RALGDS

Summary

RALGDS (ral guanine nucleotide dissociation stimulator, HGNC:9842) is a protein-coding gene on chromosome 9q34.13-q34.2, encoding Ral guanine nucleotide dissociation stimulator (Q12967). Functions as a guanine nucleotide exchange factor (GEF) activating either RalA or RalB GTPases and plays an important role in intracellular transport.

Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes.

Source: NCBI Gene 5900 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 138 total
• MANE Select transcript: NM_006266

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9842
Approved symbol	RALGDS
Name	ral guanine nucleotide dissociation stimulator
Location	9q34.13-q34.2
Locus type	gene with protein product
Status	Approved
Aliases	RGF, RalGEF, RGDS
Ensembl gene	ENSG00000160271
Ensembl biotype	protein_coding
OMIM	601619
Entrez	5900

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 19 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay

ENST00000372047, ENST00000372050, ENST00000372062, ENST00000393157, ENST00000393160, ENST00000424572, ENST00000460587, ENST00000469972, ENST00000471109, ENST00000477660, ENST00000482648, ENST00000493067, ENST00000493438, ENST00000495621, ENST00000498797, ENST00000891838, ENST00000891839, ENST00000891840, ENST00000891841, ENST00000891842, ENST00000891843, ENST00000891844, ENST00000891845, ENST00000961509, ENST00000961510, ENST00000961511, ENST00000961512

RefSeq mRNA: 5 — MANE Select: NM_006266 NM_001042368, NM_001271774, NM_001271775, NM_001271776, NM_006266

CCDS: CCDS43897, CCDS65172, CCDS65173, CCDS65174, CCDS6959

Canonical transcript exons

ENST00000372050 — 18 exons

Exon	Start	End
ENSE00001804795	133109626	133109721
ENSE00002697290	133101520	133101762
ENSE00003459432	133103230	133103262
ENSE00003472443	133101938	133102139
ENSE00003497067	133106645	133106748
ENSE00003506123	133107085	133107300
ENSE00003512465	133105932	133106016
ENSE00003525467	133100268	133100382
ENSE00003530506	133103747	133103833
ENSE00003553365	133107988	133108406
ENSE00003573583	133102779	133102900
ENSE00003596372	133104263	133104331
ENSE00003666122	133102476	133102571
ENSE00003675804	133112042	133112152
ENSE00003681469	133108673	133108866
ENSE00003684996	133110296	133110489
ENSE00003848445	133120972	133121240
ENSE00003850732	133097722	133098762

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7903 / max 492.2215, expressed in 1808 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102941	10.4029	1513
102963	9.5449	1720
102964	2.1384	1126
102942	1.4707	823
102951	0.8128	118
102935	0.3999	60
102939	0.2944	161
102940	0.2494	116
205646	0.1457	69
102952	0.1162	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.39	gold quality
cerebellar hemisphere	UBERON:0002245	98.29	gold quality
cerebellar cortex	UBERON:0002129	98.27	gold quality
pituitary gland	UBERON:0000007	98.26	gold quality
cerebellum	UBERON:0002037	98.25	gold quality
adenohypophysis	UBERON:0002196	98.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.12	gold quality
cortical plate	UBERON:0005343	97.87	gold quality
skin of abdomen	UBERON:0001416	97.66	gold quality
zone of skin	UBERON:0000014	97.42	gold quality
skin of leg	UBERON:0001511	97.28	gold quality
substantia nigra	UBERON:0002038	97.24	gold quality
granulocyte	CL:0000094	97.10	gold quality
amygdala	UBERON:0001876	96.96	gold quality
temporal lobe	UBERON:0001871	96.95	gold quality
caudate nucleus	UBERON:0001873	96.94	gold quality
Ammon’s horn	UBERON:0001954	96.91	gold quality
putamen	UBERON:0001874	96.80	gold quality
corpus callosum	UBERON:0002336	96.72	gold quality
right frontal lobe	UBERON:0002810	96.59	gold quality
nucleus accumbens	UBERON:0001882	96.53	gold quality
brain	UBERON:0000955	96.52	gold quality
hypothalamus	UBERON:0001898	96.48	gold quality
right uterine tube	UBERON:0001302	96.28	gold quality
ganglionic eminence	UBERON:0004023	96.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.81	gold quality
gall bladder	UBERON:0002110	95.75	gold quality
primary visual cortex	UBERON:0002436	95.69	gold quality
minor salivary gland	UBERON:0001830	95.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, STAT3

miRNA regulators (miRDB)

93 targeting RALGDS, 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-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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1277-5P	100.00	73.95	5056
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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162

Literature-anchored findings (GeneRIF, showing 10)

• involved in regulation of choline kinase activity by Ras proteins (PMID:11840339)
• identified Ral-GDS as a beta-arrestin-binding protein by yeast two-hybrid screening and co-immunoprecipitation from human polymorphonuclear neutrophilic leukocytes (PMID:12105416)
• RALGDS has a role in attenuating p53-independent DNA damage G2 checkpoint (PMID:15208305)
• Merlin can function as a tumor suppressor by inhibiting the RalGDS-mediated oncogenic signals. (PMID:16007223)
• These data extend understanding of the functional roles of the Ral pathway and begin to identify signaling pathways relevant for organ-specific metastasis. (PMID:17709381)
• results of screening suggest that RALGDS is not mutationally altered in cutaneous melanoma (PMID:17992125)
• overexpression of RalGDS promotes exocytosis of Weibel-Palade bodies from endothelial cells (PMID:18417737)
• RalGDS and RalA act downstream of Rheb and that RalA activation is a crucial step in nutrient-induced mTORC1 activation (PMID:18948269)
• Studies provide models for Ras in association with Raf kinase, RalGDS and PI3Kalpha and PI3Kgamma. (PMID:19801192)
• Investigated is the role that electrostatic field differences caused by the charge reversal mutation Rap1A K31E play in determining the binding specificity of RalGDS to Rap1A versus Ras. (PMID:22738401)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ralgds	ENSDARG00000042409
mus_musculus	Ralgds	ENSMUSG00000026821
rattus_norvegicus	Ralgds	ENSRNOG00000010219

Paralogs (24): RASGRF1 (ENSG00000058335), RASGRP2 (ENSG00000068831), RAPGEF3 (ENSG00000079337), RAPGEF4 (ENSG00000091428), SOS2 (ENSG00000100485), RAPGEF1 (ENSG00000107263), RAPGEFL1 (ENSG00000108352), RAPGEF2 (ENSG00000109756), RASGRF2 (ENSG00000113319), SOS1 (ENSG00000115904), RALGPS2 (ENSG00000116191), RAPGEF5 (ENSG00000136237), RALGPS1 (ENSG00000136828), RASGEF1B (ENSG00000138670), RGL1 (ENSG00000143344), RASGEF1C (ENSG00000146090), RASGRP3 (ENSG00000152689), RAPGEF6 (ENSG00000158987), RGL4 (ENSG00000159496), RASGRP4 (ENSG00000171777), RASGRP1 (ENSG00000172575), RASGEF1A (ENSG00000198915), RGL3 (ENSG00000205517), RGL2 (ENSG00000237441)

Protein

Protein identifiers

Ral guanine nucleotide dissociation stimulator — Q12967 (reviewed: Q12967)

Alternative names: Ral guanine nucleotide exchange factor

All UniProt accessions (4): Q12967, A0A2R8YE90, A0A2R8YEX4, Q5T7U6

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a guanine nucleotide exchange factor (GEF) activating either RalA or RalB GTPases and plays an important role in intracellular transport. Interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap. During bacterial clearance, recognizes ‘Lys-33’-linked polyubiquitinated TRAF3 and subsequently mediates assembly of the exocyst complex.

Subunit / interactions. Interacts with RIT1 and RIT2. Interacts with OOG1. Interacts with TRAF3. Interacts with HRAS.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylation of Tyr-814 by MET blocks HRAS binding.

Domain organisation. The Ras-associating domain interacts with Ras.

Isoforms (6)

UniProt ID	Names	Canonical?
Q12967-1	1	yes
Q12967-2	2
Q12967-3	3
Q12967-4	4
Q12967-5	5
Q12967-6	6

RefSeq proteins (5): NP_001035827, NP_001258703, NP_001258704, NP_001258705, NP_006257* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR000651	Ras-like_Gua-exchang_fac_N	Domain
IPR001895	RASGEF_cat_dom	Domain
IPR008937	Ras-like_GEF	Family
IPR015758	RalGDS_RA	Domain
IPR019804	Ras_G-nucl-exch_fac_CS	Conserved_site
IPR023578	Ras_GEF_dom_sf	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036964	RASGEF_cat_dom_sf	Homologous_superfamily

Pfam: PF00617, PF00618, PF00788

UniProt features (33 total): strand 8, splice variant 5, compositionally biased region 4, domain 3, sequence conflict 3, helix 3, region of interest 3, chain 1, modified residue 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3KH0	X-RAY DIFFRACTION	2.1
1RAX	SOLUTION NMR
2B3A	SOLUTION NMR
2RGF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12967-F1	64.18	0.25

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 (1): 814

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-171007	p38MAPK events
R-HSA-5673001	RAF/MAP kinase cascade

MSigDB gene sets: 268 (showing top): TATTATA_MIR374, GTGCCTT_MIR506, NFKB_C, REACTOME_SIGNALLING_TO_RAS, RICKMAN_METASTASIS_DN, KEGG_PATHWAYS_IN_CANCER, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, REACTOME_SIGNALLING_TO_ERKS, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, REACTOME_P38MAPK_EVENTS, ZHU_CMV_ALL_DN, KEGG_COLORECTAL_CANCER, RYTTCCTG_ETS2_B

GO Biological Process (3): Ras protein signal transduction (GO:0007265), signal transduction (GO:0007165), small GTPase-mediated signal transduction (GO:0007264)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase regulator activity (GO:0030695), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), brush border (GO:0005903), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signalling to RAS	1
MAPK1/MAPK3 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
small GTPase-mediated signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
GTPase activity	1
nucleoside-triphosphatase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RALGDS	LRPAP1	P30533	996
RALGDS	RALA	P11233	988
RALGDS	RRAS	P10301	986
RALGDS	KRAS	P01116	981
RALGDS	RAP1A	P10113	979
RALGDS	RALB	P11234	953
RALGDS	HRAS	P01112	920
RALGDS	NRAS	P01111	846
RALGDS	RIN1	Q13671	826
RALGDS	AFDN	P55196	805
RALGDS	RAP2B	P17964	801
RALGDS	RALBP1	Q15311	784
RALGDS	SLCO6A1	Q86UG4	777
RALGDS	CNKSR1	Q969H4	777
RALGDS	ARAF	P07557	746

IntAct

38 interactions, top by confidence:

A	B	Type	Score
HRAS	RALGDS	psi-mi:“MI:0407”(direct interaction)	0.680
RALGDS	HRAS	psi-mi:“MI:2364”(proximity)	0.680
RALGDS	RAP1B	psi-mi:“MI:0915”(physical association)	0.570
RALGDS	BRAF	psi-mi:“MI:0915”(physical association)	0.550
RALGDS	BRAF	psi-mi:“MI:2364”(proximity)	0.550
BRAF	RALGDS	psi-mi:“MI:0915”(physical association)	0.550
RALGDS	CC2D2B	psi-mi:“MI:0915”(physical association)	0.400
RALGDS	RAP1A	psi-mi:“MI:0915”(physical association)	0.370
RALGDS	TP63	psi-mi:“MI:0915”(physical association)	0.370
RALGDS	Rit2	psi-mi:“MI:0915”(physical association)	0.370
RALGDS	RIT1	psi-mi:“MI:0915”(physical association)	0.370
CD68	RALGDS	psi-mi:“MI:0915”(physical association)	0.370
KRAS	RALGDS	psi-mi:“MI:0915”(physical association)	0.370
RRAS2	RALGDS	psi-mi:“MI:0915”(physical association)	0.370
RALGDS	CDH1	psi-mi:“MI:0914”(association)	0.350
RALGDS	CTNNB1	psi-mi:“MI:0914”(association)	0.350
RAF1	Ras	psi-mi:“MI:0914”(association)	0.350
FBXW7	RALGDS	psi-mi:“MI:2364”(proximity)	0.270
SPOP	RALGDS	psi-mi:“MI:2364”(proximity)	0.270
RALGDS	SPOP	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (63): RAP1A (Two-hybrid), RAP2A (Two-hybrid), RAP2B (Two-hybrid), HRAS (Two-hybrid), CNKSR1 (Affinity Capture-Western), RALGDS (Two-hybrid), RALGDS (Co-localization), HRAS (Co-localization), RALGDS (Two-hybrid), RALGDS (Two-hybrid), RALGDS (Affinity Capture-RNA), RAP2A (Reconstituted Complex), RALGDS (Affinity Capture-RNA), RALGDS (Two-hybrid), RALGDS (Affinity Capture-Western)

