KIAA0753

Summary

KIAA0753 (HGNC:29110) is a protein-coding gene on chromosome 17p13.1, encoding Protein moonraker (Q2KHM9). Involved in centriole duplication.

This gene encodes a subunit of a protein complex that regulates ciliogenesis and cilia maintenance. The encoded protein has also been shown to regulate centriolar duplication. Mutations in this gene cause an orofaciodigital syndrome and a form of Joubert syndrome in human patients.

Source: NCBI Gene 9851 — RefSeq curated summary.

At a glance

• Gene–disease (curated): orofaciodigital syndrome XV (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 575 total — 27 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 132
• MANE Select transcript: NM_014804

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29110
Approved symbol	KIAA0753
Name	KIAA0753
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	OFIP, MNR
Ensembl gene	ENSG00000198920
Ensembl biotype	protein_coding
OMIM	617112
Entrez	9851

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000361413, ENST00000542826, ENST00000570455, ENST00000570790, ENST00000571642, ENST00000572235, ENST00000572370, ENST00000575027, ENST00000576281, ENST00000576823

RefSeq mRNA: 2 — MANE Select: NM_014804 NM_001351225, NM_014804

CCDS: CCDS42247, CCDS86564

Canonical transcript exons

ENST00000361413 — 19 exons

Exon	Start	End
ENSE00000679688	6635011	6635171
ENSE00001312791	6578147	6579864
ENSE00002675301	6640637	6640711
ENSE00003470777	6611919	6612148
ENSE00003527318	6607181	6607270
ENSE00003527484	6589779	6590003
ENSE00003528833	6622882	6623097
ENSE00003536795	6594972	6595053
ENSE00003560395	6620788	6620998
ENSE00003575534	6628117	6628741
ENSE00003585688	6609994	6610160
ENSE00003587794	6590510	6590630
ENSE00003589739	6600380	6600458
ENSE00003615054	6606873	6606962
ENSE00003626300	6608348	6608464
ENSE00003627128	6596158	6596343
ENSE00003655527	6623509	6623571
ENSE00003670756	6599237	6599320
ENSE00003678931	6624755	6624861

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 90.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2134 / max 111.2332, expressed in 1707 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164057	6.7273	1696
164058	0.4707	273
164056	0.0153	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	90.18	gold quality
lower esophagus	UBERON:0013473	88.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.01	gold quality
lateral globus pallidus	UBERON:0002476	87.59	silver quality
ventricular zone	UBERON:0003053	87.19	gold quality
olfactory bulb	UBERON:0002264	87.03	gold quality
right testis	UBERON:0004534	86.87	gold quality
secondary oocyte	CL:0000655	86.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.74	gold quality
left testis	UBERON:0004533	86.73	gold quality
epithelium of bronchus	UBERON:0002031	86.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.50	gold quality
type B pancreatic cell	CL:0000169	86.42	gold quality
bronchus	UBERON:0002185	86.33	gold quality
male germ cell	CL:0000015	86.07	silver quality
oocyte	CL:0000023	86.07	gold quality
mucosa of urinary bladder	UBERON:0001259	85.95	gold quality
right uterine tube	UBERON:0001302	85.90	gold quality
cardia of stomach	UBERON:0001162	85.89	gold quality
testis	UBERON:0000473	85.87	gold quality
sperm	CL:0000019	85.79	silver quality
bronchial epithelial cell	CL:0002328	85.72	gold quality
germinal epithelium of ovary	UBERON:0001304	85.62	gold quality
smooth muscle tissue	UBERON:0001135	85.52	gold quality
saphenous vein	UBERON:0007318	85.47	gold quality
epithelium of nasopharynx	UBERON:0001951	85.37	gold quality
calcaneal tendon	UBERON:0003701	85.15	gold quality
embryo	UBERON:0000922	84.94	gold quality
ganglionic eminence	UBERON:0004023	84.60	gold quality
adrenal tissue	UBERON:0018303	84.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting KIAA0753, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4680-3P	98.64	68.60	2093

Literature-anchored findings (GeneRIF, showing 5)

• Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C). The intronic mutation alters normal splicing by activating a cryptic acceptor splice site in exon 16 (PMID:28220259)
• We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. (PMID:29138412)
• A ciliopathy complex builds distal appendages to initiate ciliogenesis. (PMID:34241634)
• Genetic and phenotypic heterogeneity in KIAA0753-related ciliopathies. (PMID:34523780)
• CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum. (PMID:34711653)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-243i1.1	ENSDARG00000034227
mus_musculus	4933427D14Rik	ENSMUSG00000020807
rattus_norvegicus	4933427D14Rikl	ENSRNOG00000014027

