NCKIPSD

Summary

NCKIPSD (NCK interacting protein with SH3 domain, HGNC:15486) is a protein-coding gene on chromosome 3p21.31, encoding NCK-interacting protein with SH3 domain (Q9NZQ3). Has an important role in stress fiber formation induced by active diaphanous protein homolog 1 (DRF1).

The protein encoded by this gene contains a nuclear localization signal. It plays a role in signal transduction, and may function in the maintenance of sarcomeres and in the assembly of myofibrils into sarcomeres. It also plays an important role in stress fiber formation This protein is involved in the formation and maintenance of dendritic spines, and modulates synaptic activity in neurons. The gene is involved in therapy-related leukemia by a chromosomal translocation t(3;11)(p21;q23) that involves this gene and the myeloid/lymphoid leukemia gene. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 51517 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 131 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_016453

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15486
Approved symbol	NCKIPSD
Name	NCK interacting protein with SH3 domain
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	AF3P21, SPIN90, ORF1, WISH, WASLBP, DIP1
Ensembl gene	ENSG00000213672
Ensembl biotype	protein_coding
OMIM	606671
Entrez	51517

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000294129, ENST00000413374, ENST00000415281, ENST00000416649, ENST00000426678, ENST00000439518, ENST00000453349, ENST00000454134, ENST00000470006, ENST00000870676, ENST00000870677, ENST00000870678, ENST00000870679, ENST00000870680, ENST00000870681, ENST00000870682, ENST00000870683, ENST00000870684, ENST00000870685, ENST00000967715, ENST00000967716, ENST00000967717, ENST00000967718, ENST00000967719, ENST00000967720

RefSeq mRNA: 2 — MANE Select: NM_016453 NM_016453, NM_184231

CCDS: CCDS2776, CCDS46827

Canonical transcript exons

ENST00000294129 — 13 exons

Exon	Start	End
ENSE00001063255	48679801	48679887
ENSE00001063261	48682903	48683012
ENSE00001063262	48679575	48679713
ENSE00001063264	48678877	48678969
ENSE00001063269	48679055	48679183
ENSE00001204828	48680059	48680229
ENSE00001204831	48681287	48681780
ENSE00001304328	48673844	48674747
ENSE00003468494	48682348	48682552
ENSE00003487335	48678564	48678736
ENSE00003553076	48679377	48679457
ENSE00003665117	48682045	48682156
ENSE00003848757	48685637	48685915

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 95.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1938 / max 114.1625, expressed in 1774 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42165	12.8047	1769
42164	0.3891	155

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	95.01	gold quality
prefrontal cortex	UBERON:0000451	94.95	gold quality
middle temporal gyrus	UBERON:0002771	94.90	gold quality
primary visual cortex	UBERON:0002436	94.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.13	gold quality
frontal cortex	UBERON:0001870	94.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.68	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.63	gold quality
right atrium auricular region	UBERON:0006631	93.51	gold quality
neocortex	UBERON:0001950	93.48	gold quality
cerebellar hemisphere	UBERON:0002245	93.47	gold quality
cerebellar cortex	UBERON:0002129	93.41	gold quality
anterior cingulate cortex	UBERON:0009835	93.15	gold quality
cingulate cortex	UBERON:0003027	93.12	gold quality
cardiac atrium	UBERON:0002081	92.94	gold quality
occipital lobe	UBERON:0002021	92.84	gold quality
superior frontal gyrus	UBERON:0002661	92.72	gold quality
left ovary	UBERON:0002119	92.65	gold quality
cerebellum	UBERON:0002037	92.52	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.49	gold quality
postcentral gyrus	UBERON:0002581	92.45	gold quality
right ovary	UBERON:0002118	92.35	gold quality
descending thoracic aorta	UBERON:0002345	92.23	gold quality
ascending aorta	UBERON:0001496	92.04	gold quality
cerebral cortex	UBERON:0000956	92.01	gold quality
apex of heart	UBERON:0002098	92.00	gold quality
thoracic aorta	UBERON:0001515	91.99	gold quality
parietal lobe	UBERON:0001872	91.97	gold quality
left coronary artery	UBERON:0001626	91.77	gold quality
CA1 field of hippocampus	UBERON:0003881	91.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting NCKIPSD, 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-4455	100.00	65.48	1587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4728-3P	99.47	68.94	981

