TMEM231

Summary

TMEM231 (transmembrane protein 231, HGNC:37234) is a protein-coding gene on chromosome 16q23.1, encoding Transmembrane protein 231 (Q9H6L2). Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.

This gene encodes a transmembrane protein, which is a component of the B9 complex involved in the formation of the diffusion barrier between the cilia and plasma membrane. Mutations in this gene cause Joubert syndrome (JBTS). Multiple alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 79583 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 521 total — 32 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 123
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001077418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37234
Approved symbol	TMEM231
Name	transmembrane protein 231
Location	16q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22167, ALYE870, PRO1886, JBTS20, MKS11
Ensembl gene	ENSG00000205084
Ensembl biotype	protein_coding
OMIM	614949
Entrez	79583

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 12 protein_coding, 8 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000258173, ENST00000561809, ENST00000562410, ENST00000564318, ENST00000564576, ENST00000565067, ENST00000568377, ENST00000569294, ENST00000570006, ENST00000615437, ENST00000685935, ENST00000686547, ENST00000686680, ENST00000688195, ENST00000688270, ENST00000688618, ENST00000689040, ENST00000692097, ENST00000692215, ENST00000692689, ENST00000693457, ENST00000693682, ENST00000870301, ENST00000870302, ENST00000922029

RefSeq mRNA: 2 — MANE Select: NM_001077418 NM_001077416, NM_001077418

CCDS: CCDS45530

Canonical transcript exons

ENST00000258173 — 7 exons

Exon	Start	End
ENSE00002601415	75536741	75540174
ENSE00002614895	75556071	75556252
ENSE00003653188	75555804	75555973
ENSE00003705384	75545352	75545495
ENSE00003708021	75545826	75545954
ENSE00003708515	75542602	75542683
ENSE00003709458	75541350	75541455

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5994 / max 96.5163, expressed in 1640 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158178	9.5994	1640

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.33	gold quality
epithelium of bronchus	UBERON:0002031	99.07	gold quality
bronchus	UBERON:0002185	98.49	gold quality
right uterine tube	UBERON:0001302	98.31	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.21	gold quality
nasal cavity epithelium	UBERON:0005384	91.55	gold quality
epithelium of nasopharynx	UBERON:0001951	89.97	gold quality
oocyte	CL:0000023	89.61	gold quality
caput epididymis	UBERON:0004358	89.55	gold quality
secondary oocyte	CL:0000655	89.23	gold quality
ventricular zone	UBERON:0003053	89.08	gold quality
nasal cavity mucosa	UBERON:0001826	88.15	gold quality
choroid plexus epithelium	UBERON:0003911	87.71	gold quality
tibia	UBERON:0000979	87.10	gold quality
nucleus accumbens	UBERON:0001882	84.97	gold quality
adenohypophysis	UBERON:0002196	84.91	gold quality
caudate nucleus	UBERON:0001873	84.90	gold quality
endocervix	UBERON:0000458	84.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.42	gold quality
stromal cell of endometrium	CL:0002255	84.33	gold quality
pituitary gland	UBERON:0000007	84.24	gold quality
hypothalamus	UBERON:0001898	84.06	gold quality
left testis	UBERON:0004533	83.82	gold quality
right testis	UBERON:0004534	83.61	gold quality
prefrontal cortex	UBERON:0000451	83.25	gold quality
sperm	CL:0000019	83.10	gold quality
left uterine tube	UBERON:0001303	82.91	gold quality
right frontal lobe	UBERON:0002810	82.77	gold quality
testis	UBERON:0000473	82.49	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	62.03
E-ANND-3	yes	11.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting TMEM231, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4692	100.00	67.32	2066
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-3140-5P	99.39	69.04	1136

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 5)

• mutations in TMEM231 cause JBTS, reinforcing the relationship between this condition and the disruption of the barrier at the ciliary transition zone. (PMID:23012439)
• TMEM231 represents a novel MKS locus. The very recent identification of TMEM231 mutations in Joubert syndrome supports the growing appreciation of the overlap in the molecular pathogenesis between these two ciliopathies. (PMID:23349226)
• Tmem231 is critical for organizing the Meckel syndrome complex and controlling ciliary composition, defects in which cause OFD3 and MKS. (PMID:25869670)
• Results identified a rare gene conversion event in TMEM231, leading to loss of exon 4, which in combination with c.712G>A missense mutation caused Joubert syndrome and in combination with c.334T>G missense mutation caused Meckel-Gruber syndrome. (PMID:27449316)
• Long-read nanopore sequencing resolves a TMEM231 gene conversion event causing Meckel-Gruber syndrome. (PMID:31663672)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem231	ENSDARG00000042272
mus_musculus	Tmem231	ENSMUSG00000031951
rattus_norvegicus	Tmem231	ENSRNOG00000021517
drosophila_melanogaster	CG14020	FBGN0031707
caenorhabditis_elegans		WBGENE00020825

Protein

Protein identifiers

Transmembrane protein 231 — Q9H6L2 (reviewed: Q9H6L2)

All UniProt accessions (11): A0A087WW60, A0A8I5KU61, A0A8I5KUT8, A0A8I5KVD3, A0A8I5KVP2, A0A8I5KX99, A0A8I5QJQ3, Q9H6L2, H3BMW7, H3BPY4, H3BTN6

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling.

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

Subcellular location. Cell projection. Cilium membrane.

Disease relevance. Joubert syndrome 20 (JBTS20) [MIM:614970] 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 11 (MKS11) [MIM:615397] 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.

Similarity. Belongs to the TMEM231 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H6L2-1	1	yes
Q9H6L2-2	2
Q9H6L2-3	3

RefSeq proteins (2): NP_001070884, NP_001070886* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019306	TMEM231	Family

Pfam: PF10149

UniProt features (13 total): sequence variant 3, glycosylation site 3, transmembrane region 2, sequence conflict 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6L2-F1	88.65	0.67

Functional residue map

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

Glycosylation sites (3): 194, 199, 221

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 336 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_APPENDAGE_DEVELOPMENT, GOBP_ORGANELLE_ASSEMBLY, GOBP_COLUMNAR_CUBOIDAL_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_NEUROEPITHELIAL_CELL_DIFFERENTIATION, GOBP_EMBRYO_DEVELOPMENT, GOBP_SENSORY_ORGAN_DEVELOPMENT

GO Biological Process (9): in utero embryonic development (GO:0001701), vasculature development (GO:0001944), smoothened signaling pathway (GO:0007224), regulation of protein localization (GO:0032880), embryonic digit morphogenesis (GO:0042733), camera-type eye development (GO:0043010), cilium assembly (GO:0060271), neuroepithelial cell differentiation (GO:0060563), cell projection organization (GO:0030030)

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

GO Cellular Component (7): ciliary transition zone (GO:0035869), MKS complex (GO:0036038), ciliary membrane (GO:0060170), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium	2
chordate embryonic development	1
system development	1
circulatory system development	1
cell surface receptor signaling pathway	1
intracellular protein localization	1
regulation of localization	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
eye development	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
columnar/cuboidal epithelial cell differentiation	1
cellular component organization	1
binding	1
protein-containing complex	1
ciliary transition zone	1
cell projection membrane	1
bounding membrane of organelle	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM231	B9D1	Q9UPM9	978
TMEM231	TMEM67	Q5HYA8	973
TMEM231	TCTN1	Q2MV58	964
TMEM231	TCTN2	Q96GX1	955
TMEM231	TMEM216	Q9P0N5	955
TMEM231	CC2D2A	Q9P2K1	953
TMEM231	B9D2	Q9BPU9	943
TMEM231	CEP290	O15078	926
TMEM231	TMEM237	Q96Q45	924
TMEM231	MKS1	Q9NXB0	890
TMEM231	TMEM17	Q86X19	881
TMEM231	NPHP1	O15259	879
TMEM231	RPGRIP1L	Q68CZ1	879
TMEM231	TCTN3	Q6NUS6	879
TMEM231	AHI1	Q8N157	863

IntAct

51 interactions, top by confidence:

A	B	Type	Score
TCTN2	CLGN	psi-mi:“MI:0914”(association)	0.780
B9D2	TMEM231	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TMEM231	TCTN1	psi-mi:“MI:0914”(association)	0.640
TCTN2	TCTN3	psi-mi:“MI:0914”(association)	0.640
TMEM231	KRT31	psi-mi:“MI:0915”(physical association)	0.560
TMEM231	KRT40	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	TMEM231	psi-mi:“MI:0915”(physical association)	0.560
KRT40	TMEM231	psi-mi:“MI:0915”(physical association)	0.560
TMEM231	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
KRT31	TMEM231	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TMEM107	TMEM231	psi-mi:“MI:0915”(physical association)	0.400
TMEM218	TMEM231	psi-mi:“MI:0915”(physical association)	0.400
TMEM231	GPR37	psi-mi:“MI:0915”(physical association)	0.370
UPK1A	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA3	TMEM223	psi-mi:“MI:0914”(association)	0.350
HTR3C	TMEM223	psi-mi:“MI:0914”(association)	0.350
BTNL8	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ASIC4	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SYNE4	GOLIM4	psi-mi:“MI:0914”(association)	0.350
TMEM231	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
NCEH1	C1QL1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (125): TMEM231 (Two-hybrid), KRT40 (Two-hybrid), NOTCH2NL (Two-hybrid), NDFIP2 (Affinity Capture-MS), LSR (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), ATP2C1 (Affinity Capture-MS), RAB9A (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), PLEKHB2 (Affinity Capture-MS), B9D1 (Affinity Capture-MS), RNF149 (Affinity Capture-MS)

ESM2 similar proteins: A1L134, A4D1U4, A6NFY4, A7MB75, D3Z291, F1NNL1, O43292, O95870, P51571, P70295, Q0PGW2, Q0VF94, Q17RQ9, Q1JPD2, Q28DH9, Q2HJ63, Q2TBX5, Q3U128, Q3U284, Q3UHG7, Q3UX43, Q4R8P0, Q5FVM1, Q5HYA8, Q5NDE9, Q5NDF0, Q5NDF2, Q5R6S0, Q5RBT8, Q5REH6, Q5RJQ8, Q6DDX8, Q6MG55, Q8BJQ9, Q8BXQ2, Q8C1F4, Q8IU99, Q8J025, Q8TDX6, Q8VEC4