Protein

Protein identifiers

Protein moonraker — Q2KHM9 (reviewed: Q2KHM9)

Alternative names: OFD1- and FOPNL-interacting protein

All UniProt accessions (6): Q2KHM9, F6SFD5, I3L1P2, I3L2A7, I3L341, I3L3Y0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in centriole duplication. Positively regulates CEP63 centrosomal localization. Required for WDR62 centrosomal localization and promotes the centrosomal localization of CDK2. May play a role in cilium assembly.

Subunit / interactions. Interacts with CEP63. Interacts with WDR62. Forms a complex with OFD1 and CEP20/FOR20. Interacts with PCM1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Centriolar satellite.

Disease relevance. Orofaciodigital syndrome 15 (OFD15) [MIM:617127] A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD15 features include facial dysmorphism, lobulated tongue, clefting of the alveolar ridges, left hand postaxial polydactyly, broad right hallux and left hallux duplication, and intermittent respiratory difficulty. Brain anomalies include vermis hypoplasia with molar tooth sign, agenesis of corpus callosum, and ventricular dilation. OFD15 inheritance is autosomal recessive. The disease may be caused by variants affecting the gene represented in this entry. Joubert syndrome 38 (JBTS38) [MIM:619476] A form of Joubert syndrome, 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, renal disease, liver fibrosis, and polydactyly. JBTS38 inheritance is autosomal recessive. The disease may be caused by variants affecting the gene represented in this entry. Short-rib thoracic dysplasia 21 without polydactyly (SRTD21) [MIM:619479] A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a ’trident’ appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q2KHM9-1	1	yes
Q2KHM9-2	2

RefSeq proteins (2): NP_001338154, NP_055619* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031447	MNR	Family

Pfam: PF15718

UniProt features (29 total): sequence variant 12, region of interest 5, modified residue 4, compositionally biased region 3, sequence conflict 2, chain 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2KHM9-F1	59.08	0.10

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 (4): 287, 409, 700, 826

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 373 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOCC_MICROTUBULE_ORGANIZING_CENTER, TERAMOTO_OPN_TARGETS_CLUSTER_8, GOBP_CENTRIOLE_ASSEMBLY, GOBP_CILIUM_ORGANIZATION, MODULE_171, MODULE_301, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELL_PROJECTION_ORGANIZATION, MODULE_188, GOBP_CENTROSOME_DUPLICATION, GOCC_CENTRIOLE, GOBP_CELL_CYCLE_PROCESS

GO Biological Process (4): centriole replication (GO:0007099), cilium assembly (GO:0060271), cytosolic ciliogenesis (GO:0061824), protein localization to centrosome (GO:0071539)

GO Molecular Function (4): metal ion binding (GO:0046872), 2 iron, 2 sulfur cluster binding (GO:0051537), protein binding (GO:0005515), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (10): endoplasmic reticulum (GO:0005783), centrosome (GO:0005813), centriole (GO:0005814), microtubule organizing center (GO:0005815), cytosol (GO:0005829), cilium (GO:0005929), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
microtubule organizing center	3
cytoplasm	2
intracellular membraneless organelle	2
cell cycle process	1
centrosome duplication	1
centriole assembly	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
cilium assembly	1
protein localization to microtubule organizing center	1
cation binding	1
iron-sulfur cluster binding	1
binding	1
metal cluster binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule cytoskeleton	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
centrosome	1
cilium	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIAA0753	CCDC14	Q49A88	807
KIAA0753	CEP63	Q96MT8	789
KIAA0753	OFD1	O75665	762
KIAA0753	CEP20	Q96NB1	737
KIAA0753	CEP120	Q8N960	624
KIAA0753	LHB	P01229	603
KIAA0753	CEP131	Q9UPN4	594
KIAA0753	TPH2	Q8IWU9	580
KIAA0753	CEP162	Q5TB80	557
KIAA0753	CNTLN	Q9NXG0	557
KIAA0753	RPGRIP1L	Q68CZ1	542
KIAA0753	AHI1	Q8N157	531
KIAA0753	CCDC18	Q5T9S5	521
KIAA0753	PIBF1	Q8WXW3	514
KIAA0753	CCDC13	Q8IYE1	505