Literature-anchored findings (GeneRIF, showing 13)

• the interaction of the betaPIX.WASP.SPIN90 complex with Nck is crucial for stable cell adhesion and can be dynamically modulated by SPIN90 phosphorylation that is dependent on cell adhesion and ERK activation (PMID:14559906)
• SPIN90 participates in reorganization of the actin cytoskeleton and in actin-based cell motility (PMID:16253999)
• DIP binds to and inhibits actin assembly by the FH2 domain of the formin mDia2 (PMID:17398099)
• These observations point to a pivotal role for DIP in the control of nonbranched and branched actin-filament assembly that is mediated by Diaphanous-related formins and activators of Arp2/3, respectively. (PMID:17398099)
• The interplay between palladin, SPIN90 and Src and characterized the role of palladin and SPIN90 in platelet derived growth factor and Src-induced cytoskeletal remodeling, was analyzed. (PMID:17537434)
• SPIN90 and IRSp53 positively cooperated to mediate Rac activation, and co-expression of SPIN90 and IRSp53 in COS-7 cells led to the complex formation of SPIN90-IRSp53 in the leading edge of cells (PMID:19460367)
• Dia2 and DIP co-tether to nascent blebs and this linkage is required for bleb formation. (PMID:23024796)
• Findings show that SPIN90 modulates synaptic activity in neurons as a result of its phosphorylation. (PMID:23342115)
• SPIN90 dephosphorylation is a prerequisite step for releasing cofilin so that cofilin can adequately sever actin filaments into monomeric form. (PMID:23765104)
• findings suggest that SPIN90 contributes to the formation and movement of endosomal vesicles, and modulates the stability of EGFR protein, which affects cell cycle progression (PMID:24340049)
• Low SPIN90 expression is associated with Breast Cancer. (PMID:28652253)
• Structure of the nucleation-promoting factor SPIN90 bound to the actin filament nucleator Arp2/3 complex. (PMID:30322896)
• The findings suggest that SPIN90, as an adaptor protein, simultaneously binds inactive Rab5 and Gapex5, thereby altering their spatial proximity and facilitating Rab5 activation. (PMID:31358736)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nckipsd	ENSDARG00000079475
mus_musculus	Nckipsd	ENSMUSG00000032598
rattus_norvegicus	Nckipsd	ENSRNOG00000031816
drosophila_melanogaster	CG2258	FBGN0029997

Protein

Protein identifiers

NCK-interacting protein with SH3 domain — Q9NZQ3 (reviewed: Q9NZQ3)

Alternative names: 54 kDa VacA-interacting protein, 54 kDa vimentin-interacting protein, 90 kDa SH3 protein interacting with Nck, AF3p21, Dia-interacting protein 1, Diaphanous protein-interacting protein, SH3 adapter protein SPIN90, WASP-interacting SH3-domain protein, Wiskott-Aldrich syndrome protein-interacting protein

All UniProt accessions (7): C9JC20, C9JMQ4, C9JSC3, Q9NZQ3, F8WCR8, H7C0T9, H7C2K2

UniProt curated annotations — full annotation on UniProt →

Function. Has an important role in stress fiber formation induced by active diaphanous protein homolog 1 (DRF1). Induces microspike formation, in vivo. In vitro, stimulates N-WASP-induced ARP2/3 complex activation in the absence of CDC42. May play an important role in the maintenance of sarcomeres and/or in the assembly of myofibrils into sarcomeres. Implicated in regulation of actin polymerization and cell adhesion. Plays a role in angiogenesis.

Subunit / interactions. Associates with the intermediate filaments, vimentin and desmin. Binds the first and third SH3 domains of NCK. Binds the proline-rich domains of N-WASP through its SH3 domain. Similarly, binds diaphanous protein homolog 1 (DRF1). Binds the SH3 domains of GRB2 through its proline-rich domains. Interacts with Helicobacter pylori toxin vacA. Isoform 4 interacts with FHOD1. Interacts with FASLG. Interacts with TMIGD2.

Subcellular location. Nucleus.

Tissue specificity. Highest expression in heart, brain, skeletal muscle, kidney and liver. Lower levels in placenta, lung, small intestine and leukocytes. Weak expression in colon, thymus and spleen.

Disease relevance. A chromosomal aberration involving NCKIPSD/AF3p21 is found in therapy-related leukemia. Translocation t(3;11)(p21;q23) with KMT2A/MLL1.

Miscellaneous. Found in a brain affected by Alzheimer disease. May be due to intron retention.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9NZQ3-1	1	yes
Q9NZQ3-2	2
Q9NZQ3-3	3
Q9NZQ3-4	4, WISH-B
Q9NZQ3-5	5

RefSeq proteins (2): NP_057537, NP_909119 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR018556	SPIN90/Ldb17_LRD	Domain
IPR030125	SPIN90/Ldb17	Family
IPR035514	SPIN90_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily

Pfam: PF00018, PF09431

UniProt features (46 total): helix 24, splice variant 6, modified residue 3, compositionally biased region 3, sequence variant 2, region of interest 2, chain 1, domain 1, turn 1, strand 1, short sequence motif 1, site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6DED	X-RAY DIFFRACTION	2.2
9I2B	ELECTRON MICROSCOPY	3
6DEE	X-RAY DIFFRACTION	3.04
9M64	ELECTRON MICROSCOPY	3.4
9M5E	ELECTRON MICROSCOPY	3.55
6DEC	X-RAY DIFFRACTION	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZQ3-F1	76.48	0.50

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): 57–58 (breakpoint for translocation to form kmt2a/mll1-af3p21 oncogene)

Post-translational modifications (3): 181, 294, 120

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-5663205	Infectious disease
R-HSA-9658195	Leishmania infection
R-HSA-9664407	Parasite infection
R-HSA-9664417	Leishmania phagocytosis
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 221 (showing top): MORF_RAGE, GGGACCA_MIR133A_MIR133B, MORF_FLT1, CAR_TNFRSF25, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_SYNAPSE_ASSEMBLY, MORF_BRCA1, AAGCCAT_MIR135A_MIR135B, MORF_ATRX, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, TAL1ALPHAE47_01, MORF_ESR1, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (4): endocytosis (GO:0006897), cytoskeleton organization (GO:0007010), positive regulation of neuron projection development (GO:0010976), regulation of postsynapse assembly (GO:0150052)

GO Molecular Function (4): cytoskeletal protein binding (GO:0008092), SH3 domain binding (GO:0017124), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), cytosol (GO:0005829), intermediate filament (GO:0005882), plasma membrane (GO:0005886), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), nucleus (GO:0005634), COP9 signalosome (GO:0008180)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Fcgamma receptor (FCGR) dependent phagocytosis	1
RHO GTPase Effectors	1
Leishmania phagocytosis	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Innate Immune System	1
Disease	1
Parasitic Infection Pathways	1
Leishmania infection	1
Parasite infection	1
Signal Transduction	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
organelle organization	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
protein binding	1
protein domain specific binding	1
protein-containing complex binding	1
binding	1
nuclear lumen	1
cytoplasm	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCKIPSD	NCK1	P16333	980
NCKIPSD	WAS	P42768	836
NCKIPSD	WASL	O00401	785
NCKIPSD	FYN	P06241	732
NCKIPSD	SRC	P12931	662
NCKIPSD	PALLD	Q8WX93	656
NCKIPSD	DIAPH3	Q9NSV4	654
NCKIPSD	DLG4	P78352	560
NCKIPSD	ARHGEF7	Q14155	554
NCKIPSD	SAMD10	Q9BYL1	504
NCKIPSD	IDUA	P35475	473
NCKIPSD	UBXN2B	Q14CS0	462
NCKIPSD	AVPI1	Q5T686	455
NCKIPSD	NCKAP5L	Q9HCH0	433
NCKIPSD	ALKBH7	Q9BT30	432

