RIC1

Summary

RIC1 (RIC1 partner of RAB6A GEF complex, HGNC:17686) is a protein-coding gene on chromosome 9p24.1, encoding Guanine nucleotide exchange factor subunit RIC1 (Q4ADV7). The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP, and may thereby be required for efficient fusion of endosome-derived vesicles with the Golgi compartment. It is a selective cancer dependency (DepMap: 56.9% of cell lines).

Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in several processes, including positive regulation of GTPase activity; regulation of extracellular matrix constituent secretion; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex.

Source: NCBI Gene 57589 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cleft lip/palate (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 228 total — 1 pathogenic
• Phenotypes (HPO): 43
• Cancer dependency (DepMap): dependent in 56.9% of screened cell lines
• MANE Select transcript: NM_020829

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17686
Approved symbol	RIC1
Name	RIC1 partner of RAB6A GEF complex
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	bA207C16.1
Ensembl gene	ENSG00000107036
Ensembl biotype	protein_coding
OMIM	610354
Entrez	57589

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000251879, ENST00000276898, ENST00000414202, ENST00000418622, ENST00000490816, ENST00000545243, ENST00000545641, ENST00000894134, ENST00000894135, ENST00000928612, ENST00000928613

RefSeq mRNA: 3 — MANE Select: NM_020829 NM_001135920, NM_001206557, NM_020829

CCDS: CCDS34982, CCDS47949, CCDS75811

Canonical transcript exons

ENST00000414202 — 26 exons

Exon	Start	End
ENSE00000506771	5753536	5753646
ENSE00000813161	5689959	5690038
ENSE00000813162	5713896	5714003
ENSE00000813170	5753200	5753238
ENSE00000982124	5773958	5776557
ENSE00003474454	5765662	5765798
ENSE00003475552	5756212	5756372
ENSE00003475626	5742869	5743013
ENSE00003493432	5762541	5762660
ENSE00003516082	5743689	5743737
ENSE00003529156	5770087	5770278
ENSE00003536373	5772892	5773080
ENSE00003538306	5754841	5754930
ENSE00003547567	5765414	5765572
ENSE00003565226	5738450	5738538
ENSE00003577401	5720614	5720750
ENSE00003582284	5732388	5732479
ENSE00003606844	5763140	5763868
ENSE00003619824	5772564	5772741
ENSE00003619855	5757313	5757451
ENSE00003635289	5747302	5747505
ENSE00003645094	5720182	5720324
ENSE00003663704	5768970	5769256
ENSE00003673668	5745931	5746083
ENSE00003737782	5656583	5656690
ENSE00003841574	5629107	5629453

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 91.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.7063 / max 330.0133, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95962	26.4238	1816
95961	0.8493	451
95960	0.4332	238

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	91.93	silver quality
bone marrow cell	CL:0002092	90.04	gold quality
monocyte	CL:0000576	89.82	gold quality
adrenal tissue	UBERON:0018303	89.59	gold quality
leukocyte	CL:0000738	89.38	gold quality
upper arm skin	UBERON:0004263	89.23	gold quality
epithelial cell of pancreas	CL:0000083	88.75	gold quality
sperm	CL:0000019	88.41	gold quality
stromal cell of endometrium	CL:0002255	88.25	gold quality
calcaneal tendon	UBERON:0003701	87.56	gold quality
gastrocnemius	UBERON:0001388	87.28	gold quality
deltoid	UBERON:0001476	86.68	gold quality
muscle of leg	UBERON:0001383	86.48	gold quality
tonsil	UBERON:0002372	86.03	gold quality
smooth muscle tissue	UBERON:0001135	85.98	gold quality
tendon	UBERON:0000043	85.70	gold quality
lower esophagus	UBERON:0013473	85.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.70	gold quality
mucosa of stomach	UBERON:0001199	85.61	gold quality
germinal epithelium of ovary	UBERON:0001304	85.61	gold quality
skeletal muscle organ	UBERON:0014892	85.39	gold quality
parotid gland	UBERON:0001831	85.13	gold quality
parietal pleura	UBERON:0002400	85.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.95	gold quality
skin of abdomen	UBERON:0001416	84.94	gold quality
vermiform appendix	UBERON:0001154	84.83	gold quality
bone marrow	UBERON:0002371	84.73	gold quality
lymph node	UBERON:0000029	84.68	gold quality
skin of leg	UBERON:0001511	84.64	gold quality
body of pancreas	UBERON:0001150	84.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

