TMEM216

Summary

TMEM216 (transmembrane protein 216, HGNC:25018) is a protein-coding gene on chromosome 11q13.1, encoding Transmembrane protein 216 (Q9P0N5). Essential for primary ciliogenesis and embryonic development, facilitating the activation of Hedgehog (Hh) signaling pathway.

This locus encodes a transmembrane domain-containing protein. Mutations at this locus have been associated with Meckel-Gruber Syndrome Type 2, and Joubert Syndrome 2, also known as Cerebello-oculorenal Syndrome 2.

Source: NCBI Gene 51259 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 331 total — 19 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 186
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001173990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25018
Approved symbol	TMEM216
Name	transmembrane protein 216
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC13379, HSPC244, JBTS2
Ensembl gene	ENSG00000187049
Ensembl biotype	protein_coding
OMIM	613277
Entrez	51259

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000334888, ENST00000398979, ENST00000515837, ENST00000541473, ENST00000544795, ENST00000684926, ENST00000688959, ENST00000690736, ENST00000909596

RefSeq mRNA: 4 — MANE Select: NM_001173990 NM_001173990, NM_001173991, NM_001330285, NM_016499

CCDS: CCDS53640, CCDS81570, CCDS86205

Canonical transcript exons

ENST00000515837 — 5 exons

Exon	Start	End
ENSE00001234458	61397774	61397975
ENSE00002290263	61398270	61398846
ENSE00002291044	61392587	61392665
ENSE00003540197	61393231	61393332
ENSE00003600435	61393884	61393976

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 90.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.2811 / max 159.3680, expressed in 1693 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114575	5.9813	1591
114576	5.1677	1523
114574	2.3848	954
114577	0.7474	452

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.72	gold quality
adenohypophysis	UBERON:0002196	89.82	gold quality
pituitary gland	UBERON:0000007	89.44	gold quality
left ovary	UBERON:0002119	89.33	gold quality
ventricular zone	UBERON:0003053	89.28	gold quality
right ovary	UBERON:0002118	89.26	gold quality
right uterine tube	UBERON:0001302	88.89	gold quality
ileal mucosa	UBERON:0000331	88.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.61	gold quality
oocyte	CL:0000023	88.40	gold quality
granulocyte	CL:0000094	88.17	gold quality
secondary oocyte	CL:0000655	88.01	gold quality
ovary	UBERON:0000992	87.79	gold quality
endocervix	UBERON:0000458	87.57	gold quality
mucosa of transverse colon	UBERON:0004991	87.01	gold quality
body of pancreas	UBERON:0001150	86.95	gold quality
left uterine tube	UBERON:0001303	86.47	gold quality
islet of Langerhans	UBERON:0000006	86.41	gold quality
pancreatic ductal cell	CL:0002079	85.76	silver quality
bronchial epithelial cell	CL:0002328	85.75	gold quality
rectum	UBERON:0001052	85.74	gold quality
ganglionic eminence	UBERON:0004023	85.70	gold quality
ectocervix	UBERON:0012249	85.69	gold quality
bone marrow	UBERON:0002371	85.62	gold quality
pancreas	UBERON:0001264	85.57	gold quality
right coronary artery	UBERON:0001625	85.48	gold quality
right lobe of thyroid gland	UBERON:0001119	85.40	gold quality
lymph node	UBERON:0000029	85.39	gold quality
spleen	UBERON:0002106	85.36	gold quality
bronchus	UBERON:0002185	85.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting TMEM216, 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-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-1233-5P	98.19	66.71	1201

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 4)

• a TMEM216 mutation may have a role in Joubert syndrome 2 (JBTS2) in Ashkenazi Jews (PMID:20036350)
• Data show that a single G218T mutation (R73L in the protein) was identified in all cases of Ashkenazi Jewish descent. (PMID:20512146)
• study reports that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable ciliopathy, Joubert syndrome; expression of the genes is mediated by a conserved regulatory element in the noncoding intergenic region (PMID:22282472)
• Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression. (PMID:39191256)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem216	ENSDARG00000091576
mus_musculus	Tmem216	ENSMUSG00000024667
rattus_norvegicus	Tmem216	ENSRNOG00000020692
drosophila_melanogaster	TMEM216	FBGN0037614
drosophila_melanogaster	CG11760	FBGN0037615
caenorhabditis_elegans		WBGENE00194710

Paralogs (2): TMEM80 (ENSG00000177042), TMEM17 (ENSG00000186889)

Protein

Protein identifiers

Transmembrane protein 216 — Q9P0N5 (reviewed: Q9P0N5)

All UniProt accessions (4): Q9P0N5, A0A8I5KPG3, A0A8I5QKJ7, J3QT25

UniProt curated annotations — full annotation on UniProt →

Function. Essential for primary ciliogenesis and embryonic development, facilitating the activation of Hedgehog (Hh) signaling pathway. Disrupts the interaction of GLI2 and GLI3 with the negative regulator SUFU. Inhibiting SUFU’s interaction with GLI2 promotes the entry of GLI2 into the nucleus, allowing it to activate Hh target gene expression. Disrupting SUFU’s interaction with GLI3 prevents its conversion into the repressor form, leading to increased nuclear GLI3 and enhanced Hh signaling. Required for the proper development and structural integrity of photoreceptor outer segment disks, ensuring normal outer segment morphogenesis and survival of photoreceptors.

Subunit / interactions. Part of the tectonic-like complex (also named B9 complex). Interacts with TMEM107. Interacts with GLI2 and GLI3, promoting and attenuating their nuclear localization respectively. Interacts with SUFU; this interaction inhibits interaction of SUFU with GLI2 and GLI3.

Subcellular location. Membrane. Cytoplasm. Cytoskeleton. Cilium basal body.

Disease relevance. Joubert syndrome 2 (JBTS2) [MIM:608091] A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. 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 retinal dystrophy and renal disease. The disease is caused by variants affecting the gene represented in this entry. Meckel syndrome 2 (MKS2) [MIM:603194] A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 98 (RP98) [MIM:620996] An autosomal recessive form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP98 is characterized by onset of night blindness in early childhood, with gradual loss of peripheral vision and later of central vision. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. TMEM138 and TMEM216 genes are adjacent and are aligned in a head-to-tail configuration. They share some cis regulatory region and display coordinated expression. Genes were joined by chromosomal rearrangement at the amphiboan to reptile evolutionary transition around 340 million years ago.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P0N5-1	1	yes
Q9P0N5-2	2
Q9P0N5-3	3

RefSeq proteins (4): NP_001167461, NP_001167462, NP_001317214, NP_057583 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019184	Uncharacterised_TM-17	Family

Pfam: PF09799

UniProt features (15 total): sequence variant 6, transmembrane region 4, sequence conflict 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0N5-F1	89.18	0.74

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620912	Anchoring of the basal body to the plasma membrane

MSigDB gene sets: 430 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, KOYAMA_SEMA3B_TARGETS_UP, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_CILIUM_ORGANIZATION, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, GOBP_ORGANELLE_ASSEMBLY

GO Biological Process (7): photoreceptor cell morphogenesis (GO:0008594), photoreceptor cell maintenance (GO:0045494), positive regulation of cilium assembly (GO:0045724), positive regulation of smoothened signaling pathway (GO:0045880), cilium assembly (GO:0060271), non-motile cilium assembly (GO:1905515), cell projection organization (GO:0030030)

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

GO Cellular Component (8): cytosol (GO:0005829), cilium (GO:0005929), membrane (GO:0016020), ciliary transition zone (GO:0035869), MKS complex (GO:0036038), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cilium assembly	2
photoreceptor cell development	1
cell morphogenesis involved in neuron differentiation	1
retina homeostasis	1
multicellular organismal process	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
positive regulation of signal transduction	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
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
protein-containing complex	1
ciliary transition zone	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM216	TMEM67	Q5HYA8	994
TMEM216	CC2D2A	Q9P2K1	988
TMEM216	B9D1	Q9UPM9	980
TMEM216	TCTN1	Q2MV58	976
TMEM216	B9D2	Q9BPU9	966
TMEM216	CEP290	O15078	966
TMEM216	RPGRIP1L	Q68CZ1	957
TMEM216	TMEM231	Q9H6L2	955
TMEM216	TCTN3	Q6NUS6	943
TMEM216	NPHP1	O15259	940
TMEM216	MKS1	Q9NXB0	939
TMEM216	AHI1	Q8N157	930
TMEM216	ARL13B	Q3SXY8	914
TMEM216	TCTN2	Q96GX1	905
TMEM216	OFD1	O75665	876

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TMEM107	TMEM216	psi-mi:“MI:0915”(physical association)	0.400
TMEM216	GPR89A	psi-mi:“MI:2364”(proximity)	0.270
TMEM216	SNAP23	psi-mi:“MI:2364”(proximity)	0.270
TMEM216	MCM3AP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (245): ACBD3 (Proximity Label-MS), ACSL3 (Proximity Label-MS), AGPAT1 (Proximity Label-MS), AGPAT6 (Proximity Label-MS), AGPAT9 (Proximity Label-MS), ALG9 (Proximity Label-MS), ANKLE2 (Proximity Label-MS), ANO10 (Proximity Label-MS), ANO6 (Proximity Label-MS), ARFGAP3 (Proximity Label-MS), ARHGAP1 (Proximity Label-MS), ARL6IP5 (Proximity Label-MS), ATP6AP1 (Proximity Label-MS), ATP6AP2 (Proximity Label-MS), AUP1 (Proximity Label-MS)

ESM2 similar proteins: A0A1B0GVZ9, A4IFN5, A5PK40, A6NH52, A6NI61, B2LYG4, B2RZC9, B6ID01, D2HKB0, D3ZG27, P86229, Q0VDI3, Q15012, Q15546, Q17QJ2, Q1RLT2, Q2TA01, Q4R4I5, Q4R6E8, Q5H8A4, Q5R7Q1, Q5RAH0, Q5RL79, Q5U3C3, Q5VTY9, Q5ZML7, Q64232, Q6PHN7, Q6QRN8, Q719N3, Q71SV0, Q8BWB6, Q8IY49, Q8N6M3, Q8NFT2, Q8R189, Q8VD53, Q8VDI9, Q8VDR5, Q9CQC4

Diamond homologs: A1A4P6, A5D6V4, B6ID01, E1BY51, E7EYQ9, Q2TA01, Q5HZE5, Q96HE8, Q9CQC4, Q9D3H0, Q9P0N5, Q5HZD4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	31
Uncertain significance	108
Likely benign	125
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070704	NM_001173990.3(TMEM216):c.373_374insA (p.Leu125fs)	Pathogenic
1075309	NM_001173990.3(TMEM216):c.249C>A (p.Cys83Ter)	Pathogenic
1418959	NM_001173990.3(TMEM216):c.118_119del (p.Phe40fs)	Pathogenic
1459081	NM_001173990.3(TMEM216):c.75del (p.Phe25_Leu26insTer)	Pathogenic
197	NM_001173990.3(TMEM216):c.218G>T (p.Arg73Leu)	Pathogenic
1970889	NM_001173990.3(TMEM216):c.250C>T (p.Gln84Ter)	Pathogenic
2023018	NM_001173990.3(TMEM216):c.328C>T (p.Gln110Ter)	Pathogenic
2086704	NM_001173990.3(TMEM216):c.360dup (p.Asn121fs)	Pathogenic
2423925	NC_000011.9:g.(?61160094)(61161458_?)del	Pathogenic
2679223	NM_001173990.3(TMEM216):c.222_229+3delinsTTTTTTTGTT	Pathogenic
2705827	NM_001173990.3(TMEM216):c.77_78insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGGAAATCCTGTTCTTTCT (p.Leu26_Asn27insPhePhePhePhePhePheXaaXaaXaaXaaLeuValIleArgProProArgProProLysValLeuGlyLeuGlnAlaTer)	Pathogenic
2743029	NM_001173990.3(TMEM216):c.196del (p.Tyr66fs)	Pathogenic
2759721	NM_001173990.3(TMEM216):c.248_249del (p.Cys83fs)	Pathogenic
2842470	NM_001173990.3(TMEM216):c.236del (p.Lys79fs)	Pathogenic
3370281	NM_001173991.3(TMEM216):c.-69G>T	Pathogenic
3643836	NM_001173990.3(TMEM216):c.135del (p.Gly46fs)	Pathogenic
371710	NM_001173990.3(TMEM216):c.228dup (p.Gly77fs)	Pathogenic
4689395	NM_001173990.3(TMEM216):c.-69G>A	Pathogenic
56384	NM_001173990.3(TMEM216):c.253C>T (p.Arg85Ter)	Pathogenic
1066361	NM_001173990.3(TMEM216):c.137-2A>G	Likely pathogenic
1469730	NM_001173990.3(TMEM216):c.35-1G>A	Likely pathogenic
1494212	NM_001173990.3(TMEM216):c.229+1G>A	Likely pathogenic
1951208	NM_001173990.3(TMEM216):c.229+1G>T	Likely pathogenic
2281809	NM_001173990.3(TMEM216):c.326dup (p.Gln110fs)	Likely pathogenic
2679220	NM_001173990.3(TMEM216):c.86G>A (p.Trp29Ter)	Likely pathogenic
2679221	NM_001173990.3(TMEM216):c.302_303insCATT (p.Met101fs)	Likely pathogenic
2679222	NM_001173990.3(TMEM216):c.229+1G>C	Likely pathogenic
2679224	NM_001173990.3(TMEM216):c.34+1G>A	Likely pathogenic
2679225	NM_001173990.3(TMEM216):c.222_224delinsA (p.Phe76fs)	Likely pathogenic
2679226	NM_001173990.3(TMEM216):c.112G>T (p.Glu38Ter)	Likely pathogenic

SpliceAI

712 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61393879:GGCAG:G	acceptor_loss	1.0000
11:61393880:GCA:G	acceptor_loss	1.0000
11:61393881:CAGG:C	acceptor_loss	1.0000
11:61393882:A:AG	acceptor_gain	1.0000
11:61393883:G:C	acceptor_loss	1.0000
11:61393883:G:GG	acceptor_gain	1.0000
11:61393883:GGT:G	acceptor_gain	1.0000
11:61393975:TGG:T	donor_loss	1.0000
11:61393976:GGTA:G	donor_loss	1.0000
11:61393977:G:GG	donor_gain	1.0000
11:61393978:TAAGT:T	donor_loss	1.0000
11:61392665:GG:G	donor_loss	0.9900
11:61392667:T:G	donor_loss	0.9900
11:61393282:G:GA	donor_gain	0.9900
11:61393329:AAAGG:A	donor_loss	0.9900
11:61393330:AAGGT:A	donor_loss	0.9900
11:61393331:AGGT:A	donor_loss	0.9900
11:61393333:GTAA:G	donor_loss	0.9900
11:61393334:T:A	donor_loss	0.9900
11:61393882:AG:A	acceptor_gain	0.9900
11:61393883:GG:G	acceptor_gain	0.9900
11:61393883:GGTGT:G	acceptor_gain	0.9900
11:61393955:G:GT	donor_gain	0.9900
11:61393972:TTTTG:T	donor_gain	0.9900
11:61393973:TTTG:T	donor_gain	0.9900
11:61393975:TG:T	donor_gain	0.9900
11:61393976:GG:G	donor_gain	0.9900
11:61397893:G:GT	donor_gain	0.9900
11:61392677:G:GT	donor_gain	0.9800
11:61393225:TTTCA:T	acceptor_loss	0.9800

