Pathogenic
1069606	NM_001044385.3(TMEM237):c.605_606del (p.Ile202fs)	Pathogenic
1072229	NC_000002.11:g.(?202466462)(202508123_?)del	Pathogenic
1075598	NM_001044385.3(TMEM237):c.890C>G (p.Ser297Ter)	Pathogenic
1403232	NM_001044385.3(TMEM237):c.325C>T (p.Arg109Ter)	Pathogenic
1430872	NM_001044385.3(TMEM237):c.278T>A (p.Leu93Ter)	Pathogenic
1452907	NM_001044385.3(TMEM237):c.606_609dup (p.Val204fs)	Pathogenic
1455230	NM_001044385.3(TMEM237):c.314C>G (p.Ser105Ter)	Pathogenic
1456904	NM_001044385.3(TMEM237):c.470_473dup (p.Thr159fs)	Pathogenic
2120213	NM_001044385.3(TMEM237):c.128dup (p.Asn43fs)	Pathogenic
2120625	NM_001044385.3(TMEM237):c.694dup (p.Ser232fs)	Pathogenic
2188320	NM_001044385.3(TMEM237):c.413_420del (p.Glu138fs)	Pathogenic
2423584	NC_000002.11:g.(?202508062)(202508123_?)del	Pathogenic
31180	NM_001044385.3(TMEM237):c.52C>T (p.Arg18Ter)	Pathogenic
31181	NM_001044385.3(TMEM237):c.677+1G>T	Pathogenic
31183	NM_001044385.3(TMEM237):c.76C>T (p.Gln26Ter)	Pathogenic
31184	NM_001044385.3(TMEM237):c.943+1G>T	Pathogenic
3236134	NM_001044385.3(TMEM237):c.487C>T (p.Gln163Ter)	Pathogenic
4720598	NM_001044385.3(TMEM237):c.869+1G>T	Pathogenic
4732547	NM_001044385.3(TMEM237):c.658dup (p.Thr220fs)	Pathogenic
596040	NM_001044385.3(TMEM237):c.73dup (p.Ser25fs)	Pathogenic
647195	NM_001044385.3(TMEM237):c.901C>T (p.Arg301Ter)	Pathogenic
692024	NM_001044385.3(TMEM237):c.275-2A>G	Pathogenic
1049742	NM_001044385.3(TMEM237):c.241C>T (p.Gln81Ter)	Likely pathogenic
1683273	NM_001044385.3(TMEM237):c.636G>A (p.Trp212Ter)	Likely pathogenic
2021280	NM_001044385.3(TMEM237):c.396-2A>G	Likely pathogenic
2430689	NM_001044385.3(TMEM237):c.662_669del (p.Val221fs)	Likely pathogenic
2631160	NM_001044385.3(TMEM237):c.673_675delinsAT (p.Phe225fs)	Likely pathogenic
2631730	NM_001044385.3(TMEM237):c.550del (p.Ser184fs)	Likely pathogenic
3064085	NM_001044385.3(TMEM237):c.137-2A>G	Likely pathogenic

SpliceAI

2062 predictions. Top by Δscore:

Variant	Effect	Δscore
2:201624321:CT:C	acceptor_gain	1.0000
2:201628070:A:AC	donor_gain	1.0000
2:201628071:C:CC	donor_gain	1.0000
2:201628074:A:AC	donor_gain	1.0000
2:201628075:C:CC	donor_gain	1.0000
2:201632049:A:AC	donor_gain	1.0000
2:201632049:ACGG:A	donor_gain	1.0000
2:201632050:C:CC	donor_gain	1.0000
2:201632050:CG:C	donor_gain	1.0000
2:201632050:CGG:C	donor_gain	1.0000
2:201632050:CGGC:C	donor_gain	1.0000
2:201632050:CGGCT:C	donor_gain	1.0000
2:201633305:TCCTA:T	donor_loss	1.0000
2:201633306:CCTAC:C	donor_loss	1.0000
2:201633307:CTA:C	donor_loss	1.0000
2:201633308:TA:T	donor_loss	1.0000
2:201633309:A:AC	donor_gain	1.0000
2:201633309:ACT:A	donor_loss	1.0000
2:201633310:C:CC	donor_gain	1.0000
2:201633310:CT:C	donor_gain	1.0000
2:201633318:T:TA	donor_gain	1.0000
2:201633427:CAATT:C	acceptor_gain	1.0000
2:201633429:ATT:A	acceptor_gain	1.0000
2:201633430:TT:T	acceptor_gain	1.0000
2:201633432:C:CC	acceptor_gain	1.0000
2:201633432:C:CG	acceptor_loss	1.0000
2:201636727:AAC:A	donor_gain	1.0000
2:201636728:A:C	donor_gain	1.0000
2:201636743:CATA:C	donor_loss	1.0000
2:201636744:ATAC:A	donor_loss	1.0000