IntAct

75 interactions, top by confidence:

A	B	Type	Score
NCKIPSD	BAIAP2	psi-mi:“MI:0915”(physical association)	0.680
BAIAP2	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.680
PSMD9	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.670
NCKIPSD	PSMD9	psi-mi:“MI:0915”(physical association)	0.670
NCK2	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.660
NCKIPSD	GEMIN2	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
Pacsin1	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.630
NCKIPSD	Pacsin1	psi-mi:“MI:0915”(physical association)	0.630
Diaph3	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.610
NCKIPSD	Diaph3	psi-mi:“MI:0915”(physical association)	0.610
Diaph3	NCKIPSD	psi-mi:“MI:0403”(colocalization)	0.610
NCKIPSD	Diaph3	psi-mi:“MI:0407”(direct interaction)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
FYN	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.570
NCKIPSD	FYN	psi-mi:“MI:0915”(physical association)	0.570
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
NCKIPSD	SORBS3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (192): NCKIPSD (Two-hybrid), NCKIPSD (Two-hybrid), DMRTB1 (Two-hybrid), NCKIPSD (Two-hybrid), NCKIPSD (Two-hybrid), NCKIPSD (Two-hybrid), NCKIPSD (Proximity Label-MS), NCKIPSD (Affinity Capture-MS), NCKIPSD (Affinity Capture-MS), NCKIPSD (Affinity Capture-MS), NCKIPSD (Affinity Capture-MS), NCKIPSD (Affinity Capture-MS), NCKIPSD (Affinity Capture-MS), NCKIPSD (Affinity Capture-MS), NCKIPSD (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PJB7, A0A1L8HX76, A6QR40, O08764, O60294, O95382, P10938, P70218, P97452, Q12851, Q14137, Q15334, Q16586, Q28686, Q32P44, Q3TJ91, Q499N3, Q499U2, Q4KLI9, Q561R2, Q562C2, Q5RBH8, Q5RCX2, Q61161, Q6AY79, Q6F5E8, Q6P1M3, Q6V7V2, Q7SZE3, Q7TMC8, Q80Y17, Q8BYZ7, Q8C3I8, Q8C6B2, Q8CHW4, Q8K4K5, Q8MKF0, Q8N0W3, Q8VC03, Q91WI7

Diamond homologs: Q9ESJ4, Q9NZQ3, A0JNB0, A1Y2K1, G5EE56, P06241, P39688, Q05876, Q62844

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MAPK3	up-regulates	NCKIPSD	phosphorylation
NCKIPSD	unknown	NCK1	binding
SRC	“up-regulates activity”	NCKIPSD	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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	106.2×	6e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	93.7×	1e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	93.7×	1e-09
Activation of BH3-only proteins	6	69.3×	6e-09
RHO GTPases activate PKNs	7	51.6×	2e-09
RHO GTPases Activate WASPs and WAVEs	7	51.6×	2e-09
Parasite infection	6	48.3×	5e-08
Leishmania phagocytosis	6	48.3×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	33.9×	1e-04
positive regulation of actin filament polymerization	5	30.6×	1e-04
cellular response to type II interferon	7	27.0×	4e-06
intracellular protein localization	6	11.6×	1e-03
intracellular signal transduction	8	5.7×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2123 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48674575:T:TA	donor_gain	1.0000
3:48674743:CGCAG:C	acceptor_gain	1.0000
3:48678555:T:TA	donor_gain	1.0000
3:48678875:ACC:A	donor_gain	1.0000
3:48678875:ACCC:A	donor_gain	1.0000
3:48678876:CCC:C	donor_gain	1.0000
3:48678876:CCCC:C	donor_gain	1.0000
3:48678878:C:CA	donor_gain	1.0000
3:48678967:CAG:C	acceptor_gain	1.0000
3:48678970:C:CC	acceptor_gain	1.0000
3:48679182:CT:C	acceptor_gain	1.0000
3:48679184:C:CC	acceptor_gain	1.0000
3:48679454:TGGT:T	acceptor_gain	1.0000
3:48679458:C:CC	acceptor_gain	1.0000
3:48679459:T:A	acceptor_loss	1.0000
3:48679573:AC:A	donor_gain	1.0000
3:48679574:CC:C	donor_gain	1.0000
3:48679574:CCCTG:C	donor_gain	1.0000
3:48679798:TA:T	donor_loss	1.0000
3:48679799:A:AC	donor_gain	1.0000
3:48679799:AC:A	donor_gain	1.0000
3:48679800:C:CA	donor_loss	1.0000
3:48679800:C:CC	donor_gain	1.0000
3:48679800:CC:C	donor_gain	1.0000
3:48679800:CCA:C	donor_gain	1.0000
3:48679800:CCAT:C	donor_gain	1.0000
3:48679883:TCAGT:T	acceptor_gain	1.0000
3:48679884:CAGT:C	acceptor_gain	1.0000
3:48679884:CAGTC:C	acceptor_gain	1.0000
3:48679885:AGT:A	acceptor_gain	1.0000

