ARHGAP29

Summary

ARHGAP29 (Rho GTPase activating protein 29, HGNC:30207) is a protein-coding gene on chromosome 1p22.1, encoding Rho GTPase-activating protein 29 (Q52LW3). GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

Rap1 is a small GTPase that, through effectors, regulates Rho GTPase signaling. These effectors- Rasip1, Radil, and the protein encoded by this gene- translocate to the cell membrane, where they form a multiprotein complex. This complex is necessary for Rap1-induced inhibition of Rho signaling. Defects in this gene may be a cause of nonsyndromic cleft lip with or without cleft palate.

Source: NCBI Gene 9411 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ARHGAP29-related non-syndromic orofacial cleft (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 227 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_004815

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30207
Approved symbol	ARHGAP29
Name	Rho GTPase activating protein 29
Location	1p22.1
Locus type	gene with protein product
Status	Approved
Aliases	PARG1
Ensembl gene	ENSG00000137962
Ensembl biotype	protein_coding
OMIM	610496
Entrez	9411

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000260526, ENST00000370217, ENST00000482481, ENST00000546444, ENST00000552844, ENST00000860621, ENST00000918397, ENST00000918398, ENST00000946813, ENST00000946814, ENST00000946815

RefSeq mRNA: 5 — MANE Select: NM_004815 NM_001328664, NM_001328665, NM_001328666, NM_001328667, NM_004815

CCDS: CCDS748

Canonical transcript exons

ENST00000260526 — 23 exons

Exon	Start	End
ENSE00000932136	94177612	94177720
ENSE00000932145	94189926	94190083
ENSE00000932146	94201720	94201857
ENSE00000932147	94202544	94202732
ENSE00000932150	94203930	94203994
ENSE00000932151	94205061	94205198
ENSE00000932152	94205635	94205683
ENSE00000932153	94208832	94208904
ENSE00000932154	94209254	94209350
ENSE00001158110	94220258	94220392
ENSE00001180170	94202918	94202998
ENSE00001180174	94203100	94203210
ENSE00001180201	94168905	94174749
ENSE00001180206	94231407	94231643
ENSE00001920859	94237415	94237584
ENSE00003467206	94177852	94178167
ENSE00003517348	94189216	94189352
ENSE00003564274	94186499	94186597
ENSE00003595265	94179725	94179957
ENSE00003624020	94185342	94185481
ENSE00003633414	94188837	94188941
ENSE00003666360	94184151	94184288
ENSE00003681651	94184872	94185060

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.2846 / max 596.0511, expressed in 1409 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13382	21.9008	1379
13385	9.0522	1236
13384	1.1273	471
201579	0.2044	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
visceral pleura	UBERON:0002401	98.30	gold quality
parietal pleura	UBERON:0002400	97.94	gold quality
pleura	UBERON:0000977	97.78	gold quality
renal medulla	UBERON:0000362	97.47	gold quality
renal glomerulus	UBERON:0000074	97.18	gold quality
metanephric glomerulus	UBERON:0004736	97.01	gold quality
skin of hip	UBERON:0001554	96.89	gold quality
parotid gland	UBERON:0001831	96.76	gold quality
vena cava	UBERON:0004087	96.73	gold quality
calcaneal tendon	UBERON:0003701	96.69	gold quality
upper leg skin	UBERON:0004262	96.54	gold quality
pericardium	UBERON:0002407	96.37	gold quality
mammary duct	UBERON:0001765	96.28	gold quality
synovial joint	UBERON:0002217	96.28	gold quality
lower lobe of lung	UBERON:0008949	96.22	gold quality
urethra	UBERON:0000057	96.18	gold quality
epithelium of mammary gland	UBERON:0003244	96.15	gold quality
kidney epithelium	UBERON:0004819	95.64	gold quality
metanephros	UBERON:0000081	95.20	gold quality
seminal vesicle	UBERON:0000998	95.04	gold quality
mammary gland	UBERON:0001911	95.01	gold quality
thoracic mammary gland	UBERON:0005200	95.01	gold quality
saphenous vein	UBERON:0007318	94.99	gold quality
nephron tubule	UBERON:0001231	94.76	gold quality
heart right ventricle	UBERON:0002080	94.22	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.90	gold quality
blood vessel layer	UBERON:0004797	93.84	gold quality
germinal epithelium of ovary	UBERON:0001304	93.79	gold quality
penis	UBERON:0000989	93.61	gold quality
superficial temporal artery	UBERON:0001614	93.42	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	1045.48
E-HCAD-25	yes	727.22
E-MTAB-10855	yes	715.80
E-MTAB-6108	yes	608.27
E-MTAB-9154	yes	566.47
E-MTAB-8142	yes	119.87
E-MTAB-10287	yes	72.08
E-HCAD-1	yes	44.75
E-HCAD-10	yes	41.39
E-HCAD-11	yes	39.57
E-MTAB-6701	yes	36.18
E-MTAB-8410	yes	29.78
E-CURD-46	yes	28.67
E-HCAD-35	yes	24.85
E-GEOD-135922	yes	23.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