AlphaMissense

2632 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:201632064:A:C	F180L	0.996
2:201632064:A:T	F180L	0.996
2:201632066:A:G	F180L	0.996
2:201629845:G:C	F187L	0.995
2:201629845:G:T	F187L	0.995
2:201629846:A:C	F187C	0.995
2:201629846:A:G	F187S	0.995
2:201629847:A:G	F187L	0.995
2:201626068:A:G	W373R	0.994
2:201626068:A:T	W373R	0.994
2:201632065:A:C	F180C	0.993
2:201626113:A:G	W358R	0.992
2:201626113:A:T	W358R	0.992
2:201629375:A:G	W242R	0.992
2:201629375:A:T	W242R	0.992
2:201627383:A:C	S325R	0.991
2:201627383:A:T	S325R	0.991
2:201627385:T:G	S325R	0.991
2:201629250:A:C	S283R	0.991
2:201629250:A:T	S283R	0.991
2:201629252:T:G	S283R	0.991
2:201632065:A:G	F180S	0.991
2:201629386:C:T	G238D	0.987
2:201632085:G:C	S173R	0.983
2:201632085:G:T	S173R	0.983
2:201632087:T:G	S173R	0.983
2:201629398:C:T	G234E	0.980
2:201627368:A:C	S330R	0.978
2:201627368:A:T	S330R	0.978
2:201627370:T:G	S330R	0.978

dbSNP variants (sampled 300 via entrez): RS1000003070 (2:201624144 T>C,G), RS1000044140 (2:201637703 C>T), RS1000263803 (2:201641532 G>A), RS1000267122 (2:201630736 C>T), RS1000338646 (2:201641191 C>T), RS1000570626 (2:201623376 G>C), RS1000633418 (2:201622649 A>G,T), RS1000681966 (2:201635063 A>G,T), RS1000736184 (2:201628840 C>T), RS1000765936 (2:201628485 G>A), RS1000979385 (2:201622879 A>G), RS1001421624 (2:201623652 C>G), RS1001563823 (2:201640962 C>A), RS1001725124 (2:201622800 T>C), RS1001788336 (2:201621722 G>C)

Disease associations

OMIM: gene MIM:614423 | disease phenotypes: MIM:614424, MIM:249000, MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 14	Definitive	Autosomal recessive
Joubert syndrome with renal defect	Supportive	Autosomal recessive
Joubert syndrome with oculorenal defect	Supportive	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive
Meckel syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Joubert syndrome 14	Definitive	AR

Mondo (8): Joubert syndrome 14 (MONDO:0013745), Joubert syndrome and related disorders (MONDO:0015369), Meckel syndrome (MONDO:0018921), Joubert syndrome 1 (MONDO:0008944), Joubert syndrome (MONDO:0018772), inherited retinal dystrophy (MONDO:0019118), Joubert syndrome with renal defect (MONDO:0012308), Joubert syndrome with oculorenal defect (MONDO:0009480)

Orphanet (4): Joubert syndrome and related disorders (Orphanet:140874), Meckel syndrome (Orphanet:564), Isolated Joubert syndrome (Orphanet:475), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

114 total (30 of 114 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000037	Male pseudohermaphroditism
HP:0000062	Ambiguous genitalia
HP:0000068	Urethral atresia
HP:0000073	Ureteral duplication
HP:0000083	Renal insufficiency
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000175	Cleft palate
HP:0000194	Open mouth
HP:0000202	Orofacial cleft
HP:0000221	Furrowed tongue
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004748_75	Lung cancer	7.000000e-06
GCST004749_89	Lung cancer in ever smokers	1.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C537430	Arima syndrome (supp.)
C536296	Joubert syndrome 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Cisplatin	affects cotreatment, increases expression	2
Tretinoin	decreases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects methylation	1
cobaltous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	decreases expression	1
Azathioprine	decreases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	decreases expression	1

Clinical trials (associated diseases)

42 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases