NEDD1

Summary

NEDD1 (NEDD1 gamma-tubulin ring complex targeting factor, HGNC:7723) is a protein-coding gene on chromosome 12q23.1, encoding Protein NEDD1 (Q8NHV4). Required for mitosis progression. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

Predicted to enable gamma-tubulin binding activity. Predicted to be involved in microtubule nucleation and mitotic cell cycle. Located in centrosome; cytosol; and nuclear lumen.

Source: NCBI Gene 121441 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 107 total
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_152905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7723
Approved symbol	NEDD1
Name	NEDD1 gamma-tubulin ring complex targeting factor
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Aliases	GCP-WD, TUBGCP7
Ensembl gene	ENSG00000139350
Ensembl biotype	protein_coding
OMIM	600372
Entrez	121441

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000266742, ENST00000411739, ENST00000429527, ENST00000457368, ENST00000553609, ENST00000554226, ENST00000555114, ENST00000555806, ENST00000557092, ENST00000557400, ENST00000557454, ENST00000557478, ENST00000557644, ENST00000718088, ENST00000891025, ENST00000891026, ENST00000891027, ENST00000891028, ENST00000932014, ENST00000932015, ENST00000968008, ENST00000968009, ENST00000968010, ENST00000968011, ENST00000968012

RefSeq mRNA: 4 — MANE Select: NM_152905 NM_001135175, NM_001135176, NM_001135177, NM_152905

CCDS: CCDS44955, CCDS44956, CCDS9063

Canonical transcript exons

ENST00000266742 — 16 exons

Exon	Start	End
ENSE00000937668	96936611	96936812
ENSE00000937669	96937198	96937393
ENSE00000937670	96940409	96940537
ENSE00000937671	96942577	96942624
ENSE00000937672	96943560	96943762
ENSE00000937673	96944639	96944795
ENSE00000937674	96945693	96945849
ENSE00000937675	96951432	96951498
ENSE00001429341	96907604	96907856
ENSE00003475313	96909752	96909895
ENSE00003484479	96912723	96912817
ENSE00003560122	96934976	96935205
ENSE00003611642	96917621	96917737
ENSE00003681334	96919985	96920125
ENSE00003718542	96951949	96953780
ENSE00003901975	96907257	96907300

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 98.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8910 / max 171.3050, expressed in 1775 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127489	12.8549	1775
127490	0.0188	7
127491	0.0173	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.87	gold quality
oocyte	CL:0000023	98.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.64	gold quality
biceps brachii	UBERON:0001507	95.62	gold quality
sperm	CL:0000019	95.60	gold quality
oviduct epithelium	UBERON:0004804	95.42	gold quality
vastus lateralis	UBERON:0001379	95.03	gold quality
quadriceps femoris	UBERON:0001377	94.65	gold quality
deltoid	UBERON:0001476	94.38	gold quality
buccal mucosa cell	CL:0002336	94.17	gold quality
ventricular zone	UBERON:0003053	92.95	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.64	gold quality
skeletal muscle tissue	UBERON:0001134	92.61	gold quality
tibialis anterior	UBERON:0001385	92.60	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.22	gold quality
muscle tissue	UBERON:0002385	90.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.68	gold quality
endothelial cell	CL:0000115	90.22	gold quality
calcaneal tendon	UBERON:0003701	90.14	gold quality
muscle organ	UBERON:0001630	87.98	gold quality
skeletal muscle organ	UBERON:0014892	87.98	gold quality
epithelial cell of pancreas	CL:0000083	87.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.69	gold quality
skin of hip	UBERON:0001554	87.39	gold quality
germinal epithelium of ovary	UBERON:0001304	87.34	gold quality
epithelium of nasopharynx	UBERON:0001951	86.58	gold quality
muscle of leg	UBERON:0001383	86.34	gold quality
smooth muscle tissue	UBERON:0001135	86.13	gold quality
ileal mucosa	UBERON:0000331	85.94	silver quality
ganglionic eminence	UBERON:0004023	85.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

113 targeting NEDD1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6768-5P	99.92	67.36	1942

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 13)

• GCP-WD (NEDD1) broadly mediates targeting of the gamma-tubulin ring complex to sites of microtubule nucleation and to the mitotic spindle, which is essential for spindle formation. (PMID:16378099)
• The NEED1 protein was characterized and its function in centriole duplication and spindle assembly determined. (PMID:16461362)
• FAM29A promotes microtubule amplification via recruitment of the NEDD1-gamma-tubulin complex to the mitotic spindle. (PMID:19029337)
• Data propose NEDD1 may be a promising target for controlling cell proliferation, in particular if targeted in combination with Plk1 inhibitors. (PMID:19243593)
• Data suggest that sequential phosphorylation of Nedd1 by Cdk1 and Plk1 plays a role in targeting gamma tubulin ring complex to the centrosome by promoting the interaction of Nedd1 with the gammaTuRC component gamma-tubulin, during mitosis. (PMID:19509060)
• a direct interaction with NEDD1 regulates gamma-tubulin recruitment to the centrosome (PMID:20224777)
• Data suggest that the NEDD1/gamma-tubulin interaction is finely tuned by multiple phosphorylation events in the S557-S574 region and is critical for spindle assembly. (PMID:22595525)
• Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of gamma-tubulin to the centrosome in mitotic cells. (PMID:22818914)
• The mice treated with small interfering (si) RNA targeting NEDD1 by the atelocollagen-mediated delivery system showed a significantly prolonged survival in a xenograft model of human gastric cancer. (PMID:23106787)
• One important function of Aurora A in mitotic cells is to promote microtubule nucleation around the chromatin by phosphorylating NEDD1, and thereby to promote functional spindle assembly. (PMID:23273898)
• Authors show here that the expression of a NEDD1 isoform mimicking phosphorylation by Aurora A is sufficient to restore microtubule nucleation in the midzone under conditions of Aurora A inhibition. (PMID:31028180)
• PLK4-phosphorylated NEDD1 facilitates cartwheel assembly and centriole biogenesis initiations. (PMID:33351100)
• NEDD1-S411 phosphorylation plays a critical function in the coordination of microtubule nucleation during mitosis. (PMID:36318115)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nedd1	ENSMUSG00000019988
rattus_norvegicus	Nedd1	ENSRNOG00000004011

Paralogs (26): PAFAH1B1 (ENSG00000007168), SNRNP40 (ENSG00000060688), WDR62 (ENSG00000075702), WDR7 (ENSG00000091157), TBL2 (ENSG00000106638), PAK1IP1 (ENSG00000111845), WDR75 (ENSG00000115368), DCAF4 (ENSG00000119599), DAW1 (ENSG00000123977), TEP1 (ENSG00000129566), AHI1 (ENSG00000135541), WDR38 (ENSG00000136918), MAPKBP1 (ENSG00000137802), POC1B (ENSG00000139323), COP1 (ENSG00000143207), WDR17 (ENSG00000150627), WDR43 (ENSG00000163811), POC1A (ENSG00000164087), WDR88 (ENSG00000166359), WDR81 (ENSG00000167716), DCAF4L2 (ENSG00000176566), DCAF4L1 (ENSG00000182308), WDR27 (ENSG00000184465), NWD1 (ENSG00000188039), WDR5 (ENSG00000196363), WDR5B (ENSG00000196981)

Protein

Protein identifiers

Protein NEDD1 — Q8NHV4 (reviewed: Q8NHV4)

Alternative names: Neural precursor cell expressed developmentally down-regulated protein 1

All UniProt accessions (6): Q8NHV4, G3V2M9, G3V2S2, G3V2V3, G3V4I9, G3V4L2

UniProt curated annotations — full annotation on UniProt →

Function. Required for mitosis progression. Promotes the nucleation of microtubules from the spindle.

Subunit / interactions. Interacts with FAM29A. Interacts with HSPA1A and HSPA1B. Interacts with gamma-tubulin in a HSPA1A/B-dependent manner.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Post-translational modifications. During mitosis, prior phosphorylation on Thr-550 by CDK1 promotes subsequent phosphorylation by PLK1 on Thr-382, Ser-397, Ser-426 and Ser-637. Phosphorylated NEDD1 can interact with gamma-tubulin for targeting the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NHV4-1	1	yes
Q8NHV4-2	2
Q8NHV4-3	3

RefSeq proteins (4): NP_001128647, NP_001128648, NP_001128649, NP_690869* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR052818	NEDD1_Spindle_Assembly	Family

Pfam: PF00400

UniProt features (26 total): modified residue 9, repeat 8, sequence conflict 3, region of interest 2, splice variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9QVN	ELECTRON MICROSCOPY	4.7
9QVM	ELECTRON MICROSCOPY	6.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHV4-F1	66.56	0.36

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 (9): 325, 382, 397, 411, 426, 468, 516, 550, 637

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 155 (showing top): WANG_CLIM2_TARGETS_UP, GOBP_MICROTUBULE_NUCLEATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, ATF1_Q6, GOCC_CENTROSOME, GOBP_MITOTIC_CELL_CYCLE, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, IK3_01, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ATF_01, GOBP_MICROTUBULE_POLYMERIZATION, GOCC_SPINDLE, GOCC_CENTRIOLE, GOCC_APICAL_PART_OF_CELL

GO Biological Process (3): mitotic cell cycle (GO:0000278), microtubule nucleation (GO:0007020), cell division (GO:0051301)

GO Molecular Function (2): gamma-tubulin binding (GO:0043015), protein binding (GO:0005515)

GO Cellular Component (11): pericentriolar material (GO:0000242), spindle pole (GO:0000922), fibrillar center (GO:0001650), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), ciliary basal body (GO:0036064), apical part of cell (GO:0045177), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1
M Phase	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
microtubule organizing center	3
intracellular membraneless organelle	2
cell cycle	1
mitotic nuclear division	1
microtubule cytoskeleton organization	1
microtubule polymerization	1
cellular process	1
tubulin binding	1
binding	1
centrosome	1
spindle	1
nucleolus	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
cytoplasm	1
cilium	1

Protein interactions and networks

STRING

1188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEDD1	HAUS6	Q7Z4H7	977
NEDD1	TUBGCP4	Q9UGJ1	899
NEDD1	MZT1	Q08AG7	894
NEDD1	TUBGCP3	Q96CW5	875
NEDD1	TUBGCP5	Q96RT8	871
NEDD1	TUBGCP6	Q96RT7	853
NEDD1	PCNT	O95613	853
NEDD1	CEP192	Q8TEP8	839
NEDD1	PLK1	P53350	834
NEDD1	PLK4	O00444	802
NEDD1	TUBG1	P23258	786
NEDD1	MZT2A	Q6P582	754
NEDD1	HAUS5	O94927	739
NEDD1	CDK5RAP2	Q96SN8	720
NEDD1	HAUS3	Q68CZ6	706

IntAct

151 interactions, top by confidence:

A	B	Type	Score
CEP97	CCP110	psi-mi:“MI:2364”(proximity)	0.950
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
FBXO28	TRAF5	psi-mi:“MI:0914”(association)	0.740
PAAT	CLTC	psi-mi:“MI:0914”(association)	0.740
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
PDCL3	PEX7	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
Mzt2	TUBG1	psi-mi:“MI:0914”(association)	0.560
Haus4	HAUS5	psi-mi:“MI:0915”(physical association)	0.560
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
NEDD1	MZT2A	psi-mi:“MI:0914”(association)	0.530
PPP1R13B	CCDC85C	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530
GPN2	POLR2C	psi-mi:“MI:0914”(association)	0.530

BioGRID (320): NEDD1 (Affinity Capture-MS), NEDD1 (Affinity Capture-MS), NEDD1 (Affinity Capture-MS), NEDD1 (Affinity Capture-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS), NEDD1 (Proximity Label-MS)

ESM2 similar proteins: A0A1P8AW69, A8MQL1, A9QM73, B0F9L7, B3H5K9, E1C213, F4I1T7, F4I6M4, F4I7C7, F4IK92, F4JBP3, F4JP52, F4JTJ2, F4JUQ2, F4KB17, M1BJF6, O22864, O80386, P33215, Q0JDM0, Q0WPF2, Q3B7M6, Q5CCK4, Q60GC1, Q6DGG9, Q6NPP4, Q6NPR6, Q7ZXT3, Q84JU6, Q8GSA7, Q8GUL1, Q8H0T9, Q8H1Q5, Q8LPQ9, Q8NHV4, Q8RX78, Q8RY18, Q9C5H4, Q9C9U5, Q9FPR3

Diamond homologs: C4JPW9, F1LTR1, O13923, O14021, O22466, O22467, O22468, O22469, O22607, O93377, O94244, O94423, P0CS36, P0CS37, P26309, P39984, P90916, P90917, Q09028, Q10G81, Q16576, Q24572, Q28D01, Q2UA71, Q2YDS1, Q3B7M6, Q3MHL3, Q3SWX8, Q4I7L0, Q4P553, Q4R304, Q4WEI5, Q54SD4, Q55E54, Q59RH5, Q5M7K4, Q5M7T1, Q5R654, Q5RF92, Q5SP67

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
HAUS6	“up-regulates activity”	NEDD1	binding
NEDD1	“up-regulates activity”	“g-TuRC complex”	binding
“HAUS complex”	“up-regulates activity”	NEDD1	relocalization
AURKA	“up-regulates activity”	NEDD1	phosphorylation
CDK1	“up-regulates activity”	NEDD1	phosphorylation
PLK1	“up-regulates activity”	NEDD1	phosphorylation
NEK9	“up-regulates activity”	NEDD1	phosphorylation
PLK4	“up-regulates activity”	NEDD1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 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
Prefoldin mediated transfer of substrate to CCT/TriC	8	30.9×	9e-09
Recruitment of mitotic centrosome proteins and complexes	19	25.3×	1e-19
Loss of Nlp from mitotic centrosomes	15	23.3×	6e-15
Loss of proteins required for interphase microtubule organization from the centrosome	15	23.3×	6e-15
Recruitment of NuMA to mitotic centrosomes	20	22.9×	1e-19
AURKA Activation by TPX2	15	22.4×	1e-14
Anchoring of the basal body to the plasma membrane	20	22.2×	1e-19
Formation of tubulin folding intermediates by CCT/TriC	5	20.7×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	7	37.2×	2e-07
regulation of mitotic spindle organization	5	30.5×	6e-05
microtubule nucleation	6	27.1×	1e-05
cytoplasmic microtubule organization	7	17.4×	2e-05
spindle assembly	5	16.1×	7e-04
centrosome cycle	5	12.2×	2e-03
non-motile cilium assembly	5	10.5×	4e-03
protein folding	14	10.5×	6e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2793 predictions. Top by Δscore:

Variant	Effect	Δscore
12:96934974:A:AG	acceptor_gain	1.0000
12:96934975:G:GA	acceptor_gain	1.0000
12:96934975:GTCT:G	acceptor_gain	1.0000
12:96935203:GAA:G	donor_gain	1.0000
12:96935206:G:GG	donor_gain	1.0000
12:96936607:A:AG	acceptor_gain	1.0000
12:96936607:AAAG:A	acceptor_gain	1.0000
12:96936608:A:G	acceptor_gain	1.0000
12:96936610:GGCTA:G	acceptor_gain	1.0000
12:96936811:AGGT:A	donor_loss	1.0000
12:96936812:GGTGA:G	donor_loss	1.0000
12:96937186:A:AG	acceptor_gain	1.0000
12:96937191:A:AG	acceptor_gain	1.0000
12:96937192:T:G	acceptor_gain	1.0000
12:96937194:TCAGT:T	acceptor_loss	1.0000
12:96937195:CA:C	acceptor_loss	1.0000
12:96937196:A:AG	acceptor_gain	1.0000
12:96937197:G:GA	acceptor_gain	1.0000
12:96937197:GT:G	acceptor_gain	1.0000
12:96937197:GTC:G	acceptor_gain	1.0000
12:96937197:GTCA:G	acceptor_gain	1.0000
12:96937197:GTCAA:G	acceptor_gain	1.0000
12:96937390:GCAG:G	donor_gain	1.0000
12:96937391:C:T	donor_gain	1.0000
12:96937394:G:GC	donor_loss	1.0000
12:96937395:T:G	donor_loss	1.0000
12:96940407:A:G	acceptor_gain	1.0000
12:96945689:TTA:T	acceptor_loss	1.0000
12:96945690:TA:T	acceptor_loss	1.0000
12:96945691:A:AG	acceptor_gain	1.0000

AlphaMissense

4346 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:96909808:T:A	W17R	0.999
12:96909808:T:C	W17R	0.999
12:96917669:A:C	S94R	0.999
12:96917671:C:A	S94R	0.999
12:96917671:C:G	S94R	0.999
12:96952016:T:C	L649P	0.999
12:96909782:C:A	A8D	0.998
12:96909883:T:A	W42R	0.998
12:96909883:T:C	W42R	0.998
12:96917691:T:A	V101D	0.998
12:96920040:C:A	A135D	0.998
12:96920042:T:C	S136P	0.998
12:96936688:G:A	G266E	0.998
12:96912768:T:A	V61D	0.997
12:96917699:T:A	W104R	0.997
12:96917699:T:C	W104R	0.997
12:96935024:A:C	S180R	0.997
12:96935026:T:A	S180R	0.997
12:96935026:T:G	S180R	0.997
12:96935054:T:A	W190R	0.997
12:96935054:T:C	W190R	0.997
12:96935162:G:C	G226R	0.997
12:96935169:A:T	D228V	0.997
12:96936700:G:T	G270V	0.997
12:96951473:T:G	M618R	0.997
12:96952019:G:C	R650P	0.997
12:96935021:G:C	G179R	0.996
12:96935022:G:A	G179D	0.996
12:96935168:G:C	D228H	0.996
12:96936687:G:A	G266R	0.996

dbSNP variants (sampled 300 via entrez): RS1000028426 (12:96932607 A>C), RS1000088472 (12:96932019 A>G,T), RS1000120968 (12:96924618 A>T), RS1000166492 (12:96915543 A>G), RS1000220189 (12:96932862 A>T), RS1000224780 (12:96926451 A>G), RS1000308623 (12:96926041 T>C), RS1000362817 (12:96938805 T>C,G), RS1000368850 (12:96919070 A>G), RS1000483132 (12:96940089 G>T), RS1000484696 (12:96919323 G>A,C), RS1000527030 (12:96927148 G>A), RS1000559018 (12:96924531 A>T), RS1000654971 (12:96931826 T>TA), RS1000697347 (12:96938208 T>C)

Disease associations

OMIM: gene MIM:600372 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001585_18	Breast size	1.000000e-06
GCST002268_11	Autism	2.000000e-06
GCST002932_5	Manganese levels	6.000000e-06
GCST006148_10	Frontotemporal dementia with GRN mutation	2.000000e-06
GCST006154_5	Frontotemporal dementia	5.000000e-06
GCST007324_48	Adventurousness	4.000000e-08
GCST011517_5	joint destruction in rheumatoid arthritis (rapid vs slow)	2.000000e-06
GCST011921_1	Obstructive sleep apnea (BMI adjusted)	1.000000e-09
GCST012481_8	Cerebral amyloid angiopathy in Alzheimer’s disease	6.000000e-06
GCST012481_9	Cerebral amyloid angiopathy in Alzheimer’s disease	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0005413	joint damage measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Air Pollutants	decreases expression, increases abundance, affects cotreatment	2
Valproic Acid	increases expression, decreases methylation, affects cotreatment	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
beta-lapachone	decreases expression, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Latex	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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