IntAct

151 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
CSNK1E	PER1	psi-mi:“MI:0914”(association)	0.840
CEP20	OFD1	psi-mi:“MI:0914”(association)	0.710
KIAA0753	TCHP	psi-mi:“MI:0915”(physical association)	0.660
PCM1	KIAA0753	psi-mi:“MI:0915”(physical association)	0.650
PCM1	KIAA0753	psi-mi:“MI:0914”(association)	0.650
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
TEAD4	KIAA0753	psi-mi:“MI:0915”(physical association)	0.560
FAM161A	KIAA0753	psi-mi:“MI:0915”(physical association)	0.560
USHBP1	KIAA0753	psi-mi:“MI:0915”(physical association)	0.560
KIAA0753	ZNF114	psi-mi:“MI:0915”(physical association)	0.560
KIAA0753	CT55	psi-mi:“MI:0915”(physical association)	0.560
KIAA0753	GCC1	psi-mi:“MI:0915”(physical association)	0.560
KIAA0753	TEAD4	psi-mi:“MI:0915”(physical association)	0.560
KIAA0753	FAM161A	psi-mi:“MI:0915”(physical association)	0.560
KIAA0753	USHBP1	psi-mi:“MI:0915”(physical association)	0.560
GCC1	KIAA0753	psi-mi:“MI:0915”(physical association)	0.560
ZNF114	KIAA0753	psi-mi:“MI:0915”(physical association)	0.560
HGS	KIAA0753	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (227): KIAA0753 (Two-hybrid), CT55 (Two-hybrid), GCC1 (Two-hybrid), USHBP1 (Two-hybrid), FAM161A (Two-hybrid), ZNF114 (Two-hybrid), KIAA0753 (Proximity Label-MS), KIAA0753 (Proximity Label-MS), STIP1 (Proximity Label-MS), MAP7D3 (Proximity Label-MS), CDK1 (Proximity Label-MS), CEP55 (Proximity Label-MS), PIBF1 (Proximity Label-MS), OFD1 (Proximity Label-MS), CKAP2 (Proximity Label-MS)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0JMF7, A2AHC3, A2AIW0, A5D8S0, A5WUN7, A8PUI7, B0BM16, B1H1S4, B2GUZ2, B7ZS37, D3IUT5, D3Z8E6, D4AEC2, F1QB81, F1R983, P53995, Q08AD1, Q0VF22, Q13129, Q16533, Q2KHM9, Q2T9I9, Q49A88, Q4R815, Q58EL7, Q5CZC0, Q5RHB5, Q5T5Y3, Q66H35, Q6DJL7, Q6DRL4, Q6IRN6, Q6PUR7, Q7L2Z9, Q7Z4H7, Q8C263, Q8CGZ2, Q8CJ27

Diamond homologs: Q2KHM9, Q6A000

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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
Loss of Nlp from mitotic centrosomes	14	39.0×	3e-17
Loss of proteins required for interphase microtubule organization from the centrosome	14	39.0×	3e-17
AURKA Activation by TPX2	14	37.4×	5e-17
Anchoring of the basal body to the plasma membrane	17	33.7×	1e-19
Recruitment of mitotic centrosome proteins and complexes	14	33.4×	2e-16
Regulation of PLK1 Activity at G2/M Transition	14	31.2×	5e-16
Recruitment of NuMA to mitotic centrosomes	14	28.6×	1e-15
Centrosome maturation	6	26.7×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	6	53.0×	3e-07
non-motile cilium assembly	5	17.5×	1e-03
cilium assembly	12	10.6×	3e-07
intracellular protein localization	6	7.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	13
Uncertain significance	253
Likely benign	175
Benign	59