234 targeting ARHGAP29, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Literature-anchored findings (GeneRIF, showing 16)

• PARG1 expression was substantially reduced & it displayed at least partial promoter methylation in all investigated mantle-cell lines & in 31 primary cases. PARG1 is a strong candidate tumor suppressor gene in MCL. (PMID:17488656)
• ARHGAP29 is the etiologic gene for the cleft lip with or without cleft palate locus identified by genome-wide association on chromosome 1p22. (PMID:23008150)
• Rasip1-ArhGAP29 pathway also functions in Rap1-mediated regulation of endothelial junctions, which controls endothelial barrier function (PMID:23798437)
• We identified genetic variants in TGFB3 and ARHGAP29 associated with suboptimal healing outcome. (PMID:24635173)
• Genetic variants in ARHGAP29 contribute to the development of nonsyndromic cleft lip with cleft palate. (PMID:25163644)
• Data indicate that through GTPase-activating proteins ArhGAP29 complex formation Rap1 GTP-binding protein spatially restricts Rho-mediated signaling, which is necessary for endothelial barrier potentiation. (PMID:25963656)
• The of loss-of-function and ARHGAP29 missense variants in the etiology of oral clefts (PMID:27350171)
• The variant in question segregates as an autosomal dominant trait caused by an heterozygous missense variant in ARHGAP29 (p.Ser552Pro) that had not previously been identified in a population genomic databases. The p.Ser552Pro ARHGAP29 variant was not present in genomic databases and was predicted to be pathogenic by multiple in silico programs. (PMID:28029220)
• Risk haplotypes affect ARHGAP29 expression causing non-syndromic orofacial clefting. (PMID:28287101)
• YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. (PMID:28538170)
• The SNP rs560426 Within ABCA4-ARHGAP29 Locus and the Risk of Nonsyndromic Oral Clefts. (PMID:31950859)
• ARHGAP29 expression may be a novel prognostic factor of cell proliferation and invasion in prostate cancer. (PMID:33125156)
• Identification of a Novel Variant of ARHGAP29 in a Chinese Family with Nonsyndromic Cleft Lip and Palate. (PMID:33150183)
• Influence of ARHGAP29 on the Invasion of Mesenchymal-Transformed Breast Cancer Cells. (PMID:33291460)
• TBX21 attenuates colorectal cancer progression via an ARHGAP29/RSK/GSK3beta dependent manner. (PMID:37067748)
• ARHGAP29 Is Involved in Increased Invasiveness of Tamoxifen-resistant Breast Cancer Cells and its Expression Levels Correlate With Clinical Tumor Parameters of Breast Cancer Patients. (PMID:38944420)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap29b	ENSDARG00000017748
danio_rerio	arhgap29a	ENSDARG00000026329
mus_musculus	Arhgap29	ENSMUSG00000039831
caenorhabditis_elegans		WBGENE00014051

Paralogs (2): GMIP (ENSG00000089639), ARHGAP45 (ENSG00000180448)

Protein

Protein identifiers

Rho GTPase-activating protein 29 — Q52LW3 (reviewed: Q52LW3)

Alternative names: PTPL1-associated RhoGAP protein 1, Rho-type GTPase-activating protein 29

All UniProt accessions (2): Q52LW3, F8VWZ8

UniProt curated annotations — full annotation on UniProt →

Function. GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. May act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis.

Subunit / interactions. Interacts with PTPN13/PTPL1. Interacts with RAP2A via its coiled coil domain. Interacts with RASIP1.

Tissue specificity. Widely expressed. Highly expressed in skeletal muscle and heart. Expressed at intermediate level in placenta, liver and pancreas. Weakly expressed in brain, lung and kidney.

Induction. Strongly down-regulated in mantle-cell lymphomas. Up-regulated in migrating glioma cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q52LW3-1	1	yes
Q52LW3-2	2

RefSeq proteins (5): NP_001315593, NP_001315594, NP_001315595, NP_001315596, NP_004806* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR031160	F_BAR_dom	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR051025	RhoGAP	Family
IPR054713	GMIP/FCHO2-like_FCH	Domain
IPR057028	RHG29_45_N	Domain

Pfam: PF00130, PF00620, PF22699, PF24235

UniProt features (45 total): sequence conflict 13, modified residue 12, region of interest 6, compositionally biased region 3, sequence variant 3, domain 2, splice variant 2, chain 1, coiled-coil region 1, site 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q52LW3-F1	64.41	0.38

Functional residue map

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

Catalytic / active sites (1): 707 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (12): 171, 176, 179, 190, 499, 519, 552, 913, 949, 1019, 1144, 1146

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 315 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, KMCATNNWGGA_UNKNOWN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, AAAGGGA_MIR204_MIR211, RFX1_02, CUI_TCF21_TARGETS_2_DN, YANAGIHARA_ESX1_TARGETS, IK3_01

GO Biological Process (4): Rho protein signal transduction (GO:0007266), regulation of small GTPase mediated signal transduction (GO:0051056), negative regulation of small GTPase mediated signal transduction (GO:0051058), signal transduction (GO:0007165)

GO Molecular Function (5): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), PDZ domain binding (GO:0030165), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
small GTPase-mediated signal transduction	3
cellular anatomical structure	2
regulation of intracellular signal transduction	1
regulation of small GTPase mediated signal transduction	1
negative regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
protein domain specific binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
cellular_component	1

Protein interactions and networks

STRING

1132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP29	RAP2A	P10114	952
ARHGAP29	RASIP1	Q5U651	942
ARHGAP29	PARG	Q86W56	862
ARHGAP29	PTPN13	Q12923	861
ARHGAP29	CDC42	P21181	639
ARHGAP29	IRF6	O14896	632
ARHGAP29	GRHL3	Q8TE85	559
ARHGAP29	ABCA4	P78363	545
ARHGAP29	AFDN	P55196	528
ARHGAP29	RHOA	P06749	509
ARHGAP29	VAX1	Q5SQQ9	505
ARHGAP29	XRCC1	P18887	477
ARHGAP29	ARHGAP28	Q9P2N2	476
ARHGAP29	STIP1	P31948	475
ARHGAP29	MAL2	Q969L2	442

IntAct

40 interactions, top by confidence:

A	B	Type	Score
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
GPR183	NRP1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
ACOT8	PML	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
SIRT1	KPNA3	psi-mi:“MI:0915”(physical association)	0.400
MAGEA11	ARHGAP29	psi-mi:“MI:0915”(physical association)	0.370
KDM1A	ARHGAP29	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
ARHGAP29	IPO5	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CAMK2G	PSMD12	psi-mi:“MI:0914”(association)	0.350
FGFR1	NDUFA4	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
AURKB	VWA8	psi-mi:“MI:0914”(association)	0.350
CD244	VGF	psi-mi:“MI:0914”(association)	0.350
EFNB2	TCAF2	psi-mi:“MI:0914”(association)	0.350
FZD10	PDE2A	psi-mi:“MI:0914”(association)	0.350
HPN	DDX39A	psi-mi:“MI:0914”(association)	0.350
NAA10	SUPT5H	psi-mi:“MI:0914”(association)	0.350
PTGER3	ECD	psi-mi:“MI:0914”(association)	0.350
RPS24	AP3B1	psi-mi:“MI:0914”(association)	0.350
SCN2B	RIMOC1	psi-mi:“MI:0914”(association)	0.350
SSTR2	PJA2	psi-mi:“MI:0914”(association)	0.350
SYT1	AP3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (106): ARHGAP29 (Affinity Capture-MS), HERC1 (Affinity Capture-MS), ARHGAP29 (Two-hybrid), ARHGAP29 (Proximity Label-MS), ARHGAP29 (Affinity Capture-MS), ARHGAP29 (Proximity Label-MS), ARHGAP29 (Affinity Capture-MS), ARHGAP29 (Affinity Capture-MS), ARHGAP29 (Affinity Capture-MS), ARHGAP29 (Affinity Capture-RNA), ARHGAP29 (Proximity Label-MS), ARHGAP29 (Reconstituted Complex), ARHGAP29 (Proximity Label-MS), ARHGAP29 (Proximity Label-MS), ARHGAP29 (Proximity Label-MS)