ESM2 similar proteins: A0A494C086, A0A494C0Z2, A0A494C191, A0JPH4, A6NHP3, A6NIY4, A6NJR5, A6NLX3, A6NNV3, A6QLI5, B0BNE4, O08918, O60543, O70302, O75916, P0CI01, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, P24864, P39949, P49805, Q12967, Q495Y7, Q495Y8, Q4VXA5, Q4ZIN3, Q5IBH6, Q5IBH7, Q5MJ70, Q5SYB0, Q5XIQ2, Q5ZJR9, Q61457, Q6AYG1

Diamond homologs: A2AR50, A2CEA7, B0M0P8, B0UXH6, F1M386, F1MSG6, F1PBJ0, O14827, P27671, P28818, P70392, Q03385, Q03386, Q07889, Q07890, Q12967, Q13905, Q13972, Q3MIN7, Q3UYI5, Q4R7W3, Q54FF3, Q54PQ4, Q54TK8, Q552M5, Q55GH9, Q5JS13, Q5ZJK0, Q60695, Q86G47, Q86X27, Q8CHG7, Q8IS14, Q8IS15, Q8IS16, Q8IS18, Q8IS20, Q8IS21, Q8SSQ0, Q8SSW7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RALGDS	“up-regulates activity”	RIT1	binding
RALGDS	“up-regulates activity”	RIN1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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
Signaling by high-kinase activity BRAF mutants	7	111.0×	5e-11
MAP2K and MAPK activation	7	99.9×	5e-11
Signaling by RAF1 mutants	7	97.5×	5e-11
Signaling by moderate kinase activity BRAF mutants	7	88.8×	6e-11
Paradoxical activation of RAF signaling by kinase inactive BRAF	7	88.8×	6e-11
Signaling downstream of RAS mutants	7	88.8×	6e-11
Negative regulation of MAPK pathway	5	66.4×	5e-07
Signaling by BRAF and RAF1 fusions	7	59.7×	9e-10

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	6	70.8×	7e-08
Ras protein signal transduction	5	48.9×	6e-06
MAPK cascade	6	43.8×	8e-07
positive regulation of ERK1 and ERK2 cascade	8	32.4×	4e-08
negative regulation of cell population proliferation	5	10.0×	2e-03
negative regulation of apoptotic process	6	9.9×	7e-04
positive regulation of gene expression	5	9.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	18
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

3538 predictions. Top by Δscore:

Variant	Effect	Δscore
9:133098758:CAGCT:C	acceptor_gain	1.0000
9:133098759:AGCT:A	acceptor_gain	1.0000
9:133098761:CT:C	acceptor_gain	1.0000
9:133098763:C:CC	acceptor_gain	1.0000
9:133098764:T:C	acceptor_loss	1.0000
9:133098766:G:GC	acceptor_gain	1.0000
9:133100262:A:AC	donor_gain	1.0000
9:133100263:C:CC	donor_gain	1.0000
9:133100265:TACTC:T	donor_loss	1.0000
9:133100266:A:AC	donor_gain	1.0000
9:133100266:ACT:A	donor_gain	1.0000
9:133100266:ACTC:A	donor_gain	1.0000
9:133100267:C:CA	donor_gain	1.0000
9:133100267:CT:C	donor_gain	1.0000
9:133100267:CTC:C	donor_gain	1.0000
9:133100267:CTCC:C	donor_gain	1.0000
9:133100267:CTCCG:C	donor_gain	1.0000
9:133100382:CCT:C	acceptor_loss	1.0000
9:133100383:CTG:C	acceptor_loss	1.0000
9:133100384:T:A	acceptor_loss	1.0000
9:133100389:C:CT	acceptor_gain	1.0000
9:133101514:GCTTA:G	donor_loss	1.0000
9:133101516:TTACC:T	donor_loss	1.0000
9:133101517:TACCA:T	donor_loss	1.0000
9:133101518:A:AC	donor_gain	1.0000
9:133101518:A:T	donor_loss	1.0000
9:133101519:C:CC	donor_gain	1.0000
9:133101519:C:CT	donor_loss	1.0000
9:133101763:C:CC	acceptor_gain	1.0000
9:133101934:TCACC:T	donor_loss	1.0000

AlphaMissense

5922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:133098693:A:G	L880P	1.000
9:133098693:A:T	L880H	1.000
9:133098699:A:G	F878S	1.000
9:133098726:G:T	A869D	1.000
9:133098730:A:C	Y868D	1.000
9:133098731:G:C	F867L	1.000
9:133098731:G:T	F867L	1.000
9:133098733:A:G	F867L	1.000
9:133098735:A:T	V866D	1.000
9:133098737:G:C	N865K	1.000
9:133098737:G:T	N865K	1.000
9:133100294:A:G	L848P	1.000
9:133100294:A:T	L848Q	1.000
9:133101563:A:T	V804D	1.000
9:133102869:A:G	L608P	1.000
9:133102872:A:G	L607P	1.000
9:133103766:G:T	A580D	1.000
9:133103784:A:G	L574P	1.000
9:133103793:A:G	L571P	1.000
9:133103803:C:G	G568R	1.000
9:133103811:G:T	P565H	1.000
9:133103814:A:T	V564D	1.000
9:133106725:G:C	F479L	1.000
9:133106725:G:T	F479L	1.000
9:133106727:A:G	F479L	1.000
9:133106728:G:C	N478K	1.000
9:133106728:G:T	N478K	1.000
9:133107187:G:C	F437L	1.000
9:133107187:G:T	F437L	1.000
9:133107189:A:G	F437L	1.000

dbSNP variants (sampled 300 via entrez): RS1000014603 (9:133129945 T>A), RS1000056068 (9:133136160 A>G), RS1000085967 (9:133099554 T>C), RS1000139305 (9:133114621 G>A), RS1000172332 (9:133114880 C>T), RS1000197779 (9:133100665 C>T), RS1000204269 (9:133114684 C>G,T), RS1000347967 (9:133116738 C>A,T), RS1000379319 (9:133131259 A>G,T), RS1000438165 (9:133127601 C>G,T), RS1000477276 (9:133115752 T>C), RS1000498596 (9:133131041 A>C,G), RS1000503844 (9:133101851 G>A), RS1000554802 (9:133097965 G>A,C), RS1000599346 (9:133103002 C>G)

Disease associations

OMIM: gene MIM:601619 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal recessive
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (3): hereditary breast ovarian cancer syndrome (MONDO:0003582), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009731_54	Blood protein levels in cardiovascular risk	2.000000e-78

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010600	angiopoietin-1 receptor measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance, increases expression (+1 more)	5
Cisplatin	affects expression, affects cotreatment, increases expression, decreases expression	3
Decitabine	affects expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression, affects cotreatment	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
Aflatoxin B1	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
Particulate Matter	increases abundance, increases expression	2
bufotalin	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
deguelin	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Antimycin A	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial