SRGAP1

Summary

SRGAP1 (SLIT-ROBO Rho GTPase activating protein 1, HGNC:17382) is a protein-coding gene on chromosome 12q14.2, encoding SLIT-ROBO Rho GTPase-activating protein 1 (Q7Z6B7). GTPase-activating protein for RhoA and Cdc42 small GTPases.

The protein encoded by this gene is a GTPase activator, working with the GTPase CDC42 to negatively regulate neuronal migration. The encoded protein interacts with the transmembrane receptor ROBO1 to inactivate CDC42.

Source: NCBI Gene 57522 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital anomaly of kidney and urinary tract (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 181 total — 1 pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_020762

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17382
Approved symbol	SRGAP1
Name	SLIT-ROBO Rho GTPase activating protein 1
Location	12q14.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1304, ARHGAP13
Ensembl gene	ENSG00000196935
Ensembl biotype	protein_coding
OMIM	606523
Entrez	57522

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 retained_intron, 4 protein_coding, 1 nonsense_mediated_decay

ENST00000355086, ENST00000537556, ENST00000537585, ENST00000542381, ENST00000542841, ENST00000543397, ENST00000631006, ENST00000695902, ENST00000875665, ENST00000875666

RefSeq mRNA: 2 — MANE Select: NM_020762 NM_001346201, NM_020762

CCDS: CCDS8967, CCDS91718

Canonical transcript exons

ENST00000355086 — 22 exons

Exon	Start	End
ENSE00000799611	64108932	64109037
ENSE00000920599	64091276	64091378
ENSE00000920600	64094932	64094992
ENSE00000920604	64097241	64097375
ENSE00000920607	64111762	64111986
ENSE00000920608	64115814	64115893
ENSE00000920610	64125977	64126157
ENSE00000920612	64127590	64127724
ENSE00000920615	64127861	64128200
ENSE00001100765	64080286	64080370
ENSE00001177193	64086999	64087026
ENSE00001177205	64142295	64162217
ENSE00001733453	64095127	64095204
ENSE00002278180	63844700	63844883
ENSE00003459886	63989910	63990072
ENSE00003477549	64065118	64065219
ENSE00003492668	64016950	64017012
ENSE00003514340	64042790	64042972
ENSE00003545487	64062917	64063138
ENSE00003590086	64043447	64043575
ENSE00003625452	64078919	64079116
ENSE00003765156	63983947	63984142

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 95.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1999 / max 287.0723, expressed in 1398 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126421	3.4245	1064
126430	1.0275	274
126420	0.8826	536
126422	0.8654	485

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	95.27	gold quality
cortical plate	UBERON:0005343	94.53	gold quality
medial globus pallidus	UBERON:0002477	90.70	gold quality
lateral globus pallidus	UBERON:0002476	90.46	gold quality
globus pallidus	UBERON:0001875	90.36	gold quality
cartilage tissue	UBERON:0002418	90.32	gold quality
secondary oocyte	CL:0000655	90.31	gold quality
epithelial cell of pancreas	CL:0000083	90.28	silver quality
pancreatic ductal cell	CL:0002079	89.91	gold quality
ventral tegmental area	UBERON:0002691	88.90	gold quality
kidney epithelium	UBERON:0004819	88.03	silver quality
sural nerve	UBERON:0015488	87.78	gold quality
ganglionic eminence	UBERON:0004023	87.41	gold quality
nasal cavity epithelium	UBERON:0005384	86.92	silver quality
dorsal root ganglion	UBERON:0000044	86.45	gold quality
inferior vagus X ganglion	UBERON:0005363	86.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.19	gold quality
medulla oblongata	UBERON:0001896	85.79	gold quality
dorsal plus ventral thalamus	UBERON:0001897	85.65	gold quality
subthalamic nucleus	UBERON:0001906	85.13	gold quality
pericardium	UBERON:0002407	85.11	gold quality
trachea	UBERON:0003126	85.06	gold quality
germinal epithelium of ovary	UBERON:0001304	85.00	gold quality
trigeminal ganglion	UBERON:0001675	84.78	gold quality
superior vestibular nucleus	UBERON:0007227	84.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.60	gold quality
lower lobe of lung	UBERON:0008949	84.23	gold quality
renal medulla	UBERON:0000362	84.22	gold quality
stromal cell of endometrium	CL:0002255	84.04	gold quality
substantia nigra pars reticulata	UBERON:0001966	83.85	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	47.27
E-CURD-119	yes	31.51
E-HCAD-10	yes	18.76
E-MTAB-8271	yes	15.01
E-ANND-3	yes	10.55
E-CURD-114	yes	7.83

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 12)

• FNBP2, ARHGAP13, ARHGAP14 and ARHGAP4 constitute the FNBP2 family characterized by FCH, RhoGAP and SH3 domains. (PMID:12736724)
• This study proposed that the expression of SRGAP1 in the anterior neocortex may mark the early location of the human motor cortex, including its corticospinal projection neurons, allowing further study of their early differentiation. (PMID:21060114)
• genome-wide linkage analysis in populations in Ohio and Poland: Data suggest that missense mutations in SRGAP1 are associated with genetic predisposition to papillary thyroid carcinoma. (PMID:23539728)
• Data indicate that srGAP1 possesses a GAP activity specific to Rac1 and is recruited to lamellipodia in a Rac1-dependent manner. (PMID:24006490)
• we identified a consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P(meta) = 1.14 x 10(-7)) (PMID:25134534)
• The interaction of betaPix with srGAP1 is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration. (PMID:25150978)
• The elevated miR-145 present in invasive glioblastoma cells (IM3 cells) targets and down-regulated srGAP1, thereby allowing downstream G-proteins to remain in their active state and promote the observed invasive phenotype (PMID:26026080)
• Mutations of the SLIT2-ROBO2 pathway genes SLIT2 and SRGAP1 confer risk for congenital anomalies of the kidney and urinary tract (PMID:26026792)
• Results show that the protein expression of srGAP1 is remarkably decreased in 47.5% of colorectal cancer (CRC) tissues compared and is found to be associated with tumor progression and poor prognosis. (PMID:27923383)
• the RhoA antagonist, SRGAP1, is present at subconfluent junctions to a greater extent than in confluent cultures and SRGAP1 RNAi restores RhoA signaling and contractility in subconfluent cultures to levels seen in confluent cells. (PMID:29160905)
• High SRGAP1 expression is associated with gastric tumorigenesis. (PMID:29234151)
• Identification of SRGAP2 as a potential oncogene and a prognostic biomarker in hepatocellular carcinoma. (PMID:33984363)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	srgap1a	ENSDARG00000007461
mus_musculus	Srgap1	ENSMUSG00000020121
rattus_norvegicus	Srgap1	ENSRNOG00000004603
caenorhabditis_elegans		WBGENE00006406

Paralogs (5): ARHGAP4 (ENSG00000089820), SRGAP2C (ENSG00000171943), SRGAP3 (ENSG00000196220), SRGAP2B (ENSG00000196369), SRGAP2 (ENSG00000266028)

Protein

Protein identifiers

SLIT-ROBO Rho GTPase-activating protein 1 — Q7Z6B7 (reviewed: Q7Z6B7)

Alternative names: Rho GTPase-activating protein 13

All UniProt accessions (3): A0A8Q3WKV0, Q7Z6B7, G5EA48

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein for RhoA and Cdc42 small GTPases. Together with CDC42 seems to be involved in the pathway mediating the repulsive signaling of Robo and Slit proteins in neuronal migration. SLIT2, probably through interaction with ROBO1, increases the interaction of SRGAP1 with ROBO1 and inactivates CDC42.

Subunit / interactions. Homodimer. Forms a heterooligomer with SRGAP2 and SRGAP3 through its F-BAR domain. Interacts with ROBO1, CDC42 and RHOA. Interacts with FASLG.

Tissue specificity. Expressed in brain, lung, kidney, and testis.

Disease relevance. Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470] A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. The F-BAR domain mediates oligomerization, binds membranes, and constrains plasma membrane protrusions.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z6B7-1	1	yes
Q7Z6B7-2	2

RefSeq proteins (2): NP_001333130, NP_065813* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001060	FCH_dom	Domain
IPR001452	SH3_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR031160	F_BAR_dom	Domain
IPR035648	srGAP1/2/3_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR037451	srGAP1_F-BAR	Domain
IPR051627	SLIT-ROBO_RhoGAP	Family

Pfam: PF00018, PF00611, PF00620

UniProt features (29 total): modified residue 7, compositionally biased region 5, sequence variant 5, region of interest 4, domain 3, coiled-coil region 2, chain 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6B7-F1	73.49	0.49

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): 542 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (7): 416, 835, 917, 932, 999, 1001, 1032

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-428543	Inactivation of CDC42 and RAC1
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-376176	Signaling by ROBO receptors
R-HSA-422475	Axon guidance
R-HSA-9012999	RHO GTPase cycle
R-HSA-9675108	Nervous system development
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 210 (showing top): GOBP_SYNAPSE_ASSEMBLY, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGCATT_MIR365, GOBP_CELL_JUNCTION_ORGANIZATION, WANG_LMO4_TARGETS_DN, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, GATA6_01, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, RIGGI_EWING_SARCOMA_PROGENITOR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY

GO Biological Process (6): Rho protein signal transduction (GO:0007266), nervous system development (GO:0007399), cell migration (GO:0016477), negative regulation of cell migration (GO:0030336), regulation of synapse assembly (GO:0051963), signal transduction (GO:0007165)

GO Molecular Function (3): GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by ROBO receptors	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Axon guidance	1
Nervous system development	1
Signaling by Rho GTPases	1
Developmental Biology	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
small GTPase-mediated signal transduction	1
system development	1
cell motility	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
synapse assembly	1
regulation of synapse organization	1
regulation of cell junction assembly	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
GTPase binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRGAP1	ROBO1	Q9Y6N7	992
SRGAP1	SLIT3	O75094	921
SRGAP1	CDC42	P21181	876
SRGAP1	SLIT1	O75093	836
SRGAP1	WASF1	Q92558	756
SRGAP1	ROBO2	Q9HCK4	653
SRGAP1	SLIT2	O94813	650
SRGAP1	RHOA	P06749	623
SRGAP1	TRIP10	Q15642	622
SRGAP1	ARHGEF7	Q14155	559
SRGAP1	HABP2	Q14520	535
SRGAP1	FOXE1	O00358	516
SRGAP1	FNBP1	Q96RU3	482
SRGAP1	PLXNA1	Q9UIW2	479
SRGAP1	FNBP1L	Q5T0N5	452

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SRGAP1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.740
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
ARHGEF7	CDC42	psi-mi:“MI:0914”(association)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
ARHGEF7	SRGAP1	psi-mi:“MI:0915”(physical association)	0.500
ARHGEF7	PPP2R1A	psi-mi:“MI:0914”(association)	0.500
	SRGAP1	psi-mi:“MI:0407”(direct interaction)	0.440
SRGAP1	CD9	psi-mi:“MI:0915”(physical association)	0.400
FASLG	SRGAP1	psi-mi:“MI:0915”(physical association)	0.400
SRGAP1	HTT	psi-mi:“MI:0915”(physical association)	0.370
HTT	SRGAP1	psi-mi:“MI:0915”(physical association)	0.370
SKA1	ILVBL	psi-mi:“MI:0914”(association)	0.350
Actb		psi-mi:“MI:0914”(association)	0.350
CDK8	CCNC	psi-mi:“MI:0914”(association)	0.350
RAD18	SRGAP3	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
ARHGEF10L	MCM7	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350

BioGRID (49): SRGAP1 (Affinity Capture-MS), SRGAP1 (Affinity Capture-MS), SRGAP1 (Affinity Capture-MS), SRGAP1 (Affinity Capture-MS), SRGAP1 (Affinity Capture-RNA), SRGAP1 (Affinity Capture-MS), SRGAP1 (Affinity Capture-RNA), SRGAP1 (Affinity Capture-MS), SRGAP1 (Proximity Label-MS), SRGAP1 (Affinity Capture-Western), SRGAP1 (FRET), SRGAP1 (Affinity Capture-MS), ARHGAP1 (Affinity Capture-MS), ARHGEF19 (Affinity Capture-MS), NKTR (Affinity Capture-MS)

ESM2 similar proteins: A1XBS5, B0S6J3, D4A208, O35180, O35964, O43295, O75044, P0DJJ0, P0DMP2, P25343, Q08DK5, Q15057, Q1LU86, Q1RMK1, Q2VR06, Q32LM0, Q3SZG6, Q3V2J0, Q5AFE4, Q5FVC7, Q5PPJ9, Q5PPZ5, Q5R8P5, Q5ZIR1, Q5ZJ81, Q5ZK62, Q62419, Q62421, Q68FW8, Q6AYE2, Q6GN09, Q6IVG4, Q6ZQK5, Q6ZTR7, Q7Z6B7, Q812A2, Q8AXU9, Q8BP22, Q8I190, Q8I1C0

Diamond homologs: A0A0G2JTR4, A1A4S6, A2RUV4, A4II46, A6NI28, A6QNS3, A6X8Z5, A8WRJ2, B2RQE8, B5DFQ4, D3ZZN9, E7EZG2, E7F3F0, F1LQX4, F1LXF1, O14014, O14559, O43182, O43295, O54834, O60890, O94466, P0CAX5, P11274, P15882, P30337, P34288, P38339, P39960, P46941, P52757, P81128, P83509, P97393, Q03070, Q08DP6, Q12979, Q13017, Q17QN0, Q17R89

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SRGAP1	“down-regulates activity”	RAC1	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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
Activation of BAD and translocation to mitochondria	6	134.3×	4e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	118.5×	4e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	118.5×	4e-10
Activation of BH3-only proteins	6	87.6×	2e-09
RHO GTPases activate PKNs	6	56.0×	3e-08
Intrinsic Pathway for Apoptosis	6	51.7×	4e-08
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	36.3×	2e-09
G2/M Checkpoints	8	31.6×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	50.9×	8e-06
intracellular protein localization	7	20.4×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	119
Likely benign	24
Benign	12

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
208457	NM_020762.4(SRGAP1):c.823G>A (p.Ala275Thr)	Pathogenic

SpliceAI

4758 predictions. Top by Δscore:

Variant	Effect	Δscore
12:63845857:C:G	donor_gain	1.0000
12:63963180:T:G	donor_gain	1.0000
12:63983942:CTTA:C	acceptor_loss	1.0000
12:63983943:TTAG:T	acceptor_loss	1.0000
12:63983944:TAG:T	acceptor_loss	1.0000
12:63983945:A:AC	acceptor_loss	1.0000
12:63983945:A:AG	acceptor_gain	1.0000
12:63983946:G:GA	acceptor_gain	1.0000
12:63983946:GA:G	acceptor_gain	1.0000
12:63983946:GAA:G	acceptor_gain	1.0000
12:63983946:GAAA:G	acceptor_gain	1.0000
12:63983946:GAAAT:G	acceptor_gain	1.0000
12:63984138:TACAA:T	donor_gain	1.0000
12:63984140:CAA:C	donor_gain	1.0000
12:63984141:AA:A	donor_gain	1.0000
12:63984141:AAG:A	donor_loss	1.0000
12:63984142:AG:A	donor_loss	1.0000
12:63984143:G:GG	donor_gain	1.0000
12:63984143:GTAAG:G	donor_loss	1.0000
12:63984144:T:G	donor_loss	1.0000
12:63989907:TAGG:T	acceptor_loss	1.0000
12:63989908:A:AG	acceptor_gain	1.0000
12:63989909:G:GA	acceptor_loss	1.0000
12:63989909:G:GG	acceptor_gain	1.0000
12:63989909:GGAA:G	acceptor_gain	1.0000
12:63989909:GGAAA:G	acceptor_gain	1.0000
12:63990040:A:G	donor_gain	1.0000
12:63990060:G:GT	donor_gain	1.0000
12:64016942:A:AG	acceptor_gain	1.0000
12:64016943:A:G	acceptor_gain	1.0000

AlphaMissense

7245 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:63984013:T:C	L45P	1.000
12:63984016:T:C	L46P	1.000
12:63984025:T:C	L49P	1.000
12:63984040:G:C	R54P	1.000
12:63984048:G:C	A57P	1.000
12:63984079:T:C	L67P	1.000
12:63989944:T:A	W100R	1.000
12:63989944:T:C	W100R	1.000
12:63989957:T:C	L104P	1.000
12:64042845:T:C	L182P	1.000
12:64043489:G:C	A239P	1.000
12:64043493:G:C	R240P	1.000
12:64062945:T:C	L277P	1.000
12:64062957:T:C	L281P	1.000
12:64062969:T:C	L285P	1.000
12:64062974:G:C	A287P	1.000
12:64062987:T:C	L291P	1.000
12:64078937:G:C	A382P	1.000
12:64079105:T:C	F438L	1.000
12:64079107:C:A	F438L	1.000
12:64079107:C:G	F438L	1.000
12:64080329:T:C	L456P	1.000
12:64097301:T:C	L580P	1.000
12:64126001:C:A	A750D	1.000
12:64126061:T:C	L770P	1.000
12:64126090:T:A	W780R	1.000
12:64126090:T:C	W780R	1.000
12:64126093:T:A	W781R	1.000
12:64126093:T:C	W781R	1.000
12:64126099:G:C	G783R	1.000

dbSNP variants (sampled 300 via entrez): RS1000015885 (12:63910445 A>T), RS1000053933 (12:63993086 G>A), RS1000055800 (12:63999381 G>A), RS1000064172 (12:64098435 C>T), RS1000093962 (12:64139528 A>G), RS1000108208 (12:64000061 G>A,C), RS1000108707 (12:64092452 A>G), RS1000112810 (12:63983218 A>C), RS1000113987 (12:64051688 T>G), RS1000117166 (12:64138808 A>G), RS1000122463 (12:63991685 G>A), RS1000124567 (12:64078270 A>C), RS1000130581 (12:63870864 G>A), RS1000136384 (12:63914063 A>G), RS1000142663 (12:63901425 G>A)

Disease associations

OMIM: gene MIM:606523 | disease phenotypes: MIM:188470, MIM:256100, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital anomaly of kidney and urinary tract	Moderate	Autosomal dominant
thyroid cancer, nonmedullary, 2	No Known Disease Relationship	Autosomal dominant

Mondo (4): thyroid cancer, nonmedullary, 2 (MONDO:0008566), nephronophthisis (MONDO:0019005), congenital anomaly of kidney and urinary tract (MONDO:0019719), congenital anomalies of kidney and urinary tract 1 (MONDO:0012561)

Orphanet (2): Nephronophthisis (Orphanet:655), Renal or urinary tract malformation (Orphanet:93545)

HPO phenotypes

5 total (6 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0002895	Papillary thyroid carcinoma
HP:0006731	Follicular thyroid carcinoma
HP:0040198	Non-medullary thyroid carcinoma
HP:0000090	Nephronophthisis

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002576_2	Epithelial ovarian cancer	1.000000e-07
GCST004400_2	Bone erosion in rheumatoid arthritis	4.000000e-06
GCST008275_3	Cerebral microbleeds	3.000000e-06
GCST010320_4	PR interval	7.000000e-11
GCST010321_73	PR interval	1.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005413	joint damage measurement
EFO:0010059	cerebral microbleeds
EFO:0004462	PR interval

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C566906	Cakut (supp.)
C563661	Renal Hypodysplasia, Nonsyndromic, 1 (supp.)
C572845	Thyroid cancer, follicular (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
trichostatin A	increases expression, affects cotreatment	3
Cisplatin	affects cotreatment, decreases expression	3
Arsenic	affects methylation, increases abundance, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
sodium arsenate	increases abundance, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
prothioconazole	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02021006	PHASE3	UNKNOWN	Antibiotic Prophylaxis and Renal Damage In Congenital Abnormalities of the Kidney and Urinary Tract
NCT04544111	PHASE2	ACTIVE_NOT_RECRUITING	PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer
NCT04462471	PHASE1	COMPLETED	Vemurafenib Plus Copanlisib in Radioiodine-Refractory (RAIR) Thyroid Cancers
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
NCT05796960	Not specified	UNKNOWN	European Multicenter Study on Surgical Management of Advanced Thyroid Cancer
NCT06730321	Not specified	RECRUITING	Surgical Competency for Robot-Assisted Thyroidectomy: Construction and Validation of a Robotic Thyroidectomy Assessment Score (RTAS)
NCT07122557	Not specified	NOT_YET_RECRUITING	Real World Effectiveness of Bictegravir/Emtricitabine/Tenofovir Alafenamide(BIC/FTC/TAF) in PLWH in Precarity Settings in France -IMEA073
NCT04537364	Not specified	COMPLETED	Prediction of Renal Parenchymal Damage of CAKUT
NCT06921733	Not specified	RECRUITING	Ultrasound Localization Microscopy in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
NCT01022957	Not specified	COMPLETED	Nephronophthisis : Clinical and Genetic Study
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05286632	Not specified	COMPLETED	KidneYou - Innovative Digital Therapy
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06648044	Not specified	RECRUITING	Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies
NCT00925379	Not specified	COMPLETED	Renal HYPODYSPLASIA : Genetic and Familial Assessment