173 targeting RIC1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 56.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• These results suggest that the newly identified domain is essential for the proper phosphorylation and localization of Cx43, and CIP150 is a novel partner protein targeting this domain. (PMID:16112082)
• KIAA1432 is a novel gene activated by amplification in Small Cell Lung Cancers. (PMID:23716474)
• reduced genetically determined expression of RIC1 is associated with musculoskeletal and dental conditions. (PMID:31932796)
• Genome-wide analysis of copy-number variation in humans with cleft lip and/or cleft palate identifies COBLL1, RIC1, and ARHGEF38 as clefting genes. (PMID:36493769)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000108298
mus_musculus	Ric1	ENSMUSG00000038658
rattus_norvegicus	Ric1	ENSRNOG00000016172
drosophila_melanogaster	Rich	FBGN0028500
caenorhabditis_elegans		WBGENE00011071

Protein

Protein identifiers

Guanine nucleotide exchange factor subunit RIC1 — Q4ADV7 (reviewed: Q4ADV7)

Alternative names: Connexin-43-interacting protein of 150 kDa, Protein RIC1 homolog, RAB6A-GEF complex partner protein 1

All UniProt accessions (4): Q4ADV7, H0YFD4, H0YFN7, H0YGC4

UniProt curated annotations — full annotation on UniProt →

Function. The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP, and may thereby be required for efficient fusion of endosome-derived vesicles with the Golgi compartment. The RIC1-RGP1 complex participates in the recycling of mannose-6-phosphate receptors. Required for phosphorylation and localization of GJA1. Is a regulator of procollagen transport and secretion, and is required for correct cartilage morphogenesis and development of the craniofacial skeleton.

Subunit / interactions. Forms a complex with RGP1; the interaction enhances RAB6A GTPase activity. Interacts (via central domain) with RGP1. Interacts with RAB6A; the interaction is direct with a preference for RAB6A-GDP. Interacts (via C-terminus domain) with RAB33B; the interaction is direct with a preference for RAB33B-GTP. Interacts with GJA1.

Subcellular location. Cytoplasm. Cytosol. Membrane.

Tissue specificity. Present in kidney and various cell lines (at protein level). Widely expressed at low level.

Disease relevance. CATIFA syndrome (CATIFA) [MIM:618761] An autosomal recessive disorder characterized by global developmental delay, intellectual disability, and behavioral abnormalities with mild to severe attention deficit-hyperactivity disorder. Motor, speech and cognitive deficits range from mild to severe. Patients show craniofacial dysmorphism including elongated face, short, broad upturned nose with anteverted nares and long philtrum. Additional clinical features are cleft lip/palate, tooth abnormalities, and visual impairment due to cataract, strabismus and poor visual tracking. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the RIC1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q4ADV7-1	1	yes
Q4ADV7-2	2
Q4ADV7-3	3

RefSeq proteins (3): NP_001129392, NP_001193486, NP_065880* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009771	RIC1_C	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR040096	Ric1	Family

Pfam: PF07064, PF25440

UniProt features (24 total): modified residue 7, compositionally biased region 4, splice variant 3, sequence conflict 3, repeat 2, sequence variant 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4ADV7-F1	73.43	0.37

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 (7): 996, 1015, 1017, 1019, 1037, 1172, 992