ESM2 similar proteins: A2VDP1, A4FV29, A4II15, A4II71, A7YY57, A9ULY7, E1C760, F6Y9J3, Q15545, Q1LZE0, Q28DG8, Q28HX4, Q2HJG8, Q32KY1, Q3U1T3, Q4R5A5, Q4V8V1, Q52LW3, Q5DTM8, Q5EA95, Q5M7T3, Q5PSV4, Q5R7L9, Q5RHQ8, Q5VTR2, Q5XGX5, Q5ZKF4, Q5ZLL9, Q62739, Q6AZT4, Q6DFL5, Q6IVW0, Q6R1L1, Q7Z569, Q7ZXA8, Q8BXG3, Q8CG73, Q8CGF1, Q8IZC4, Q8K0Q5

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ARHGAP29	“down-regulates activity”	RHOA	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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
Infectious disease	11	6.3×	4e-04
Membrane Trafficking	7	6.0×	9e-03
Viral Infection Pathways	8	5.7×	9e-03
Vesicle-mediated transport	7	5.7×	1e-02
Signaling by Rho GTPases	7	5.6×	1e-02
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	7	5.5×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	163
Likely benign	27
Benign	8

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
242340	NM_004815.4(ARHGAP29):c.1475C>A (p.Ser492Ter)	Pathogenic
242341	NM_004815.4(ARHGAP29):c.698-1G>C	Pathogenic
242343	NM_004815.4(ARHGAP29):c.2109+1G>A	Pathogenic
4086438	NM_004815.4(ARHGAP29):c.1939C>T (p.Arg647Ter)	Pathogenic
4538608	NM_004815.4(ARHGAP29):c.2547_2550dup (p.Ile851fs)	Pathogenic
625277	NM_004815.4(ARHGAP29):c.1920+1G>A	Pathogenic
2636567	NM_004815.4(ARHGAP29):c.2481-1G>A	Likely pathogenic

SpliceAI

3124 predictions. Top by Δscore:

Variant	Effect	Δscore
1:94174745:TTTGT:T	acceptor_gain	1.0000
1:94174746:TTGT:T	acceptor_gain	1.0000
1:94174747:TGT:T	acceptor_gain	1.0000
1:94174748:GT:G	acceptor_gain	1.0000
1:94174748:GTC:G	acceptor_loss	1.0000
1:94174750:C:CC	acceptor_gain	1.0000
1:94174750:CT:C	acceptor_loss	1.0000
1:94174751:T:G	acceptor_loss	1.0000
1:94177603:GCTAC:G	donor_loss	1.0000
1:94177604:CTACT:C	donor_loss	1.0000
1:94177606:ACT:A	donor_loss	1.0000
1:94177607:CT:C	donor_loss	1.0000
1:94177608:TCA:T	donor_loss	1.0000
1:94177609:CACCA:C	donor_loss	1.0000
1:94177610:A:AC	donor_gain	1.0000
1:94177610:AC:A	donor_gain	1.0000
1:94177611:C:CC	donor_gain	1.0000
1:94177611:CC:C	donor_gain	1.0000
1:94177611:CCA:C	donor_gain	1.0000
1:94177850:A:AC	donor_gain	1.0000
1:94177850:ACTT:A	donor_gain	1.0000
1:94177851:C:CC	donor_gain	1.0000
1:94177851:CTT:C	donor_gain	1.0000
1:94177851:CTTC:C	donor_gain	1.0000
1:94177853:T:TA	donor_gain	1.0000
1:94179958:C:CC	acceptor_gain	1.0000
1:94185335:ATCTT:A	donor_loss	1.0000
1:94185336:TCTTA:T	donor_loss	1.0000
1:94185337:CTTA:C	donor_loss	1.0000
1:94185338:TTACC:T	donor_loss	1.0000