Diamond homologs: A7MB75, F1NNL1, F7B645, Q3U284, Q5FVM1, Q5RBT8, Q7T316, Q9H6L2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Anchoring of the basal body to the plasma membrane	6	21.2×	2e-05
Cilium Assembly	6	20.4×	2e-05
Organelle biogenesis and maintenance	6	12.4×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
cilium assembly	7	13.6×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	16
Uncertain significance	234
Likely benign	160
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1252091	NM_001077418.3(TMEM231):c.316G>A (p.Glu106Lys)	Pathogenic
1323693	NM_001077418.3(TMEM231):c.668_669del (p.Thr223fs)	Pathogenic
1351746	NC_000016.9:g.(?75573892)(75690509_?)del	Pathogenic
1368287	NM_001077418.3(TMEM231):c.139+1del	Pathogenic
1388711	NM_001077418.3(TMEM231):c.583-1_583delinsAG	Pathogenic
1398946	NM_001077418.3(TMEM231):c.354dup (p.His119fs)	Pathogenic
1418103	NC_000016.9:g.(?75573892)(75575373_?)del	Pathogenic
1430979	NM_001077418.3(TMEM231):c.4G>A (p.Ala2Thr)	Pathogenic
1448559	NM_001077418.3(TMEM231):c.535C>T (p.Gln179Ter)	Pathogenic
1457752	NC_000016.9:g.(?75490611)(75576599_?)del	Pathogenic
1458388	NM_001077418.3(TMEM231):c.124G>A (p.Ala42Thr)	Pathogenic
1459430	NC_000016.9:g.(?75573892)(75579413_?)del	Pathogenic
1802034	NM_001077418.3(TMEM231):c.544C>T (p.Gln182Ter)	Pathogenic
1960880	NM_001077418.3(TMEM231):c.583-1_593delinsAGTATCTGTGAC	Pathogenic
2054331	NM_001077418.3(TMEM231):c.-37G>A	Pathogenic
2423617	NC_000016.9:g.(?75589682)(75590169_?)del	Pathogenic
2921947	NM_001077418.3(TMEM231):c.3_4insAGCTCTATGAGCTCATG (p.Ala2fs)	Pathogenic
2934525	NM_001077418.3(TMEM231):c.140-9_140-8del	Pathogenic
2941997	NM_001077418.3(TMEM231):c.33C>A (p.Val11=)	Pathogenic
3068925	NM_001077418.3(TMEM231):c.538C>T (p.Gln180Ter)	Pathogenic
3243522	NC_000016.9:g.(?75579704)(75579872_?)del	Pathogenic
3375765	NM_001077418.3(TMEM231):c.770+1A>G	Pathogenic
3749689	NM_001077418.3(TMEM231):c.164_176dup (p.Thr60fs)	Pathogenic
3756171	NM_001077418.3(TMEM231):c.379C>T (p.Gln127Ter)	Pathogenic
3757816	NM_001077418.3(TMEM231):c.208del (p.Val70fs)	Pathogenic
437010	NM_001077418.3(TMEM231):c.438+1G>A	Pathogenic
4688201	NM_001077418.3(TMEM231):c.505del (p.Gln169fs)	Pathogenic
473319	NC_000016.10:g.(?75539974)(75545515_?)del	Pathogenic
4786495	NM_001077418.3(TMEM231):c.513C>A (p.Tyr171Ter)	Pathogenic
4790110	NM_001077418.3(TMEM231):c.308C>A (p.Ser103Ter)	Pathogenic

SpliceAI

1419 predictions. Top by Δscore:

Variant	Effect	Δscore
16:75540546:T:TA	donor_gain	1.0000
16:75542681:TAT:T	acceptor_gain	1.0000
16:75542681:TATC:T	acceptor_loss	1.0000
16:75542683:TCTGG:T	acceptor_loss	1.0000
16:75542684:CT:C	acceptor_loss	1.0000
16:75542685:T:A	acceptor_loss	1.0000
16:75542690:C:CT	acceptor_gain	1.0000
16:75545350:A:AC	donor_gain	1.0000
16:75545351:C:CC	donor_gain	1.0000
16:75545351:CG:C	donor_gain	1.0000
16:75556065:GCTCA:G	donor_loss	1.0000
16:75556066:CTCA:C	donor_loss	1.0000
16:75556067:TCACC:T	donor_loss	1.0000
16:75556068:CA:C	donor_loss	1.0000
16:75556069:A:AC	donor_gain	1.0000
16:75556069:A:AG	donor_loss	1.0000
16:75556070:C:CC	donor_gain	1.0000
16:75556070:C:CT	donor_loss	1.0000
16:75541359:T:TA	donor_gain	0.9900
16:75542680:ATATC:A	acceptor_loss	0.9900
16:75542682:ATC:A	acceptor_loss	0.9900
16:75542683:TC:T	acceptor_loss	0.9900
16:75542684:C:A	acceptor_loss	0.9900
16:75542684:C:CC	acceptor_gain	0.9900
16:75542692:C:CT	acceptor_gain	0.9900
16:75542693:G:T	acceptor_gain	0.9900
16:75542775:AGCAC:A	donor_gain	0.9900
16:75542779:C:CA	donor_gain	0.9900
16:75542800:A:AC	donor_gain	0.9900
16:75542801:C:CC	donor_gain	0.9900