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6811438	Intra-Golgi traffic
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 255 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOCC_TRANS_GOLGI_NETWORK, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (6): regulation of extracellular matrix constituent secretion (GO:0003330), intracellular protein transport (GO:0006886), retrograde transport, endosome to Golgi (GO:0042147), negative regulation of protein catabolic process (GO:0042177), positive regulation of GTPase activity (GO:0043547), cranial skeletal system development (GO:1904888)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (7): Golgi membrane (GO:0000139), cytosol (GO:0005829), membrane (GO:0016020), trans-Golgi network membrane (GO:0032588), protein-containing complex (GO:0032991), Ric1-Rgp1 guanyl-nucleotide exchange factor complex (GO:0034066), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	2
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
Golgi apparatus	2
extracellular matrix constituent secretion	1
regulation of extracellular matrix organization	1
regulation of secretion by cell	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
anatomical structure development	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
GTPase binding	1
binding	1
bounding membrane of organelle	1
cytoplasm	1
trans-Golgi network	1
organelle membrane	1
cellular_component	1
guanyl-nucleotide exchange factor complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIC1	RAB33B	Q9H082	799
RIC1	COG8	Q96MW5	745
RIC1	COG3	Q96JB2	730
RIC1	GJA1	P17302	692
RIC1	BRD10	Q5HYC2	679
RIC1	ERMP1	Q7Z2K6	659
RIC1	RAB6A	P20340	657
RIC1	COG1	Q8WTW3	614
RIC1	COG2	Q14746	595
RIC1	COG7	P83436	593
RIC1	COG5	Q9UP83	589
RIC1	RAB21	Q9UL25	574
RIC1	RAB32	Q13637	563
RIC1	RAB6B	Q9NRW1	552
RIC1	GJA4	P35212	549

IntAct

29 interactions, top by confidence:

A	B	Type	Score
RGP1	RIC1	psi-mi:“MI:0915”(physical association)	0.700
RIC1	RGP1	psi-mi:“MI:0915”(physical association)	0.700
RGP1	RIC1	psi-mi:“MI:0407”(direct interaction)	0.700
RAB6A	RIC1	psi-mi:“MI:0407”(direct interaction)	0.590
RAB33B	RIC1	psi-mi:“MI:0914”(association)	0.590
RIC1	RAB33B	psi-mi:“MI:0407”(direct interaction)	0.590
RAB33B	RIC1	psi-mi:“MI:0915”(physical association)	0.590
RAB6A	RIC1	psi-mi:“MI:0914”(association)	0.590
RAB6A	RIC1	psi-mi:“MI:0915”(physical association)	0.590
MAP1LC3B	RIC1	psi-mi:“MI:0407”(direct interaction)	0.440
MAP1LC3A	RIC1	psi-mi:“MI:0407”(direct interaction)	0.440
SYNGR1	TNPO2	psi-mi:“MI:0914”(association)	0.350
C1orf210	SPAG9	psi-mi:“MI:0914”(association)	0.350
EFNB2	TCAF2	psi-mi:“MI:0914”(association)	0.350
EPHA1	ENC1	psi-mi:“MI:0914”(association)	0.350
OCIAD1	DCTN6	psi-mi:“MI:0914”(association)	0.350
PACC1	IPO5	psi-mi:“MI:0914”(association)	0.350
RIC3	QSOX1	psi-mi:“MI:0914”(association)	0.350
S1PR3	STXBP3	psi-mi:“MI:0914”(association)	0.350
SLC27A2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
SLC27A4	IPO5	psi-mi:“MI:0914”(association)	0.350
SLC30A4	ESYT2	psi-mi:“MI:0914”(association)	0.350
CD247	RSL1D1	psi-mi:“MI:0914”(association)	0.350
BET1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
	RIC1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): RIC1 (Synthetic Lethality), RIC1 (Synthetic Lethality), RIC1 (Synthetic Lethality), RIC1 (Synthetic Lethality), RIC1 (Synthetic Lethality), RIC1 (Affinity Capture-RNA), RIC1 (Affinity Capture-RNA), RIC1 (Proximity Label-MS), RIC1 (Proximity Label-MS), RIC1 (Affinity Capture-RNA), RIC1 (Proximity Label-MS), RIC1 (Proximity Label-MS), RIC1 (Proximity Label-MS), RIC1 (Proximity Label-MS), RIC1 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IC37, A1A4K3, A2CEI4, B1WC10, E9PY46, F1QEB7, F4IDS7, O08658, O13046, O75694, O75717, O95876, P33194, P37199, P59328, Q08D69, Q10569, Q10570, Q16531, Q32NR9, Q3U1J4, Q4ADV7, Q566H4, Q5DQR4, Q5R649, Q5U1Z0, Q5ZLG9, Q6P6Z0, Q6PGF3, Q6PJI9, Q7XWP1, Q802U2, Q805F9, Q8BMG7, Q8C0M0, Q8C456, Q8CEC0, Q8CJF7, Q8K1X1, Q8NFP9

