SHROOM3

Summary

SHROOM3 (shroom family member 3, HGNC:30422) is a protein-coding gene on chromosome 4q21.1, encoding Protein Shroom3 (Q8TF72). Controls cell shape changes in the neuroepithelium during neural tube closure.

This gene encodes a PDZ-domain-containing protein that belongs to a family of Shroom-related proteins. This protein may be involved in regulating cell shape in certain tissues. A similar protein in mice is required for proper neurulation.

Source: NCBI Gene 57619 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neural tube defect (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 65
• Clinical variants (ClinVar): 433 total
• Druggable target: yes
• MANE Select transcript: NM_020859

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30422
Approved symbol	SHROOM3
Name	shroom family member 3
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ShrmL, SHRM, KIAA1481, APXL3
Ensembl gene	ENSG00000138771
Ensembl biotype	protein_coding
OMIM	604570
Entrez	57619

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding_CDS_not_defined, 4 protein_coding, 1 retained_intron

ENST00000296043, ENST00000425645, ENST00000466541, ENST00000469923, ENST00000473602, ENST00000481002, ENST00000484236, ENST00000485780, ENST00000486758, ENST00000490690, ENST00000497440, ENST00000644244, ENST00000646790, ENST00000912766

RefSeq mRNA: 1 — MANE Select: NM_020859 NM_020859

CCDS: CCDS3579

Canonical transcript exons

ENST00000296043 — 11 exons

Exon	Start	End
ENSE00001077911	76756449	76756937
ENSE00001077914	76759545	76759695
ENSE00001077917	76770626	76770898
ENSE00001140439	76754311	76755192
ENSE00001277290	76738761	76741926
ENSE00001277303	76435229	76436220
ENSE00001824822	76778809	76783253
ENSE00003460547	76710156	76710287
ENSE00003481170	76749017	76749090
ENSE00003499008	76730804	76730935
ENSE00003591533	76555609	76555763

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4624 / max 461.9605, expressed in 1231 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48349	4.6497	718
48357	3.1588	944
48362	1.3722	265
48336	0.7847	279
48341	0.5977	157
48352	0.4237	148
48348	0.4169	130
48333	0.3060	117
48340	0.2939	111
48342	0.2143	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.38	gold quality
epithelial cell of pancreas	CL:0000083	96.62	gold quality
pancreatic ductal cell	CL:0002079	95.03	gold quality
bronchial epithelial cell	CL:0002328	94.70	gold quality
ventricular zone	UBERON:0003053	94.60	gold quality
corpus epididymis	UBERON:0004359	94.44	gold quality
bronchus	UBERON:0002185	93.91	gold quality
esophagus squamous epithelium	UBERON:0006920	93.86	gold quality
pigmented layer of retina	UBERON:0001782	93.72	gold quality
sural nerve	UBERON:0015488	93.35	gold quality
colonic mucosa	UBERON:0000317	93.34	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.99	gold quality
saphenous vein	UBERON:0007318	92.24	gold quality
epithelium of mammary gland	UBERON:0003244	90.44	gold quality
mammary duct	UBERON:0001765	90.37	gold quality
duodenum	UBERON:0002114	90.12	gold quality
lower lobe of lung	UBERON:0008949	90.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.77	gold quality
jejunal mucosa	UBERON:0000399	89.63	gold quality
kidney epithelium	UBERON:0004819	89.43	gold quality
gall bladder	UBERON:0002110	89.14	gold quality
parotid gland	UBERON:0001831	89.05	gold quality
rectum	UBERON:0001052	88.67	gold quality
germinal epithelium of ovary	UBERON:0001304	88.51	gold quality
epithelium of nasopharynx	UBERON:0001951	88.36	gold quality
nasal cavity epithelium	UBERON:0005384	88.36	silver quality
thoracic aorta	UBERON:0001515	88.05	gold quality
eye	UBERON:0000970	88.04	gold quality
descending thoracic aorta	UBERON:0002345	88.02	gold quality
ascending aorta	UBERON:0001496	87.89	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	3660.51
E-MTAB-7303	no	194.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PITX1

miRNA regulators (miRDB)

157 targeting SHROOM3, 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-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 10)

• A recessive missense mutation in SHROOM3 is associated with heterotaxy syndrome. (PMID:21936905)
• RESULTS: rs1260326 in GCKR (beta=1.30, P = 3.23E-03), rs17319721 in SHROOM3 (beta = -1.28, P-value = 3.18E-03) and rs12917707 in UMOD (beta = 2.0, P-value = 8.84E-04) were significantly associated with baseline estimated GFR (PMID:23586973)
• variants disrupting the actin-binding domain of SHROOM3 may cause podocyte effacement and impairment of the glomerular filtration barrier (PMID:25273069)
• The SNP rs17319721 functions as a cis-acting expression quantitative trait locus of SHROOM3 that facilitates TGF-B1 signaling and contributes to allograft injury. (PMID:25437874)
• Two protein-truncating de novo mutations in two independent cases in SHROOM3 strongly implicates this protein in severe human neural tube defects. (PMID:25805808)
• Functional variants were further confirmed by western blot and the mammalian two-hybrid assays. Loss of function (LoF) variants were identified in SHROOM3. We observed 1.56 times as many rare [minor allele frequency (MAF) < 0.01] coding variants (p = 2.9 x 10(-3)) in SHROOM genes, and 4.5 times as many rare D-Mis (deleterious missense) variants in SHROOM2 genes in the Neural tube defects cases compared with the controls (PMID:29423651)
• We determined that coding variant P1244L attenuates the interaction of SHROOM3 with 14-3-3, suggesting alterations to the Hippo pathway, a known mediator of CKD. (PMID:29476007)
• We confirmed the interaction of endogenous SHROOM3 with FYN in podocytes via a critical Src homology 3-binding domain, distinct from its ROCK-binding domain. Shroom3-Fyn interaction was required in vitro and in vivo for activation of Fyn kinase and downstream nephrin phosphorylation in podocytes. (PMID:30341149)
• The three genes associated with chronic kidney disease (AGT, GLO1, and SHROOM3) showed associations with both the high levels of oxidatively damaged DNA and genomic instability. (PMID:32265040)
• A homozygous pathogenic variant in SHROOM3 associated with anencephaly and cleft lip and palate. (PMID:32621286)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	shroom3	ENSDARG00000102180
mus_musculus	Shroom3	ENSMUSG00000029381
rattus_norvegicus	Shroom3	ENSRNOG00000002208
drosophila_melanogaster	Shrm	FBGN0085408

Paralogs (3): SHROOM2 (ENSG00000146950), SHROOM4 (ENSG00000158352), SHROOM1 (ENSG00000164403)

Protein

Protein identifiers

Protein Shroom3 — Q8TF72 (reviewed: Q8TF72)

Alternative names: Shroom-related protein

All UniProt accessions (3): A0A2R8Y5P9, A0A2R8Y7T7, Q8TF72

UniProt curated annotations — full annotation on UniProt →

Function. Controls cell shape changes in the neuroepithelium during neural tube closure. Induces apical constriction in epithelial cells by promoting the apical accumulation of F-actin and myosin II, and probably by bundling stress fibers. Induces apicobasal cell elongation by redistributing gamma-tubulin and directing the assembly of robust apicobasal microtubule arrays.

Subunit / interactions. Interacts with F-actin. Interacts with ROCK1.

Subcellular location. Cell junction. Adherens junction. Cytoplasm. Cytoskeleton. Apical cell membrane.

Domain organisation. The ASD1 domain mediates F-actin binding. The ASD2 domain mediates the interaction with ROCK1 and is required for apical constriction induction.

Similarity. Belongs to the shroom family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TF72-1	1	yes
Q8TF72-2	2

RefSeq proteins (1): NP_065910* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR014799	ASD2_dom	Domain
IPR014800	ASD1_dom	Domain
IPR027685	Shroom_fam	Family
IPR036034	PDZ_sf	Homologous_superfamily

Pfam: PF00595, PF08687, PF08688

UniProt features (53 total): compositionally biased region 18, modified residue 12, region of interest 10, splice variant 4, sequence variant 4, domain 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6FBB	X-RAY DIFFRACTION	1.3
6FCP	X-RAY DIFFRACTION	1.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF72-F1	44.41	0.10

Functional residue map

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

Post-translational modifications (12): 213, 439, 443, 816, 890, 910, 913, 970, 1069, 1072, 1221, 1441