AlphaMissense

8349 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:94178138:A:G	M837T	0.999
1:94179731:A:G	L825P	0.999
1:94184278:C:G	R707P	0.999
1:94185010:A:C	C657W	0.999
1:94185012:A:G	C657R	0.999
1:94185060:A:G	C641R	0.999
1:94185350:A:G	C638R	0.999
1:94185391:C:G	C624S	0.999
1:94185392:A:G	C624R	0.999
1:94185392:A:T	C624S	0.999
1:94185425:G:C	H613D	0.999
1:94185433:G:T	A610D	0.999
1:94201848:C:G	A385P	0.999
1:94178099:A:G	L850P	0.998
1:94178121:C:A	G843W	0.998
1:94179754:A:C	S817R	0.998
1:94179754:A:T	S817R	0.998
1:94179756:T:G	S817R	0.998
1:94184279:G:T	R707S	0.998
1:94184288:C:G	G704R	0.998
1:94184288:C:T	G704R	0.998
1:94185011:C:G	C657S	0.998
1:94185011:C:T	C657Y	0.998
1:94185012:A:T	C657S	0.998
1:94185036:A:G	C649R	0.998
1:94185059:C:G	C641S	0.998
1:94185060:A:T	C641S	0.998
1:94185348:A:C	C638W	0.998
1:94185349:C:G	C638S	0.998
1:94185350:A:T	C638S	0.998

dbSNP variants (sampled 300 via entrez): RS1000008018 (1:94305978 C>G,T), RS1000042708 (1:94207720 T>C,G), RS1000064480 (1:94214181 T>C), RS1000082687 (1:94208661 T>C), RS1000084143 (1:94254718 T>G), RS1000094539 (1:94262632 G>A,C), RS1000095187 (1:94213962 G>A), RS1000101841 (1:94300892 G>A), RS1000104325 (1:94206489 T>G), RS1000126355 (1:94300490 C>T), RS1000146878 (1:94210214 A>G), RS1000147329 (1:94288860 T>C), RS1000168677 (1:94191051 C>T), RS1000178887 (1:94288452 G>A), RS1000242363 (1:94252193 A>G)

Disease associations

OMIM: gene MIM:610496 | disease phenotypes: MIM:119540

GenCC curated gene-disease

Disease	Classification	Inheritance
orofacial cleft	Definitive	Autosomal dominant
cleft lip with or without cleft palate	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ARHGAP29-related non-syndromic orofacial cleft	Definitive	AD

Mondo (4): isolated cleft palate (MONDO:0007336), cleft palate (MONDO:0016064), orofacial cleft (MONDO:0000358), (MONDO:0016034)

Orphanet (1): Cleft palate (Orphanet:2014)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000220	Velopharyngeal insufficiency
HP:0000327	Hypoplasia of the maxilla
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000689	Dental malocclusion
HP:0000750	Delayed speech and language development
HP:0001611	Hypernasal speech
HP:0002033	Poor suck
HP:0004395	Malnutrition
HP:0006292	Abnormality of dental eruption
HP:0006342	Peg-shaped maxillary lateral incisors
HP:0008872	Feeding difficulties in infancy
HP:0009088	Speech articulation difficulties
HP:0010294	Palate fistula
HP:0011044	Abnormal number of permanent teeth
HP:0100334	Unilateral cleft palate
HP:0100337	Bilateral cleft palate
HP:0200136	Oral-pharyngeal dysphagia
HP:0200153	Agenesis of lateral incisor