Diamond homologs: A0A2R8QPS5, Q4ADV7, Q69ZJ7, Q9V3C5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	163
Likely benign	26
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1527482	GRCh37/hg19 9p24.3-22.3(chr9:203861-14322268)	Pathogenic

SpliceAI

4790 predictions. Top by Δscore:

Variant	Effect	Δscore
9:5629449:GCCGA:G	donor_gain	1.0000
9:5629452:GA:G	donor_gain	1.0000
9:5629454:G:GG	donor_gain	1.0000
9:5656573:A:AG	acceptor_gain	1.0000
9:5656574:A:G	acceptor_gain	1.0000
9:5656579:A:AG	acceptor_gain	1.0000
9:5656580:C:G	acceptor_gain	1.0000
9:5656581:A:AG	acceptor_gain	1.0000
9:5656582:G:GG	acceptor_gain	1.0000
9:5656582:GCCTA:G	acceptor_gain	1.0000
9:5656687:ATCAG:A	donor_loss	1.0000
9:5656688:TCAGT:T	donor_loss	1.0000
9:5656689:CAGTA:C	donor_loss	1.0000
9:5656690:AGTA:A	donor_loss	1.0000
9:5656691:G:GG	donor_gain	1.0000
9:5656692:T:A	donor_loss	1.0000
9:5656693:AAG:A	donor_loss	1.0000
9:5689954:TTCA:T	acceptor_loss	1.0000
9:5689955:TCAG:T	acceptor_loss	1.0000
9:5689956:CAG:C	acceptor_loss	1.0000
9:5689957:A:AG	acceptor_gain	1.0000
9:5689957:AGAC:A	acceptor_gain	1.0000
9:5689958:G:GA	acceptor_gain	1.0000
9:5689958:GAC:G	acceptor_gain	1.0000
9:5689958:GACG:G	acceptor_gain	1.0000
9:5690036:CAA:C	donor_gain	1.0000
9:5690037:AA:A	donor_gain	1.0000
9:5690037:AAGT:A	donor_loss	1.0000
9:5690038:AGTA:A	donor_loss	1.0000
9:5690039:G:C	donor_loss	1.0000

AlphaMissense

9381 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:5753620:T:A	W526R	1.000
9:5753620:T:C	W526R	1.000
9:5763531:T:C	L835P	1.000
9:5763615:T:C	L863P	1.000
9:5763623:C:G	H866D	1.000
9:5763633:T:C	L869P	1.000
9:5763696:T:C	F890S	1.000
9:5763729:T:A	V901D	1.000
9:5763737:T:C	C904R	1.000
9:5763738:G:A	C904Y	1.000
9:5763739:T:G	C904W	1.000
9:5763741:C:A	A905D	1.000
9:5763744:G:C	R906T	1.000
9:5763744:G:T	R906M	1.000
9:5763745:G:C	R906S	1.000
9:5763745:G:T	R906S	1.000
9:5763746:A:G	K907E	1.000
9:5763748:G:C	K907N	1.000
9:5763748:G:T	K907N	1.000
9:5763764:T:A	W913R	1.000
9:5763764:T:C	W913R	1.000
9:5763766:G:C	W913C	1.000
9:5763766:G:T	W913C	1.000
9:5763774:T:C	L916P	1.000
9:5763776:T:C	F917L	1.000
9:5763778:T:A	F917L	1.000
9:5763778:T:G	F917L	1.000
9:5763817:T:G	C930W	1.000
9:5763843:C:A	A939D	1.000
9:5763855:T:A	L943H	1.000