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GOBP_APICAL_PROTEIN_LOCALIZATION, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CELLULAR_PIGMENTATION, GOBP_PIGMENTATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_ACTIN_FILAMENT_ORGANIZATION, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, GGCAGTG_MIR3243P, GOCC_APICAL_PLASMA_MEMBRANE, AIGNER_ZEB1_TARGETS, GOMF_ACTIN_BINDING, CUI_TCF21_TARGETS_2_DN

GO Biological Process (6): cell morphogenesis (GO:0000902), actin filament organization (GO:0007015), pattern specification process (GO:0007389), regulation of cell shape (GO:0008360), cellular pigment accumulation (GO:0043482), apical protein localization (GO:0045176)

GO Molecular Function (3): actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (10): cytoskeleton (GO:0005856), microtubule (GO:0005874), adherens junction (GO:0005912), apical plasma membrane (GO:0016324), cortical actin cytoskeleton (GO:0030864), apical junction complex (GO:0043296), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell junction	2
cellular anatomical structure	2
anatomical structure morphogenesis	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
multicellular organism development	1
multicellular organismal process	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cellular pigmentation	1
pigment accumulation	1
cellular response to stimulus	1
intracellular protein localization	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
apical part of cell	1
plasma membrane region	1
actin cytoskeleton	1
cortical cytoskeleton	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

1768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHROOM3	MYH10	P35580	722
SHROOM3	NECTIN3	Q9NQS3	711
SHROOM3	AFG2B	Q9BVQ7	630
SHROOM3	UMOD	P07911	612
SHROOM3	CELSR1	Q9NYQ6	604
SHROOM3	ROCK1	Q13464	598
SHROOM3	TJP1	Q07157	564
SHROOM3	APEX1	P27695	543
SHROOM3	DCDC1	P59894	525
SHROOM3	CDH2	P19022	518
SHROOM3	SLC7A9	P82251	507
SHROOM3	MAP3K13	O43283	474
SHROOM3	MAP3K12	Q12852	454
SHROOM3	APOL1	O14791	436
SHROOM3	SLC34A1	Q06495	424

IntAct

209 interactions, top by confidence:

A	B	Type	Score
RPS6KA2	MAPK1	psi-mi:“MI:0914”(association)	0.910
CDK2	CCNB1	psi-mi:“MI:0914”(association)	0.890
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
AQP7	PLIN1	psi-mi:“MI:0914”(association)	0.570
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
VASP	SHROOM3	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
SLC15A5	SHROOM3	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
MAST2	SHROOM3	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
NHERF4	SHROOM3	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SNX27	SHROOM3	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	SHROOM3	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
SHROOM3	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (98): SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SHROOM3 (Proximity Label-MS), SHROOM3 (Affinity Capture-RNA), SHROOM3 (Affinity Capture-RNA), SHROOM3 (Affinity Capture-MS)

ESM2 similar proteins: A2A7S8, A5D7K1, A5PK23, B1AXH1, F1QGH6, O94885, O95402, Q08495, Q08DM1, Q3T044, Q499V8, Q5HYW2, Q5PQP4, Q5R4B6, Q5R8Q8, Q5SYE7, Q5T0Z8, Q5U2R6, Q6PDH0, Q6PFX7, Q6PGN9, Q6ZVC0, Q7TT28, Q80U35, Q80VC9, Q80Z38, Q86UU1, Q86WR7, Q8BI29, Q8C5R2, Q8CAF4, Q8JZX9, Q8K4J6, Q8N1G1, Q8TF72, Q91Z58, Q969V6, Q96A73, Q9BW04, Q9D0P7

Diamond homologs: A1Z9P3, Q09JY9, Q13796, Q1W617, Q7TP36, Q8TF72, Q9QXN0, Q9ULL8, A1ZA47, A2ALU4, A5H447, D4A702, E1BKA3, O00151, O14639, O43294, O60711, O70209, O70400, O75112, O94929, P20271, P48059, P49023, P49024, P50464, P52944, Q09476, Q0WSN2, Q15942, Q1JQB5, Q2KJ33, Q2TCH4, Q2YDK0, Q3MHZ4, Q3SX26, Q3SX40, Q3SYZ8, Q3T0X8, Q3TJD7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 155 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	50.7×	6e-10
Activation of BAD and translocation to mitochondria	7	50.3×	2e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	44.4×	6e-09
Activation of BH3-only proteins	7	32.8×	5e-08
RHO GTPases activate PKNs	9	26.9×	2e-09
Ras activation upon Ca2+ influx through NMDA receptor	5	26.9×	2e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	25.6×	3e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	25.6×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	45.0×	3e-13
protein localization to synapse	6	32.4×	6e-06
receptor clustering	7	30.8×	1e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	6	20.9×	4e-05
protein targeting	7	18.1×	2e-05
establishment of cell polarity	5	13.5×	2e-03
intracellular protein localization	11	8.1×	2e-05
protein-containing complex assembly	10	8.0×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	304
Likely benign	64
Benign	39

Top pathogenic / likely-pathogenic (0)

SpliceAI

4154 predictions. Top by Δscore:

Variant	Effect	Δscore
4:76555759:CGCAG:C	donor_loss	1.0000
4:76555760:GCAGG:G	donor_loss	1.0000
4:76555761:CAGGT:C	donor_loss	1.0000
4:76555762:AGG:A	donor_loss	1.0000
4:76555763:GGTA:G	donor_loss	1.0000
4:76555764:G:A	donor_loss	1.0000
4:76555765:T:A	donor_loss	1.0000
4:76710155:GAGAT:G	acceptor_gain	1.0000
4:76749014:AAG:A	acceptor_gain	1.0000
4:76749015:A:G	acceptor_gain	1.0000
4:76759537:T:TA	acceptor_gain	1.0000
4:76759692:GAAG:G	donor_gain	1.0000
4:76759694:AGGT:A	donor_loss	1.0000
4:76759695:GGTAA:G	donor_loss	1.0000
4:76759696:G:A	donor_loss	1.0000
4:76759697:T:A	donor_loss	1.0000
4:76769526:T:G	donor_gain	1.0000
4:76770620:TTTCA:T	acceptor_loss	1.0000
4:76770621:TTCA:T	acceptor_loss	1.0000
4:76770622:TCA:T	acceptor_loss	1.0000
4:76770623:CA:C	acceptor_loss	1.0000
4:76770624:A:C	acceptor_loss	1.0000
4:76770624:AGGCT:A	acceptor_gain	1.0000
4:76770625:GGCTG:G	acceptor_gain	1.0000
4:76778994:G:GT	donor_gain	1.0000
4:76448355:T:G	acceptor_gain	0.9900
4:76448356:A:AG	acceptor_gain	0.9900
4:76448357:C:G	acceptor_gain	0.9900
4:76513263:GC:G	donor_gain	0.9900
4:76551528:T:TA	donor_gain	0.9900

AlphaMissense

12981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:76436171:T:C	F40S	0.999
4:76778867:T:C	L1894P	0.999
4:76436164:T:A	W38R	0.998
4:76436164:T:C	W38R	0.998
4:76770633:T:C	L1786P	0.998
4:76770816:T:C	L1847P	0.998
4:76778993:G:C	R1936P	0.998
4:76436166:G:C	W38C	0.997
4:76436166:G:T	W38C	0.997
4:76436170:T:C	F40L	0.997
4:76436172:T:A	F40L	0.997
4:76436172:T:G	F40L	0.997
4:76770828:T:C	L1851P	0.997
4:76770846:G:C	R1857P	0.997
4:76779041:T:C	L1952P	0.997
4:76555745:T:C	L102P	0.996
4:76770776:T:G	Y1834D	0.996
4:76770785:T:C	F1837L	0.996
4:76770787:C:A	F1837L	0.996
4:76770787:C:G	F1837L	0.996
4:76770795:A:C	D1840A	0.996
4:76770795:A:T	D1840V	0.996
4:76770819:T:C	L1848P	0.996
4:76770837:G:C	R1854P	0.996
4:76770840:T:C	L1855P	0.996
4:76778857:G:C	A1891P	0.996
4:76778889:G:C	R1901S	0.996
4:76778889:G:T	R1901S	0.996
4:76436207:T:C	L52S	0.995
4:76756796:T:C	L1686S	0.995

dbSNP variants (sampled 300 via entrez): RS1000016419 (4:76598545 C>G), RS1000016770 (4:76523985 A>C), RS10000169 (4:76435093 C>T), RS1000020579 (4:76662827 G>A), RS1000021788 (4:76591842 C>A), RS1000023182 (4:76530317 T>G), RS1000034521 (4:76670251 T>C), RS1000045294 (4:76720427 T>C,G), RS1000060725 (4:76479156 A>C), RS1000068461 (4:76474235 A>C), RS1000083469 (4:76571094 A>T), RS1000103692 (4:76458253 T>G), RS1000111558 (4:76471296 T>G), RS1000121927 (4:76731565 G>A), RS1000132533 (4:76696855 G>A)

Disease associations

OMIM: gene MIM:604570 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neural tube defect	Strong	Autosomal dominant
syndromic disease	Moderate	Autosomal recessive

Mondo (2): syndromic disease (MONDO:0002254), neural tube defect (MONDO:0018075)

Orphanet (0):

HPO phenotypes

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

GWAS associations

65 associations (top):

Study	Trait	p-value
GCST000397_4	Renal function and chronic kidney disease	1.000000e-12
GCST000649_16	Chronic kidney disease	1.000000e-19
GCST000651_2	Creatinine levels	6.000000e-09
GCST000756_7	Magnesium levels	6.000000e-13
GCST001606_5	Renal function-related traits (sCR)	9.000000e-12
GCST001607_3	Renal function-related traits (eGRFcrea)	7.000000e-11
GCST001923_3	Glomerular filtration rate	2.000000e-09
GCST001923_6	Glomerular filtration rate	1.000000e-08
GCST002933_2	Magnesium levels	6.000000e-06
GCST003372_14	Glomerular filtration rate (creatinine)	1.000000e-37
GCST003374_4	Chronic kidney disease	8.000000e-06
GCST003401_31	Glomerular filtration rate in non diabetics (creatinine)	5.000000e-35
GCST003790_10	Glomerular filtration rate	1.000000e-15
GCST003790_35	Glomerular filtration rate	4.000000e-06
GCST003790_36	Glomerular filtration rate	6.000000e-12
GCST003875_46	Gut microbiota (bacterial taxa)	2.000000e-10
GCST003875_47	Gut microbiota (bacterial taxa)	2.000000e-10
GCST004292_14	Glomerular filtration rate (creatinine)	3.000000e-37
GCST004412_8	Craniofacial microsomia	8.000000e-08
GCST004601_56	Red blood cell count	1.000000e-13
GCST004604_93	Hematocrit	1.000000e-13
GCST004615_17	Hemoglobin concentration	2.000000e-12
GCST005194_117	Coronary artery disease	4.000000e-10
GCST005195_90	Coronary artery disease	2.000000e-10
GCST005196_117	Coronary artery disease	4.000000e-10
GCST005984_28	Glomerular filtration rate	5.000000e-28
GCST005985_45	Creatinine levels	2.000000e-29
GCST005998_11	Alanine transaminase levels	3.000000e-12
GCST006101_1	Cardiometabolic and hematological traits	1.000000e-14
GCST006586_12	Urinary albumin excretion	1.000000e-09