AlphaMissense

4645 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48679604:A:G	L487P	0.999
3:48680072:A:G	L417P	0.999
3:48680121:A:G	W401R	0.999
3:48680121:A:T	W401R	0.999
3:48681432:A:G	L316P	0.999
3:48682547:A:G	L96P	0.999
3:48680060:A:G	L421P	0.998
3:48680119:C:A	W401C	0.998
3:48680119:C:G	W401C	0.998
3:48680156:A:G	L389P	0.998
3:48680177:A:G	L382P	0.998
3:48681378:G:T	A334D	0.998
3:48682535:C:G	R100P	0.998
3:48679616:A:G	L483P	0.997
3:48679685:A:G	L460P	0.997
3:48679809:A:C	Y448D	0.997
3:48680081:A:G	L414P	0.997
3:48681379:C:G	A334P	0.997
3:48681417:C:G	R321P	0.997
3:48682972:A:T	I71N	0.997
3:48682976:C:G	A70P	0.997
3:48685737:A:G	F24S	0.997
3:48674744:G:T	R657S	0.996
3:48679616:A:C	L483R	0.996
3:48679682:A:G	L461P	0.996
3:48679713:C:T	E451K	0.996
3:48680106:C:G	D406H	0.996
3:48681312:A:T	V356D	0.996
3:48682906:A:G	L93P	0.996
3:48674665:A:G	L683P	0.995

dbSNP variants (sampled 300 via entrez): RS1001191133 (3:48678107 A>G), RS1001677706 (3:48682710 A>G,T), RS1001707424 (3:48682838 T>A,C), RS1001784527 (3:48676903 T>A), RS1002009860 (3:48683945 A>G), RS1002079021 (3:48677182 A>G), RS1002089331 (3:48683288 T>C), RS1002364612 (3:48677552 A>G), RS1002521779 (3:48678386 C>A), RS1003056498 (3:48687809 G>A), RS1003085738 (3:48681920 T>C), RS1003615774 (3:48684787 G>T), RS1003689416 (3:48685004 T>C), RS1003718757 (3:48685303 G>A), RS1004026485 (3:48686371 C>T)

Disease associations

OMIM: gene MIM:606671 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST004902_19	Parkinson’s disease	9.000000e-09
GCST005316_125	Intelligence (MTAG)	9.000000e-12
GCST008465_1	Anorexia nervosa	7.000000e-15
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST011365_60	Myocardial infarction	5.000000e-11
GCST012228_56	Waist-hip index	1.000000e-08
GCST90020024_1145	A body shape index	2.000000e-14
GCST90020029_1177	Waist circumference adjusted for body mass index	5.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004346	neuroimaging measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Caffeine	decreases phosphorylation	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TA08	HAP1 NCKIPSD (-) 1	Cancer cell line	Male
CVCL_TA09	HAP1 NCKIPSD (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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