dbSNP variants (sampled 300 via entrez): RS1000005469 (9:5744065 T>C), RS1000007067 (9:5635339 T>A,C), RS1000015801 (9:5643815 T>A), RS1000020416 (9:5761220 T>C), RS1000037977 (9:5666423 T>G), RS1000049221 (9:5778863 T>C), RS1000057495 (9:5696984 C>G), RS1000063671 (9:5654046 C>G,T), RS1000108806 (9:5739244 G>C,T), RS1000110210 (9:5774658 T>C), RS1000114900 (9:5657074 G>A), RS1000118036 (9:5651168 T>C), RS1000121641 (9:5692349 C>G), RS1000145735 (9:5726719 T>TC), RS1000218170 (9:5650972 G>A)

Disease associations

OMIM: gene MIM:610354 | disease phenotypes: MIM:618761

GenCC curated gene-disease

Disease	Classification	Inheritance
cleft lip/palate	Strong	Autosomal dominant
Catifa syndrome	Moderate	Autosomal recessive

Mondo (2): Catifa syndrome (MONDO:0032901), cleft lip/palate (MONDO:0016044)

Orphanet (0):

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000220	Velopharyngeal insufficiency
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000327	Hypoplasia of the maxilla
HP:0000343	Long philtrum
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000519	Developmental cataract
HP:0000646	Amblyopia
HP:0000684	Delayed eruption of teeth
HP:0000689	Dental malocclusion
HP:0000692	Tooth malposition
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001611	Hypernasal speech
HP:0002033	Poor suck
HP:0002099	Asthma
HP:0002360	Sleep disturbance
HP:0004395	Malnutrition
HP:0006292	Abnormality of dental eruption
HP:0006342	Peg-shaped maxillary lateral incisors
HP:0007018	Attention deficit hyperactivity disorder

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST008403_24	Arterial stiffness index	7.000000e-07
GCST008916_119	Asthma	1.000000e-15
GCST010463_16	Childhood ALL/LBL (acute lymphoblastic leukemia/lymphoblastic lymphoma) treatment-related venous thromboembolism	4.000000e-06
GCST011353_52	Serum alkaline phosphatase levels	4.000000e-08
GCST012488_14	L1-L4 bone mineral density x serum urate levels interaction	8.000000e-06
GCST90011900_215	Serum alkaline phosphatase levels	3.000000e-32