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004845	magnesium measurement
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004285	albuminuria
EFO:0007796	parental longevity
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004530	triglyceride measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009436	Neural Tube Defects	C10.500.680; C16.131.666.680
D013577	Syndrome	C23.550.288.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067279 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.34	Kd	457.2	nM	CHEMBL5653589
6.34	ED50	457.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149394: Binding affinity to human SHROOM3 incubated for 45 mins by Kinobead based pull down assay	kd	0.4572	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	decreases expression, affects cotreatment	4
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
Valproic Acid	affects expression, decreases expression, increases expression	3
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression, decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
bisphenol A	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
coumarin	affects phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Aerosols	increases expression	1
Air Pollutants	affects methylation, increases abundance	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Coumestrol	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652436	Binding	Binding affinity to human SHROOM3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
NCT02230072	PHASE1	COMPLETED	Fetoscopic Meningomyelocele Repair Study
NCT00213447	Not specified	COMPLETED	T Cell Response in Hypersensitivity Syndrome
NCT02240888	Not specified	COMPLETED	Vaccination in Inflammatory Rheumatic Disease (VACCIMIL). The Impact of Antirheumatic Treatment on Antibody Response
NCT02526082	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up of the Helsinki Businessmen Study
NCT02637518	Not specified	UNKNOWN	Comprehensive Validation of Frailty Assessment Tools in Older Adults in Different Clinical and Social Settings
NCT02971072	Not specified	COMPLETED	Neurophysiology of Weakness and Exercise in Rotator Cuff Tendinopathy
NCT02974569	Not specified	COMPLETED	Improving Symptom Self-management in Adolescents & Young Adults With Cancer
NCT03265561	Not specified	COMPLETED	Spinal Infection Management With Structural Allograft
NCT04190342	Not specified	COMPLETED	Effects of a Traditional Chinese Exercise Program on Symptom Cluster in Breast Cancer Patients
NCT04874584	Not specified	COMPLETED	Culturally Tailored Nurse Coaching Study for Cancer Symptom Management
NCT04909489	Not specified	UNKNOWN	PDR and SKYD of Dyslipidemia’s Characteristics From the Oxidative Stress Enhancement Caused by Inhibition of Serine Metabolic Pathway
NCT05218122	Not specified	UNKNOWN	Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited
NCT05266118	Not specified	COMPLETED	Patient Reported Symptoms the First Week After Intensive Care Unit Discharge and up to Hospital Discharge
NCT05321966	Not specified	COMPLETED	The Effect of Video Training on Symptom Burden Patients Undergoing Hemodialysis Treatment
NCT05818748	Not specified	UNKNOWN	Effect Of Virtual Reality Distraction on Symptom Control and Anxiety in Children With Leukemia
NCT05837988	Not specified	UNKNOWN	Construction of Symptom Network in Maintenance Hemodialysis Patients
NCT06143436	Not specified	UNKNOWN	TCM Constitution, Pattern Types, and Disease Factors in Primary Lung Cancer.
NCT06222008	Not specified	UNKNOWN	Study on Symptom Clusters During Chemotherapy in Ovarian Cancer Patients With Different Chinese Medicine Constitution
NCT06412107	Not specified	COMPLETED	Somatic Acupressure for Symptom Cluster Management in Breast Cancer Survivors
NCT06847360	Not specified	RECRUITING	Home-based Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for IBS Pain
NCT07281300	Not specified	RECRUITING	Mindfulness-Oriented Respiratory Distress Symptom Intervention for Lung Cancer
NCT07315672	Not specified	RECRUITING	Acupressure for Cough in Lung Cancer Survivors
NCT07479654	Not specified	NOT_YET_RECRUITING	AI-Enabled Frailty Risk Prediction in Adult Congenital Heart Disease
NCT07495358	Not specified	NOT_YET_RECRUITING	Development and Usability Evaluation of a Knowledge Graph-Based Symptom Management System for Patients With Breast Cancer Undergoing Chemotherapy
NCT07576114	Not specified	RECRUITING	Comparison of Gluteal Muscle Activation and Core Strengthening in Dead Butt Syndrome Syndrome
NCT00060606	Not specified	COMPLETED	Management of Myelomeningocele Study (MOMS)
NCT00966927	Not specified	ACTIVE_NOT_RECRUITING	Assessment of Functional Independence and Quality of Life in Adolescents With Spina Bifid
NCT00975338	Not specified	COMPLETED	The LETS Study: A Longitudinal Evaluation of Transition Services
NCT02592291	Not specified	RECRUITING	Mobile Health Self-Management and Support System for Chronic and Complex Health Conditions
NCT03044821	Not specified	TERMINATED	Open Myelomeningocele Repair With High Maternal BMI
NCT03090633	Not specified	ACTIVE_NOT_RECRUITING	Fetoscopic Repair of Isolated Fetal Spina Bifida
NCT03544970	Not specified	COMPLETED	An Audit of the Posterior Fossa Characterization in Open Spina Bifida Based on Tertiary Center Experience
NCT04763382	Not specified	UNKNOWN	The Effect of Nursing Interventions for Clean Intermittent Catheterization Caregivers and Child
NCT05718440	Not specified	RECRUITING	Uronephrological Complications Risk Factors in Spinal Dysraphism
NCT05962086	Not specified	UNKNOWN	Determining Developmental and Clinical Markers Affecting Urinary Function of Children With Spinal Dysraphism
NCT06907732	Not specified	NOT_YET_RECRUITING	Fetoscopic Robotic Open Spina Bifida Treatment