AlphaMissense

2053 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:75540120:G:C	S275R	0.996
16:75540120:G:T	S275R	0.996
16:75540122:T:G	S275R	0.996
16:75540137:A:G	W270R	0.995
16:75540137:A:T	W270R	0.995
16:75545469:G:C	S155R	0.995
16:75545469:G:T	S155R	0.995
16:75545471:T:G	S155R	0.995
16:75555861:G:C	S84R	0.994
16:75555861:G:T	S84R	0.994
16:75555863:T:G	S84R	0.994
16:75540139:G:T	A269D	0.989
16:75545854:A:G	L137P	0.987
16:75545407:A:G	L176P	0.986
16:75555862:C:A	S84I	0.985
16:75555866:A:G	W83R	0.982
16:75555866:A:T	W83R	0.982
16:75555924:G:C	F63L	0.979
16:75555924:G:T	F63L	0.979
16:75555926:A:G	F63L	0.979
16:75540144:C:A	K267N	0.976
16:75540144:C:G	K267N	0.976
16:75541374:A:T	I249N	0.976
16:75540128:A:G	Y273H	0.975
16:75540128:A:C	Y273D	0.973
16:75556097:G:C	P38R	0.973
16:75556097:G:T	P38Q	0.973
16:75556085:G:T	A42D	0.970
16:75545848:A:G	L139P	0.968
16:75540073:A:T	V291E	0.967

dbSNP variants (sampled 300 via entrez): RS1000171910 (16:75546657 G>C), RS1000280536 (16:75541710 A>C,T), RS1000354445 (16:75551027 T>C), RS1000406430 (16:75550684 G>C), RS1000442477 (16:75545814 G>A), RS1000562089 (16:75541186 T>TC), RS1000788913 (16:75550905 C>A,T), RS1000873902 (16:75546073 C>A,T), RS1001176142 (16:75545275 T>A), RS1001210330 (16:75545102 C>A,T), RS1001314750 (16:75540294 C>A), RS1001395024 (16:75549960 C>A), RS1001598678 (16:75553640 G>A), RS1001668064 (16:75546593 C>A,G), RS1001764180 (16:75550148 C>T)

Disease associations

OMIM: gene MIM:614949 | disease phenotypes: MIM:614970, MIM:615397, MIM:213300, MIM:610805, MIM:249000, MIM:258850

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 20	Definitive	Autosomal recessive
Meckel syndrome, type 11	Strong	Autosomal recessive
Joubert syndrome with oculorenal defect	Supportive	Autosomal recessive
orofaciodigital syndrome III	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 (9): Joubert syndrome 20 (MONDO:0013994), Meckel syndrome, type 11 (MONDO:0014164), Joubert syndrome and related disorders (MONDO:0015369), ciliopathy (MONDO:0005308), Joubert syndrome (MONDO:0018772), congenital anomaly of kidney and urinary tract (MONDO:0019719), Meckel syndrome (MONDO:0018921), orofaciodigital syndrome III (MONDO:0009793), Joubert syndrome with oculorenal defect (MONDO:0009480)

Orphanet (6): Isolated Joubert syndrome (Orphanet:475), Meckel syndrome (Orphanet:564), Joubert syndrome and related disorders (Orphanet:140874), Ciliopathy (Orphanet:363250), Renal or urinary tract malformation (Orphanet:93545), Orofaciodigital syndrome type 3 (Orphanet:2752)

HPO phenotypes

123 total (30 of 123 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:0000104	Renal agenesis
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000113	Polycystic kidney dysplasia
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: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
HP:0000405	Conductive hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002553_10	Pancreatic cancer	1.000000e-10
GCST004962_3	Diarrhoea in darapladib-treated cardiovascular disease (time to event)	2.000000e-09
GCST006190_3	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	7.000000e-08
GCST006192_51	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-12
GCST006192_74	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-18
GCST006193_36	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-07
GCST006195_18	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-12
GCST006195_68	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-18
GCST006195_80	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008395	response to darapladib
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C537430	Arima syndrome (supp.)
C566906	Cakut (supp.)
C557817	Orofaciodigital syndrome 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, decreases expression	3
Cyclosporine	increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
pentanal	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression	1
Niclosamide	increases expression	1
Smoke	increases abundance, increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	affects expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
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)
NCT04537364	Not specified	COMPLETED	Prediction of Renal Parenchymal Damage of CAKUT
NCT06921733	Not specified	RECRUITING	Ultrasound Localization Microscopy in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)