AlphaMissense

916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61393331:A:C	K45N	0.991
11:61393331:A:T	K45N	0.991
11:61397818:A:C	S92R	0.986
11:61397820:C:A	S92R	0.986
11:61397820:C:G	S92R	0.986
11:61393330:A:T	K45I	0.981
11:61397782:G:A	G80R	0.979
11:61397782:G:C	G80R	0.979
11:61397894:A:T	E117V	0.976
11:61397783:G:T	G80V	0.966
11:61397787:C:A	N81K	0.964
11:61397787:C:G	N81K	0.964
11:61393923:A:T	D59V	0.963
11:61397874:G:C	Q110H	0.963
11:61397874:G:T	Q110H	0.963
11:61397783:G:A	G80E	0.960
11:61393965:G:C	R73P	0.953
11:61393922:G:C	D59H	0.950
11:61393976:G:C	G77R	0.948
11:61393923:A:C	D59A	0.946
11:61393949:G:A	G68R	0.941
11:61393949:G:C	G68R	0.941
11:61397774:G:A	G77D	0.940
11:61393329:A:G	K45E	0.934
11:61397893:G:A	E117K	0.934
11:61393330:A:C	K45T	0.932
11:61393922:G:T	D59Y	0.929
11:61397894:A:C	E117A	0.920
11:61393922:G:A	D59N	0.919
11:61393923:A:G	D59G	0.918

dbSNP variants (sampled 300 via entrez): RS1000344014 (11:61396469 C>T), RS1000437454 (11:61396743 G>A), RS1000493681 (11:61391560 G>C), RS1000607042 (11:61399087 C>T), RS1001124035 (11:61398563 TCTC>T), RS1001374141 (11:61392755 A>G), RS1001491231 (11:61392511 A>C), RS1001837097 (11:61396054 G>T), RS1002971232 (11:61394569 A>G), RS1003245912 (11:61394123 C>T), RS1003501697 (11:61396729 G>A), RS1003952404 (11:61399346 A>C), RS1004385062 (11:61393564 A>G), RS1004422941 (11:61393395 T>C), RS1004611770 (11:61392495 CT>C)

Disease associations

OMIM: gene MIM:613277 | disease phenotypes: MIM:213300, MIM:608091, MIM:603194, MIM:620996

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 2	Strong	Autosomal recessive
ciliopathy	Strong	Autosomal recessive
Joubert syndrome with oculorenal defect	Supportive	Autosomal recessive
orofaciodigital syndrome type 6	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
ciliopathy	Definitive	AR

Mondo (14): Joubert syndrome (MONDO:0018772), Joubert syndrome 2 (MONDO:0011963), Meckel syndrome, type 2 (MONDO:0011296), Joubert syndrome 1 (MONDO:0008944), retinitis pigmentosa 98 (MONDO:0975840), congenital nervous system disorder (MONDO:0002320), inherited retinal dystrophy (MONDO:0019118), retinal disorder (MONDO:0005283), Joubert syndrome and related disorders (MONDO:0015369), microcephaly (MONDO:0001149), Joubert syndrome with oculorenal defect (MONDO:0009480), orofaciodigital syndrome type 6 (MONDO:0010176), Meckel syndrome (MONDO:0018921), ciliopathy (MONDO:0005308)

Orphanet (5): Isolated Joubert syndrome (Orphanet:475), Joubert syndrome with oculorenal defect (Orphanet:2318), Meckel syndrome (Orphanet:564), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Joubert syndrome and related disorders (Orphanet:140874)

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000037	Male pseudohermaphroditism
HP:0000050	Hypoplastic male external genitalia
HP:0000062	Ambiguous genitalia
HP:0000068	Urethral atresia
HP:0000073	Ureteral duplication
HP:0000083	Renal insufficiency
HP:0000090	Nephronophthisis
HP:0000104	Renal agenesis
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000175	Cleft palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000199	Tongue nodules
HP:0000218	High palate
HP:0000221	Furrowed tongue
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears

GWAS associations

0 associations (top):

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
C537430	Arima syndrome (supp.)
C536294	Joubert syndrome 2 (supp.)
C536131	Meckel syndrome type 2 (supp.)
C536531	Orofaciodigital syndrome 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Air Pollutants	increases abundance, affects expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Ozone	affects expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
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]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
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
NCT00068224	Not specified	COMPLETED	Clinical and Molecular Investigations Into Ciliopathies
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