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1195877	NM_014804.3(KIAA0753):c.769A>G (p.Arg257Gly)	Pathogenic
1195878	NM_014804.3(KIAA0753):c.2359-1G>C	Pathogenic
1196005	NM_014804.3(KIAA0753):c.1830-2A>G	Pathogenic
1350675	NM_014804.3(KIAA0753):c.2413C>T (p.Arg805Ter)	Pathogenic
1920610	NM_014804.3(KIAA0753):c.379C>T (p.Gln127Ter)	Pathogenic
2021463	NM_014804.3(KIAA0753):c.1941_1944del (p.Glu647fs)	Pathogenic
254661	NM_014804.3(KIAA0753):c.1891A>T (p.Lys631Ter)	Pathogenic
2694119	NM_014804.3(KIAA0753):c.1657del (p.Arg553fs)	Pathogenic
2806335	NM_014804.3(KIAA0753):c.2T>C (p.Met1Thr)	Pathogenic
2808953	NM_014804.3(KIAA0753):c.446C>G (p.Ser149Ter)	Pathogenic
2864585	NM_014804.3(KIAA0753):c.1700_1701del (p.Ala567fs)	Pathogenic
2873276	NM_014804.3(KIAA0753):c.350_351del (p.Ile117fs)	Pathogenic
2877164	NM_014804.3(KIAA0753):c.2002C>T (p.Gln668Ter)	Pathogenic
3607571	NM_014804.3(KIAA0753):c.148C>T (p.Arg50Ter)	Pathogenic
3642682	NM_014804.3(KIAA0753):c.1109T>A (p.Leu370Ter)	Pathogenic
3673752	NM_014804.3(KIAA0753):c.556_557insAA (p.Thr186fs)	Pathogenic
3689347	NM_014804.3(KIAA0753):c.210C>G (p.Tyr70Ter)	Pathogenic
3691629	NM_014804.3(KIAA0753):c.1226C>G (p.Ser409Ter)	Pathogenic
428614	NM_014804.3(KIAA0753):c.1271del (p.Pro424fs)	Pathogenic
428615	NM_014804.3(KIAA0753):c.943C>T (p.Gln315Ter)	Pathogenic
439846	NM_014804.3(KIAA0753):c.1571_1572del (p.Arg524fs)	Pathogenic
4693889	NM_014804.3(KIAA0753):c.2483dup (p.His828fs)	Pathogenic
4769159	NM_014804.3(KIAA0753):c.2147_2148del (p.Thr716fs)	Pathogenic
4770211	NM_014804.3(KIAA0753):c.205_206dup (p.Tyr70fs)	Pathogenic
4779251	NM_014804.3(KIAA0753):c.320_321del (p.Asp107fs)	Pathogenic
4809525	NM_014804.3(KIAA0753):c.832G>T (p.Glu278Ter)	Pathogenic
598087	NM_014804.3(KIAA0753):c.1323T>A (p.Tyr441Ter)	Pathogenic
1349501	NM_014804.3(KIAA0753):c.1315+1G>T	Likely pathogenic
1468622	NM_014804.3(KIAA0753):c.1104+1G>A	Likely pathogenic
1910257	NM_014804.3(KIAA0753):c.2173-2A>G	Likely pathogenic

SpliceAI

3755 predictions. Top by Δscore:

Variant	Effect	Δscore
17:6589775:TGAC:T	donor_loss	1.0000
17:6589776:GACCT:G	donor_loss	1.0000
17:6589777:ACC:A	donor_loss	1.0000
17:6589778:C:T	donor_loss	1.0000
17:6590004:C:CC	acceptor_gain	1.0000
17:6590508:A:AC	donor_gain	1.0000
17:6590509:C:CC	donor_gain	1.0000
17:6594967:CTCA:C	donor_loss	1.0000
17:6594968:TCA:T	donor_loss	1.0000
17:6594969:CA:C	donor_loss	1.0000
17:6594970:A:AC	donor_gain	1.0000
17:6594970:A:AT	donor_loss	1.0000
17:6594970:AC:A	donor_gain	1.0000
17:6594971:C:CG	donor_gain	1.0000
17:6594971:CC:C	donor_gain	1.0000
17:6594971:CCA:C	donor_gain	1.0000
17:6594971:CCAT:C	donor_gain	1.0000
17:6594971:CCATT:C	donor_gain	1.0000
17:6594983:T:TA	donor_gain	1.0000
17:6595049:TATTT:T	acceptor_gain	1.0000
17:6595050:ATTT:A	acceptor_gain	1.0000
17:6595051:TTT:T	acceptor_gain	1.0000
17:6595051:TTTC:T	acceptor_loss	1.0000
17:6595052:TT:T	acceptor_gain	1.0000
17:6595054:C:CC	acceptor_gain	1.0000
17:6595055:T:C	acceptor_gain	1.0000
17:6595055:T:TC	acceptor_gain	1.0000
17:6595056:T:C	acceptor_gain	1.0000
17:6595056:T:TC	acceptor_gain	1.0000
17:6596156:A:AC	donor_gain	1.0000