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001049_8	D-dimer levels	1.000000e-06
GCST006624_11	Systolic blood pressure	6.000000e-11
GCST90002400_40	Plateletcrit	1.000000e-14
GCST90011899_96	Aspartate aminotransferase levels	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004507	D dimer measurement
EFO:0006335	systolic blood pressure
EFO:0007985	platelet crit
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	6
bisphenol A	affects cotreatment, affects methylation, decreases expression, decreases methylation	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
entinostat	decreases expression, affects cotreatment	2
Quercetin	affects expression, increases phosphorylation	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
glycidyl methacrylate	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pinosylvin	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
rofecoxib	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00004639	PHASE2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT00760006	PHASE2	COMPLETED	Preventing Complications in Cleft Palate Repair With Antibiotics
NCT01760330	PHASE2	WITHDRAWN	IV Acetaminophen in Children Undergoing Palatoplasty
NCT02350803	PHASE2	COMPLETED	Does Use of Rigid Fixation After Removing Distraction Osteogenesis Device Reduce the Relapse?
NCT03412474	PHASE2	COMPLETED	Suprazygomatic Block in Cleft Palate Surgery in Children
NCT04342234	Not specified	RECRUITING	Neural Network to Calculate Morphology of the Cleft Palate to Reduce Cleft Lip and Palate Treatment Burden.
NCT05867862	Not specified	COMPLETED	Implementation of a Program to Strengthen Oral Hygiene in Patient With Cleft Deformities
NCT06880094	Not specified	RECRUITING	Study of Congenital Orofacial Clefts by Implementing Optical Genome Mapping
NCT07340008	Not specified	RECRUITING	Analgosedation With Ketamine, Nalbuphine, or Dexmedetomidine for Suture Removal in Children After Cleft Surgery
NCT07557576	Not specified	RECRUITING	Effect of Opioid-Free vs Opioid-Based Anesthesia on Postoperative Pain and Emergence Agitation in Children Undergoing Cleft Surgery
NCT01616953	PHASE1/PHASE2	COMPLETED	Cell Therapy for Craniofacial Bone Defects
NCT02247193	PHASE1/PHASE2	COMPLETED	Botulinum Toxin to Improve Cosmesis of Primary Cleft Lip Repair
NCT00097149	Not specified	COMPLETED	Systematic Pediatric Care for Oral Clefts - South America
NCT00285714	Not specified	UNKNOWN	3D Imaging of Hard and Soft Tissue in Orthognathic Surgery
NCT00340977	Not specified	COMPLETED	Svangerskap, Arv, Og Miljo (Pregnancy, Heredity and Environment)
NCT00423072	Not specified	COMPLETED	Middle Ear Pressure Disregulation in Cleft Palate Patients
NCT00584272	Not specified	COMPLETED	Retrospective Study on the Outcome of Cleft Palate Repair: Comparing US Surgical and Ethicon Suture Materials
NCT00773994	Not specified	COMPLETED	Pilot Study Evaluating Characteristic Closure Patterns of the Normal Velopharyngeal Portal
NCT00779961	Not specified	UNKNOWN	An Investigation for the Optimal Timing of a Cleft Palate Repair
NCT00829101	Not specified	COMPLETED	Articulation and Phonology in Children With Unilateral Cleft Lip and Palate
NCT00993551	Not specified	COMPLETED	Timing of Primary Surgery for Cleft Palate
NCT00993993	Not specified	COMPLETED	Relational Development in Children With Cleft Lips and Palates: Influence of the Waiting Period Prior to the First Surgical Intervention and the Parents’ Psychological Perception of the Abnormality
NCT01046591	Not specified	COMPLETED	Sleep and Behavior in Children With Cleft Palate
NCT01252264	Not specified	COMPLETED	FaceBase Biorepository
NCT01380171	Not specified	COMPLETED	Primary Palatoplasty in Pediatric Patients - A Retrospective Review of Surgical Outcomes
NCT01500109	Not specified	COMPLETED	Efficacy of Oral Versus Intravenous Acetaminophen for Primary Pediatric Cleft Palate Repair
NCT01535131	Not specified	COMPLETED	Furlow Palatoplasty With Tensor Tenopexy
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01867632	Not specified	COMPLETED	Acellular Dermal Matrix in Primary Palatoplasty
NCT02329509	Not specified	COMPLETED	Evaluation of Facial Growth in Two Primary Protocols Used in the Surgical Treatment of Unilateral Cleft Lip and Palate Patients
NCT02415361	Not specified	COMPLETED	Follow Ups of Parents With Infants With Cleft Lip and Palate