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004517	arterial stiffness measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
trichostatin A	affects expression	1
2-butenal	decreases expression	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Hydrogen Peroxide	increases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Plant Extracts	increases expression, affects cotreatment	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7YN	HAP1 RIC1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04234971	PHASE4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	PHASE4	RECRUITING	Ketorolac in Palatoplasty
NCT03766217	PHASE3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	PHASE3	RECRUITING	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT00930124	PHASE2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT06408337	PHASE1/PHASE2	RECRUITING	Phase I-IIa, to Evaluate the Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Cleft Palate.
NCT00070811	Not specified	COMPLETED	Assessing the Results of Lip Surgery in Patients With Cleft Lip and Palate
NCT00156442	Not specified	COMPLETED	A Study to Examine the Relationship Between Sleep Apnea and Cleft Lip/Palate
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01871623	Not specified	UNKNOWN	One-Piece Le Fort I Osteotomy Versus Segmental Le Fort I Osteotomy
NCT01932164	Not specified	COMPLETED	Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT02789787	Not specified	COMPLETED	Clinical Effectiveness of Late Maxillary Protraction for Cleft Lip and Palate
NCT02845193	Not specified	COMPLETED	Effect of Novel Nasoalveolar Molding Techniques on Parents’ Satisfaction and Short Term Treatment Outcomes in Unilateral Cleft Lip and Palate Infants: A Randomized Controlled Trial
NCT02881606	Not specified	COMPLETED	Evaluation of the Clinical Effectiveness of Naso-alveolar Molding (NAM) Versus Computer Aided Design NAM (CAD/NAM) in Infants With Bilateral Cleft Lip and Palate: A Randomized Clinical Trial
NCT03011489	Not specified	UNKNOWN	Parent’s Satisfaction and Evaluation of Postsurgical Outcomes in Unilateral Cleft Lip / Palate Newly Born Infants With / Without Vacuum Formed Nasoalveolar Molding Aligners : A Controlled Clinical Trial
NCT03065686	Not specified	RECRUITING	Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing
NCT03165331	Not specified	UNKNOWN	Online Psychosocial Support for Young People With a Visible Difference: A Randomised Control Study
NCT03217890	Not specified	UNKNOWN	the Relationship Between Cleft Lip and / or Palate (Different Types) and ABO Blood Groups.
NCT03308266	Not specified	COMPLETED	Electromyographic Analysis of the Masticatory Muscles in Cleft Lip and Palate Children With Temporomandibular Disorders
NCT03395015	Not specified	COMPLETED	Efficacy of Maxillo-facial Treatment on Cleft Lip and Palate Patients Faces: Aesthetic Considerations
NCT03514563	Not specified	TERMINATED	Three Dimensional Facial Growth Analysis
NCT03563495	Not specified	COMPLETED	Tissue Engineered Constructs for Alveolar Cleft Repair
NCT03582111	Not specified	COMPLETED	Ultrasound Diagnosis of Cleft Lip and Palate
NCT03686761	Not specified	COMPLETED	Periodontal Changes Following Mid Maxillary Distraction
NCT03708406	Not specified	COMPLETED	Otologic and Rhinologic Outcomes in Children With Clef Palate
NCT03740841	Not specified	TERMINATED	Evaluation of the Effects of LUNII on Pre-operative Anxiety and on the Post-operative Period in Children With Cleft Lip and Palate Admitted for Alveolar Bone Graft: Pilot Study
NCT03750708	Not specified	WITHDRAWN	Oral Hygiene and Connected Toothbrush Before Alveolar Bone Graft for Cleft Lip and Palate
NCT03839290	Not specified	UNKNOWN	Development of the Palate in Bilateral Orofacial Cleft Newborns One Year After Early Neonatal Cheiloplasty
NCT03877666	Not specified	COMPLETED	Assessment of the Influence of Cleft Repair on Microcirculation of the Palate
NCT03976609	Not specified	COMPLETED	Three Dimensional Changes on Nasal Septum and Alveolar Cleft After Maxillary Expansion
NCT04108416	Not specified	COMPLETED	Unilateral Cleft Repair in One Surgery With Pure Primary Healing
NCT04236466	Not specified	UNKNOWN	Transverse Dento-skeletal Effects of Two Rapid Palatal Expansion Appliances in Cleft Lip and Palate Patients
NCT04331379	Not specified	COMPLETED	Effectiveness of Nasal-alar Elevator Combined With Taping Vs. Taping Alone on Improving the Nose Esthetics and Maxillary Arch Dimensions in Infants With Unilateral Complete Cleft Lip and Palate
NCT04331977	Not specified	COMPLETED	Effectiveness of Two Maxillary Expanders in Improving the Transverse Skeletal and Dental Dimensions in Patients With Cleft Lip and Palate
NCT04354116	Not specified	UNKNOWN	MARPE in Patients With Cleft Lip and Palate
NCT04369638	Not specified	TERMINATED	Fabrication of Naso-alveolar Molding (NAM) Appliance in Cleft Lip and Palate (CLP) From Digital Magnetic Resonance Imaging (MRI) Face Scan
NCT04381078	Not specified	UNKNOWN	Methods of Providing Information Prior to an Alveolar Bone Graft
NCT04384276	Not specified	COMPLETED	Weigh Easy: Simplifying Home Weight Monitoring for Infants
NCT04422847	Not specified	RECRUITING	Use of Computer Aided Design and 3D Printing for Anesthesiology Management in a Pediatric Patient With Cleft Facial Defect