AlphaMissense

6368 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:6579765:G:C	F962L	0.993
17:6579765:G:T	F962L	0.993
17:6579767:A:G	F962L	0.993
17:6579766:A:G	F962S	0.988
17:6579777:G:C	F958L	0.988
17:6579777:G:T	F958L	0.988
17:6579779:A:G	F958L	0.988
17:6579785:C:G	A956P	0.988
17:6622958:A:G	L343P	0.985
17:6579814:A:G	L946P	0.983
17:6628727:A:C	F36L	0.981
17:6628727:A:T	F36L	0.981
17:6628729:A:G	F36L	0.981
17:6579791:C:G	A954P	0.979
17:6579778:A:G	F958S	0.976
17:6579766:A:C	F962C	0.973
17:6622970:A:G	L339P	0.972
17:6628158:A:G	L226P	0.969
17:6623063:C:G	R308P	0.968
17:6622964:C:G	R341P	0.965
17:6628728:A:G	F36S	0.963
17:6628524:G:T	A104D	0.962
17:6623058:C:G	A310P	0.961
17:6628537:C:G	A100P	0.961
17:6623070:C:G	A306P	0.960
17:6628525:C:G	A104P	0.958
17:6600405:A:G	L688S	0.957
17:6579839:C:G	A938P	0.956
17:6579850:A:G	L934P	0.954
17:6623069:G:T	A306D	0.954

dbSNP variants (sampled 300 via entrez): RS1000011721 (17:6620096 A>G), RS1000022662 (17:6578323 C>T), RS1000100195 (17:6577707 G>C), RS1000121297 (17:6614374 T>C), RS1000154413 (17:6626265 T>A), RS1000198234 (17:6631875 C>T), RS1000289177 (17:6583811 A>C), RS1000303932 (17:6601900 G>A), RS1000354180 (17:6638300 G>A), RS1000358524 (17:6595567 G>A), RS1000444143 (17:6607732 C>T), RS1000459598 (17:6615547 G>A), RS1000550813 (17:6615324 G>A,C), RS1000788226 (17:6639355 G>A,C), RS1000794006 (17:6607965 T>A)

Disease associations

OMIM: gene MIM:617112 | disease phenotypes: MIM:617127, MIM:619476, MIM:619479, MIM:208500, MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
orofaciodigital syndrome XV	Strong	Autosomal recessive
short-rib thoracic dysplasia 21 without polydactyly	Strong	Autosomal recessive
orofaciodigital syndrome type 6	Supportive	Autosomal recessive
Jeune syndrome	Supportive	Autosomal recessive

Mondo (6): orofaciodigital syndrome XV (MONDO:0014932), Joubert syndrome 38 (MONDO:0030353), short-rib thoracic dysplasia 21 without polydactyly (MONDO:0030356), Jeune syndrome (MONDO:0018770), Joubert syndrome (MONDO:0018772), orofaciodigital syndrome type 6 (MONDO:0010176)

Orphanet (2): Jeune syndrome (Orphanet:474), Isolated Joubert syndrome (Orphanet:475)

HPO phenotypes

132 total (30 of 132 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000083	Renal insufficiency
HP:0000090	Nephronophthisis
HP:0000104	Renal agenesis
HP:0000112	Nephropathy
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000199	Tongue nodules
HP:0000200	Short lingual frenulum
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000508	Ptosis

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004278_7	Pulse pressure	2.000000e-14
GCST006086_16	Familial lung cancer	7.000000e-06
GCST007096_3	Pulse pressure	2.000000e-17
GCST007099_148	Systolic blood pressure	1.000000e-07
GCST007267_234	Systolic blood pressure	7.000000e-11
GCST007269_301	Pulse pressure	2.000000e-25
GCST009617_2	LDL cholesterol levels x thiazide or thiazide-like diuretics use interaction	1.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0006953	family history of lung cancer
EFO:0006335	systolic blood pressure
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C537571	Jeune syndrome (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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression, affects expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	affects cotreatment, decreases methylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Antimycin A	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Caffeine	increases phosphorylation	1
Gallic Acid	decreases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases expression	1
Genistein	increases expression, increases reaction	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00948376	Not specified	COMPLETED	Natural History of Asphyxiating Thoracic Dystrophy (DTJ)
NCT04143841	Not specified	TERMINATED	Viveye Ocular Magnetic Neurostimulation System (OMNS) for the Management of Severe Dry Eye Disease
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study