DAAM2

Summary

DAAM2 (dishevelled associated activator of morphogenesis 2, HGNC:18143) is a protein-coding gene on chromosome 6p21.2, encoding Disheveled-associated activator of morphogenesis 2 (Q86T65). Key regulator of the Wnt signaling pathway, which is required for various processes during development, such as dorsal patterning, determination of left/right symmetry or myelination in the central nervous system.

Predicted to enable actin binding activity and small GTPase binding activity. Involved in several processes, including podocyte cell migration; regulation of actin filament polymerization; and regulation of filopodium assembly. Located in extracellular exosome. Implicated in familial nephrotic syndrome.

Source: NCBI Gene 23500 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome, type 24 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 283 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 23
• MANE Select transcript: NM_001201427

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18143
Approved symbol	DAAM2
Name	dishevelled associated activator of morphogenesis 2
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0381, NPHS24
Ensembl gene	ENSG00000146122
Ensembl biotype	protein_coding
OMIM	606627
Entrez	23500

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 19 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000274867, ENST00000398904, ENST00000405961, ENST00000475489, ENST00000491083, ENST00000494405, ENST00000496787, ENST00000538976, ENST00000631498, ENST00000632657, ENST00000633794, ENST00000853736, ENST00000853737, ENST00000853738, ENST00000853739, ENST00000853740, ENST00000853741, ENST00000853742, ENST00000853743, ENST00000853744, ENST00000853745, ENST00000924855, ENST00000961718, ENST00000961719, ENST00000961720

RefSeq mRNA: 2 — MANE Select: NM_001201427 NM_001201427, NM_015345

CCDS: CCDS54999, CCDS56426

Canonical transcript exons

ENST00000274867 — 25 exons

Exon	Start	End
ENSE00000974082	39868823	39868933
ENSE00000974083	39870340	39870443
ENSE00000974084	39871506	39871572
ENSE00000974085	39873238	39873355
ENSE00000974088	39878404	39878588
ENSE00000974089	39879178	39879477
ENSE00000974090	39883962	39884069
ENSE00000974091	39887486	39887592
ENSE00000974093	39891341	39891447
ENSE00000974094	39891634	39891722
ENSE00000974095	39896812	39896980
ENSE00000974096	39897175	39897282
ENSE00000974097	39898877	39898937
ENSE00000974098	39900077	39900208
ENSE00000974099	39901302	39901472
ENSE00001216576	39867510	39867843
ENSE00001382192	39901813	39904869
ENSE00003458225	39875330	39875468
ENSE00003494490	39860928	39861017
ENSE00003531670	39864433	39864507
ENSE00003533201	39864980	39865074
ENSE00003549792	39856247	39856470
ENSE00003628231	39888679	39888763
ENSE00003668809	39878203	39878261
ENSE00003783797	39792376	39792465

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 98.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3949 / max 761.1109, expressed in 965 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67688	15.8265	961
67689	0.1823	67
67693	0.1690	65
67709	0.0735	33
67690	0.0627	37
67691	0.0440	26
67692	0.0369	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	98.85	gold quality
middle frontal gyrus	UBERON:0002702	98.73	gold quality
inferior vagus X ganglion	UBERON:0005363	98.67	gold quality
lateral globus pallidus	UBERON:0002476	98.32	gold quality
subthalamic nucleus	UBERON:0001906	98.28	gold quality
spinal cord	UBERON:0002240	98.22	gold quality
globus pallidus	UBERON:0001875	98.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.17	gold quality
medial globus pallidus	UBERON:0002477	98.12	gold quality
inferior olivary complex	UBERON:0002127	98.10	gold quality
medulla oblongata	UBERON:0001896	97.97	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.95	gold quality
ventral tegmental area	UBERON:0002691	97.87	gold quality
substantia nigra	UBERON:0002038	97.67	gold quality
midbrain	UBERON:0001891	97.66	gold quality
CA1 field of hippocampus	UBERON:0003881	97.34	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.31	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.26	gold quality
lower esophagus	UBERON:0013473	97.19	gold quality
superior vestibular nucleus	UBERON:0007227	97.17	gold quality
cranial nerve II	UBERON:0000941	97.11	gold quality
amygdala	UBERON:0001876	96.79	gold quality
putamen	UBERON:0001874	96.69	gold quality
substantia nigra pars compacta	UBERON:0001965	96.67	gold quality
Ammon’s horn	UBERON:0001954	96.49	gold quality
hypothalamus	UBERON:0001898	96.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.23	gold quality
mucosa of stomach	UBERON:0001199	95.69	gold quality
caudate nucleus	UBERON:0001873	95.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	592.31
E-HCAD-35	yes	73.33
E-ANND-3	yes	10.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

164 targeting DAAM2, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718

Literature-anchored findings (GeneRIF, showing 8)

• miR-335 regulates the expression of at least five formin family members, three of which are validated, FMNL3, FMN2 and DAAM2. (PMID:24223803)
• Reduction of Daam2 expression occurred with clinical improvement of the patients (PMID:26293489)
• Biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. (PMID:29053101)
• DAAM2 Variants Cause Nephrotic Syndrome via Actin Dysregulation. (PMID:33232676)
• DAAM2 is elevated in the circulation and placenta in pregnancies complicated by fetal growth restriction and is regulated by hypoxia. (PMID:33692394)
• Disheveled-associated activator of morphogenesis 2 promotes invasion of colorectal cancer by activating PAK1 and promoting MMP7 expression. (PMID:33974241)
• Placental DAAM2 is unaltered in preeclampsia, but upregulated by treatment with proton pump inhibitors. (PMID:35933758)
• The prognostic value of DAAM2 in lower grade glioma, liver cancer, and breast cancer. (PMID:36790676)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	daam2	ENSDARG00000028393
mus_musculus	Daam2	ENSMUSG00000040260
rattus_norvegicus	Daam2	ENSRNOG00000053945
caenorhabditis_elegans		WBGENE00018976

Paralogs (18): DAAM1 (ENSG00000100592), FNBP4 (ENSG00000109920), DIAPH1 (ENSG00000131504), FHOD3 (ENSG00000134775), FHOD1 (ENSG00000135723), FHDC1 (ENSG00000137460), DIAPH3 (ENSG00000139734), DIAPH2 (ENSG00000147202), FMN2 (ENSG00000155816), FMNL2 (ENSG00000157827), FMNL3 (ENSG00000161791), FMNL1 (ENSG00000184922), FAM47A (ENSG00000185448), SHTN1 (ENSG00000187164), FAM47B (ENSG00000189132), FAM47C (ENSG00000198173), INF2 (ENSG00000203485), GRID2IP (ENSG00000215045)

Protein

Protein identifiers

Disheveled-associated activator of morphogenesis 2 — Q86T65 (reviewed: Q86T65)

All UniProt accessions (4): Q86T65, A0A0J9YX09, A0A0J9YYF7, F2Z2Q2

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of the Wnt signaling pathway, which is required for various processes during development, such as dorsal patterning, determination of left/right symmetry or myelination in the central nervous system. Acts downstream of Wnt ligands and upstream of beta-catenin (CTNNB1). Required for canonical Wnt signaling pathway during patterning in the dorsal spinal cord by promoting the aggregation of Disheveled (Dvl) complexes, thereby clustering and formation of Wnt receptor signalosomes and potentiating Wnt activity. During dorsal patterning of the spinal cord, inhibits oligodendrocytes differentiation via interaction with PIP5K1A. Also regulates non-canonical Wnt signaling pathway. Acts downstream of PITX2 in the developing gut and is required for left/right asymmetry within dorsal mesentery: affects mesenchymal condensation by lengthening cadherin-based junctions through WNT5A and non-canonical Wnt signaling, inducing polarized condensation in the left dorsal mesentery necessary to initiate gut rotation. Together with DAAM1, required for myocardial maturation and sarcomere assembly. Is a regulator of actin nucleation and elongation, filopodia formation and podocyte migration.

Subunit / interactions. Interacts with DVL3. Interacts with INF2.

Tissue specificity. Expressed in most tissues examined. Expressed in kidney glomeruli.

Disease relevance. Nephrotic syndrome 24 (NPHS24) [MIM:619263] A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS24 is an autosomal recessive, slowly progressive form. Most patients eventually develop end-stage renal disease. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The DAD domain regulates activation via an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments.

Similarity. Belongs to the formin homology family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86T65-3	1	yes
Q86T65-4	2

RefSeq proteins (2): NP_001188356, NP_056160 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010472	FH3_dom	Domain
IPR010473	GTPase-bd	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR014767	DAD_dom	Domain
IPR014768	GBD/FH3_dom	Domain
IPR015425	FH2_Formin	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR042201	FH2_Formin_sf	Homologous_superfamily
IPR051425	Formin_Homology	Family

Pfam: PF02181, PF06367, PF06371

UniProt features (20 total): sequence variant 7, domain 4, sequence conflict 3, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86T65-F1	80.02	0.43

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): 1015

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 233 (showing top): ATF_B, GOBP_SPINAL_CORD_DEVELOPMENT, RRAGTTGT_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, PAX4_01, GOBP_NEGATIVE_REGULATION_OF_OLIGODENDROCYTE_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, CREBP1_Q2, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (14): determination of left/right symmetry (GO:0007368), Wnt signaling pathway (GO:0016055), dorsal spinal cord development (GO:0021516), actin cytoskeleton organization (GO:0030036), positive regulation of cell migration (GO:0030335), regulation of actin filament polymerization (GO:0030833), regulation of actin cytoskeleton organization (GO:0032956), negative regulation of oligodendrocyte differentiation (GO:0048715), regulation of filopodium assembly (GO:0051489), regulation of canonical Wnt signaling pathway (GO:0060828), positive regulation of canonical Wnt signaling pathway (GO:0090263), podocyte cell migration (GO:0090521), regulation of non-canonical Wnt signaling pathway (GO:2000050), cellular component organization (GO:0016043)

GO Molecular Function (3): actin binding (GO:0003779), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (1): extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of Wnt signaling pathway	2
canonical Wnt signaling pathway	2
determination of bilateral symmetry	1
left/right pattern formation	1
cell surface receptor signaling pathway	1
spinal cord development	1
anatomical structure development	1
cytoskeleton organization	1
actin filament-based process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
negative regulation of glial cell differentiation	1
oligodendrocyte differentiation	1
regulation of oligodendrocyte differentiation	1
filopodium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
positive regulation of Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
epithelial cell migration	1
non-canonical Wnt signaling pathway	1
cellular component organization or biogenesis	1
cytoskeletal protein binding	1
GTPase binding	1
binding	1
extracellular vesicle	1

Protein interactions and networks

STRING

2012 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAAM2	DVL1	O14640	901
DAAM2	VANGL1	Q8TAA9	619
DAAM2	FNBP4	Q8N3X1	594
DAAM2	WBP4	O75554	585
DAAM2	FNBP1	Q96RU3	565
DAAM2	PRPF40A	O75400	541
DAAM2	AXIN1	O15169	510
DAAM2	PFN4	Q8NHR9	509
DAAM2	SRGAP2	O75044	502
DAAM2	RYK	P34925	502
DAAM2	PTK7	Q13308	502
DAAM2	PIKFYVE	Q9Y2I7	501
DAAM2	CDH2	P19022	472
DAAM2	FMN1	Q68DA7	450
DAAM2	PRICKLE1	Q96MT3	449

IntAct

22 interactions, top by confidence:

A	B	Type	Score
RHOA	CTSA	psi-mi:“MI:0914”(association)	0.730
RHOC	RAP1GDS1	psi-mi:“MI:0914”(association)	0.730
RHOD	PLXNB2	psi-mi:“MI:0914”(association)	0.640
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
RHOC	ARHGEF11	psi-mi:“MI:0914”(association)	0.530
DAAM2	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
C1orf198	INPPL1	psi-mi:“MI:0914”(association)	0.530
rep	DAAM2	psi-mi:“MI:0915”(physical association)	0.490
SPG11	DAAM2	psi-mi:“MI:0915”(physical association)	0.370
ORF43	ANXA7	psi-mi:“MI:0914”(association)	0.350
DYNLT4	NPR1	psi-mi:“MI:0914”(association)	0.350
FYN	MYCBP2	psi-mi:“MI:0914”(association)	0.350
OSTM1	ASMTL	psi-mi:“MI:0914”(association)	0.350
SLC1A3	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLC1A6	ILVBL	psi-mi:“MI:0914”(association)	0.350
MDM2	DAAM2	psi-mi:“MI:0915”(physical association)	0.000
TIAM1	DAAM2	psi-mi:“MI:0915”(physical association)	0.000
TTC3	DAAM2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): DAAM2 (Two-hybrid), DAAM2 (Two-hybrid), DAAM2 (Two-hybrid), KRT40 (Two-hybrid), RBMY1F (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), DAAM2 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), CD320 (Affinity Capture-MS), PRAME (Affinity Capture-MS), LGR4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5P556, A6H7I5, B0DOB5, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EGS5, H2KZZ6, O95466, P21575, P23678, P27619, P39052, P39053, P39054, P39055, P48608, P50570, P78344, P79398, Q01968, Q05193, Q08877, Q08DF4, Q15057, Q15172, Q24564, Q2KI89, Q5R629, Q5R7J9, Q5ZK62, Q62448, Q6IVG4, Q6NXC0, Q6ZQK5, Q7SIG6, Q7XPJ0, Q80U19, Q86T65

Diamond homologs: A0A1D5P556, A4D2P6, B0DOB5, O08808, O23373, O60610, O70566, Q6MWG9, Q80U19, Q86T65, Q8BPM0, Q9FJX6, Q9Y4D1, A0A8C0TYJ0, A5PKA5, A8MUH7, B7WN72, G5ECY0, O08774, O14745, O14924, O15085, O60879, P31007, P31016, P70175, P70441, P78352, P97879, Q09506, Q0D5P3, Q0QWG9, Q12959, Q13425, Q15599, Q15700, Q28619, Q28C55, Q3T0X8, Q3UHD6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	192
Likely benign	41
Benign	23

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1054666	NM_001201427.2(DAAM2):c.361G>C (p.Glu121Gln)	Pathogenic
1054669	NM_001201427.2(DAAM2):c.1004G>A (p.Arg335Gln)	Pathogenic
1054670	NM_001201427.2(DAAM2):c.1333C>T (p.Arg445Ter)	Pathogenic
3391004	NM_001201427.2(DAAM2):c.196C>T (p.Arg66Ter)	Likely pathogenic
4278020	NM_001201427.2(DAAM2):c.3058G>T (p.Gly1020Ter)	Likely pathogenic

SpliceAI

4601 predictions. Top by Δscore:

Variant	Effect	Δscore
6:39856245:A:AG	acceptor_gain	1.0000
6:39856246:G:GG	acceptor_gain	1.0000
6:39856468:GTG:G	donor_gain	1.0000
6:39856475:G:GG	donor_gain	1.0000
6:39860922:TTGCA:T	acceptor_loss	1.0000
6:39860923:TGCA:T	acceptor_loss	1.0000
6:39860924:GCAGG:G	acceptor_loss	1.0000
6:39860925:CA:C	acceptor_loss	1.0000
6:39860926:A:AG	acceptor_gain	1.0000
6:39860926:A:C	acceptor_loss	1.0000
6:39860926:AG:A	acceptor_gain	1.0000
6:39860927:G:GG	acceptor_gain	1.0000
6:39860927:GG:G	acceptor_gain	1.0000
6:39860927:GGAT:G	acceptor_gain	1.0000
6:39861011:G:GT	donor_gain	1.0000
6:39861014:G:GT	donor_gain	1.0000
6:39861015:A:T	donor_gain	1.0000
6:39864429:TCA:T	acceptor_loss	1.0000
6:39864431:A:AT	acceptor_loss	1.0000
6:39864432:G:C	acceptor_loss	1.0000
6:39864432:GGA:G	acceptor_gain	1.0000
6:39864505:GCG:G	donor_gain	1.0000
6:39864508:G:GG	donor_gain	1.0000
6:39864508:GTGA:G	donor_loss	1.0000
6:39864509:T:G	donor_loss	1.0000
6:39864970:T:A	acceptor_gain	1.0000
6:39865072:GAGG:G	donor_loss	1.0000
6:39865073:AGGTA:A	donor_loss	1.0000
6:39865074:GGTAA:G	donor_loss	1.0000
6:39865075:GTA:G	donor_loss	1.0000

AlphaMissense

7095 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:39860941:T:C	L61P	1.000
6:39860956:G:C	R66P	1.000
6:39860991:T:A	W78R	1.000
6:39860991:T:C	W78R	1.000
6:39864470:C:A	P99H	1.000
6:39865044:T:C	L133P	1.000
6:39865052:G:C	A136P	1.000
6:39865056:T:A	L137H	1.000
6:39865056:T:C	L137P	1.000
6:39865059:G:C	R138P	1.000
6:39867511:T:C	F144L	1.000
6:39867512:T:C	F144S	1.000
6:39867512:T:G	F144C	1.000
6:39867513:T:A	F144L	1.000
6:39867513:T:G	F144L	1.000
6:39867523:T:C	F148L	1.000
6:39867524:T:C	F148S	1.000
6:39867525:C:A	F148L	1.000
6:39867525:C:G	F148L	1.000
6:39867538:G:C	G153R	1.000
6:39867539:G:A	G153D	1.000
6:39867621:C:G	C180W	1.000
6:39867627:A:C	K182N	1.000
6:39867627:A:T	K182N	1.000
6:39867639:C:A	N186K	1.000
6:39867639:C:G	N186K	1.000
6:39867649:G:A	G190R	1.000
6:39867649:G:C	G190R	1.000
6:39867649:G:T	G190W	1.000
6:39867650:G:A	G190E	1.000

dbSNP variants (sampled 300 via entrez): RS1000024659 (6:39899973 A>G), RS1000033905 (6:39831699 GGGGTA>G), RS1000068916 (6:39818463 T>C), RS1000076200 (6:39799856 A>C), RS1000148083 (6:39838948 C>A,G,T), RS1000175098 (6:39844319 A>G), RS1000181278 (6:39879210 G>A), RS1000263029 (6:39852010 G>C), RS1000276674 (6:39834622 TA>T), RS1000283582 (6:39846068 A>G), RS1000284060 (6:39794163 A>C), RS1000288266 (6:39834380 G>C), RS1000334052 (6:39845801 C>G), RS1000340210 (6:39874324 G>A), RS1000340661 (6:39892215 A>T)

Disease associations

OMIM: gene MIM:606627 | disease phenotypes: MIM:619263, MIM:252150

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome, type 24	Strong	Autosomal recessive
androgen insensitivity syndrome	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
idiopathic multidrug-resistant nephrotic syndrome	Limited	AR

Mondo (4): nephrotic syndrome, type 24 (MONDO:0031008), idiopathic multidrug-resistant nephrotic syndrome (MONDO:0035459), sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (MONDO:0009643), androgen insensitivity syndrome (MONDO:0019154)

Orphanet (4): Idiopathic steroid-resistant nephrotic syndrome (Orphanet:567548), Idiopathic multidrug-resistant nephrotic syndrome (Orphanet:567550), Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (Orphanet:308386), Encephalopathy due to sulfite oxidase deficiency (Orphanet:833)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000969	Edema
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0003073	Hypoalbuminemia
HP:0003621	Juvenile onset
HP:0003774	Stage 5 chronic kidney disease
HP:0011463	Childhood onset
HP:0011947	Respiratory tract infection
HP:0012579	Minimal change glomerulonephritis
HP:0012588	Steroid-resistant nephrotic syndrome
HP:0012622	Chronic kidney disease
HP:0031266	Podocyte foot process effacement
HP:0031504	Foamy urine
HP:0033132	Renal cortical hyperechogenicity
HP:0100539	Periorbital edema

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000544_7	Pulmonary function	8.000000e-08
GCST002563_8	Hypospadias	7.000000e-25
GCST006412_56	Intraocular pressure	4.000000e-08
GCST006979_277	Heel bone mineral density	4.000000e-10
GCST008839_206	Height	4.000000e-10
GCST010702_24	Subcortical volume (MOSTest)	2.000000e-42
GCST010703_83	Brain morphology (MOSTest)	7.000000e-16
GCST90000025_498	Appendicular lean mass	2.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013734	Androgen-Insensitivity Syndrome	C12.050.351.875.253.096.500; C12.200.706.316.096.500; C12.800.316.096.500; C16.131.939.316.096.500; C16.320.322.061; C19.391.119.096.500
C565372	Molybdenum Cofactor Deficiency, Complementation Group A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Dexamethasone	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Particulate Matter	decreases abundance, increases expression, decreases expression, increases abundance, affects cotreatment	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Allergens	increases expression, affects cotreatment, decreases abundance	1
Arsenic	increases methylation	1
Vehicle Emissions	decreases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Endosulfan	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Paraquat	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9CX	Ubigene HEK293 DAAM2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04422366	PHASE3	RECRUITING	Evaluate the Efficacy, Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females
NCT04425291	PHASE3	COMPLETED	Evaluate the Immunogenicity and Safety of 4-valent and 9-valent HPV Recombinant Vaccine in Chinese Healthy Females
NCT04895020	PHASE3	RECRUITING	Immunobridging Study of 9-valent Human Papillomavirus Recombinant Vaccine in Chinese Females Aged 9 to 19 Years
NCT05372016	PHASE3	COMPLETED	Evaluate the Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females
NCT05584332	PHASE3	TERMINATED	A Phase Ⅲ Study to Evaluate the Efficacy, Immunogenicity, Safety of Quadrivalent HPV Recombinant Vaccine in Chinese Healthy Females
NCT07520565	PHASE3	RECRUITING	A Multicentre, Randomised, Double-blind, Placebo-parallel Controlled Phase Ⅲ Clinical Trial Evaluating the Efficacy and Safety of BXOS110 Injection in the Treatment of Acute Ischaemic Stroke Within 3 Hours of Onset.
NCT02905565	PHASE2	COMPLETED	NBP in Adult Patients With Acute Ischemic Stroke (AIS)
NCT03676101	PHASE1	COMPLETED	Evaluate the Safety and Primary Immunogenicity of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females
NCT03105063	Not specified	UNKNOWN	Evaluation of the AIIS Using Hip Ultrasound(AIISUS)
NCT04252001	Not specified	NOT_YET_RECRUITING	Growing up With the Young Endocrine Support System (YESS!)
NCT04708431	Not specified	RECRUITING	Androgen Receptor, Implications for Health and Wellbeing: Natural History Study of Individuals With Androgen Insensitivity
NCT05152329	Not specified	UNKNOWN	Investigating the Potential Psychological Impact of Early Screening and Long-term Monitoring for Adolescent Idiopathic Scoliosis Among Patients and Caregivers
NCT05466383	Not specified	RECRUITING	Screening and Intervention for AIS in Haikou, Hainan Province, China
NCT05473975	Not specified	COMPLETED	Search for a Recanalization of the Sylvian Artery Electro-Physiological Biomarker
NCT05496361	Not specified	COMPLETED	A Prospective, Multi-center and Randomized Controlled Trial of Tianyi Revascularization Device in Acute Ischemic Stroke
NCT06251505	Not specified	COMPLETED	Cervical Alignment Changes After Correction of Thoracic Adolescent Idiopathic Scoliosis With Thoracic Hypokyphosis
NCT06702657	Not specified	NOT_YET_RECRUITING	A Randomized Clinical Trial on Urgent Angioplasty for IntraCranial Atherosclerotic Stenosis-related Large-Vessel Occlusion After Mechanical Thrombectomy
NCT07194564	Not specified	ACTIVE_NOT_RECRUITING	Acute Training Effect Assessment in Adolescent Idiopathic Scoliosis