SCIN

Summary

SCIN (scinderin, HGNC:21695) is a protein-coding gene on chromosome 7p21.3, encoding Scinderin (Q9Y6U3). Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane.

SCIN is a Ca(2+)-dependent actin-severing and -capping protein (Zunino et al., 2001 [PubMed 11568009]).

Source: NCBI Gene 85477 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 150 total
• MANE Select transcript: NM_001112706

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21695
Approved symbol	SCIN
Name	scinderin
Location	7p21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1905
Ensembl gene	ENSG00000006747
Ensembl biotype	protein_coding
OMIM	613416
Entrez	85477

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000297029, ENST00000341757, ENST00000417018, ENST00000436854, ENST00000473722, ENST00000476649, ENST00000486980, ENST00000518849, ENST00000519209, ENST00000523729, ENST00000906404, ENST00000906405, ENST00000955153, ENST00000955154

RefSeq mRNA: 2 — MANE Select: NM_001112706 NM_001112706, NM_033128

CCDS: CCDS47545, CCDS47546

Canonical transcript exons

ENST00000297029 — 16 exons

Exon	Start	End
ENSE00000671859	12578064	12578218
ENSE00000671861	12581060	12581221
ENSE00000831784	12629101	12629222
ENSE00000831785	12636045	12636135
ENSE00000831786	12640347	12640517
ENSE00000976151	12644138	12644315
ENSE00001750790	12652588	12660182
ENSE00001893862	12570720	12570985
ENSE00003482128	12625010	12625142
ENSE00003489315	12644584	12644705
ENSE00003533962	12625762	12625850
ENSE00003568669	12649467	12649544
ENSE00003581251	12626584	12626799
ENSE00003586547	12604514	12604663
ENSE00003659697	12651841	12651901
ENSE00003688011	12622801	12622893

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 95.26.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0035 / max 145.9686, expressed in 606 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77281	3.6701	577
77280	0.1756	121
77279	0.1317	72
77284	0.0223	7
77285	0.0037	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	95.26	gold quality
tibia	UBERON:0000979	95.09	gold quality
renal medulla	UBERON:0000362	94.61	gold quality
metanephros cortex	UBERON:0010533	94.58	gold quality
duodenum	UBERON:0002114	92.77	gold quality
calcaneal tendon	UBERON:0003701	91.65	gold quality
esophagus squamous epithelium	UBERON:0006920	91.38	gold quality
mucosa of transverse colon	UBERON:0004991	91.16	gold quality
adult mammalian kidney	UBERON:0000082	91.03	gold quality
buccal mucosa cell	CL:0002336	90.59	silver quality
palpebral conjunctiva	UBERON:0001812	90.33	gold quality
epithelium of esophagus	UBERON:0001976	90.25	gold quality
oral cavity	UBERON:0000167	89.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.63	gold quality
right uterine tube	UBERON:0001302	89.51	gold quality
rectum	UBERON:0001052	89.08	gold quality
placenta	UBERON:0001987	88.52	gold quality
colonic mucosa	UBERON:0000317	87.69	gold quality
lower esophagus mucosa	UBERON:0035834	87.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.38	gold quality
secondary oocyte	CL:0000655	86.57	gold quality
kidney	UBERON:0002113	86.55	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.27	gold quality
esophagus mucosa	UBERON:0002469	85.90	gold quality
jejunum	UBERON:0002115	85.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.88	gold quality
oocyte	CL:0000023	84.82	gold quality
small intestine	UBERON:0002108	84.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.62	gold quality
amniotic fluid	UBERON:0000173	84.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	751.19
E-CURD-119	yes	33.74
E-HCAD-10	yes	27.31
E-MTAB-5061	yes	13.42
E-CURD-114	yes	10.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting SCIN, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-6780A-3P	98.42	67.49	1518

Literature-anchored findings (GeneRIF, showing 12)

• calcium binding to the N terminus of adseverin dominates the activation process to expose the F-actin binding site on A2 (PMID:19666531)
• These results suggest that SCIN plays an important role in the proliferation of prostate cancer cells and lentivirus-mediated inhibition of SCIN expression may be a potential therapeutic method for the treatment of prostate cancer (PMID:24212916)
• Scinderin expression does not correlate with prognosis in head and neck cancer. (PMID:24330498)
• Suppression of scinderin impairs proliferation and migration of gastric cancer SGC7901 cells and attenuates its epithelialmesenchymal transition process. (PMID:25174406)
• SCIN plays an important role in lung carcinoma cell proliferation (PMID:25303873)
• High levels of SCIN expression in gastric cancer tissue correlate with poor prognosis of patients. SCIN enhances the invasion and metastasis of GC cells through activating the Cdc42 pathway to increase the formation of filopodia. (PMID:27033455)
• Epistasis analysis identified a statistically significant interaction between CDC42 and SCIN SNPs which are strongly associated with CDC42 and SCIN gene expression levels and map to regulatory elements in skin cells. This interaction has important biological relevance since CDC42 and SCIN proteins have opposite effects in actin cytoskeleton organization and dynamics, which underlies melanoma cell migration and invasion. (PMID:27347659)
• Data suggest that scinderin (Scin) played a vital role in the development of developmental dysplasia of the hip (DDH). (PMID:28213129)
• Findings indicate that decreased scinderin (SCIN) expression associated with its promoter methylation is a valuable biomarker for predicting adverse prognosis in acute myeloid leukemia (AML) patients. (PMID:29457658)
• down-regulation of SCIN expression may relate with the progression of chronic myeloid leukemia (PMID:31204912)
• The AHR target gene scinderin activates the WNT pathway by facilitating the nuclear translocation of beta-catenin. (PMID:36148682)
• Scinderin Promotes Hydrogen Peroxide-induced Lens Epithelial Cell Injury in Age-related Cataract. (PMID:37936437)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	scin	ENSDARG00000010728
mus_musculus	Scin	ENSMUSG00000002565
rattus_norvegicus	Scin	ENSRNOG00000004498
drosophila_melanogaster	Gel	FBGN0010225
caenorhabditis_elegans		WBGENE00010593

Paralogs (7): CAPG (ENSG00000042493), VIL1 (ENSG00000127831), AVIL (ENSG00000135407), VILL (ENSG00000136059), GSN (ENSG00000148180), FLII (ENSG00000177731), SVIL (ENSG00000197321)

Protein

Protein identifiers

Scinderin — Q9Y6U3 (reviewed: Q9Y6U3)

Alternative names: Adseverin

All UniProt accessions (5): Q9Y6U3, C9JGB6, E5RHN8, E5RHX6, F8WBX5

UniProt curated annotations — full annotation on UniProt →

Function. Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane. Severing activity is inhibited by phosphatidylinositol 4,5-bis-phosphate (PIP2). In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+). Required for megakaryocyte differentiation, maturation, polyploidization and apoptosis with the release of platelet-like particles. Plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts. Regulates chondrocyte proliferation and differentiation. Inhibits cell proliferation and tumorigenesis. Signaling is mediated by MAPK, p38 and JNK pathways.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Podosome.

Tissue specificity. Expressed in megakaryocytes.

Miscellaneous. Scinderin comes from the latine world ‘scincere’, meaning ’to cut’.

Similarity. Belongs to the villin/gelsolin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y6U3-1	1	yes
Q9Y6U3-2	2
Q9Y6U3-3	3

RefSeq proteins (2): NP_001106177, NP_149119 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007122	Villin/Gelsolin	Family
IPR007123	Gelsolin-like_dom	Domain
IPR029006	ADF-H/Gelsolin-like_dom_sf	Homologous_superfamily
IPR036180	Gelsolin-like_dom_sf	Homologous_superfamily

Pfam: PF00626

UniProt features (95 total): strand 38, helix 19, binding site 8, repeat 6, sequence variant 5, turn 5, splice variant 3, mutagenesis site 3, sequence conflict 3, modified residue 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5A1M	X-RAY DIFFRACTION	1.81
5A1K	X-RAY DIFFRACTION	2.9
3FG6	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6U3-F1	83.93	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.

Ligand- & substrate-binding residues (8): 138–146; 538; 539; 562; 643; 644; 666; 112–119

Post-translational modifications (2): 102, 599

Mutagenesis-validated functional residues (3):

Position	Phenotype
310	increases calcium-independent actin-severing activity.
314	increases calcium-independent actin-severing activity.
455	loss of actin-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 267 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_BCELL_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION

GO Biological Process (14): central nervous system development (GO:0007417), actin polymerization or depolymerization (GO:0008154), negative regulation of cell population proliferation (GO:0008285), calcium-ion regulated exocytosis (GO:0017156), cell projection assembly (GO:0030031), regulation of chondrocyte differentiation (GO:0032330), positive regulation of apoptotic process (GO:0043065), actin nucleation (GO:0045010), positive regulation of megakaryocyte differentiation (GO:0045654), actin filament severing (GO:0051014), barbed-end actin filament capping (GO:0051016), positive regulation of secretion (GO:0051047), positive regulation of actin nucleation (GO:0051127), actin filament capping (GO:0051693)

GO Molecular Function (8): phosphatidylserine binding (GO:0001786), actin binding (GO:0003779), calcium ion binding (GO:0005509), 1-phosphatidylinositol binding (GO:0005545), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), actin filament binding (GO:0051015), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): podosome (GO:0002102), cytoplasm (GO:0005737), brush border (GO:0005903), cell cortex (GO:0005938), actin cytoskeleton (GO:0015629), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin filament organization	2
phospholipid binding	2
cellular anatomical structure	2
nervous system development	1
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulated exocytosis	1
cellular component assembly	1
cell projection organization	1
chondrocyte differentiation	1
regulation of cell differentiation	1
regulation of cartilage development	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
megakaryocyte differentiation	1
positive regulation of myeloid cell differentiation	1
regulation of megakaryocyte differentiation	1
actin filament-based process	1
actin filament capping	1
secretion	1
regulation of secretion	1
positive regulation of transport	1
actin nucleation	1
regulation of actin nucleation	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
anion binding	1
modified amino acid binding	1
cytoskeletal protein binding	1
metal ion binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
actin binding	1
protein-containing complex binding	1
binding	1

Protein interactions and networks

STRING

2480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCIN	HCLS1	P14317	986
SCIN	CTTN	Q14247	985
SCIN	TLN1	Q9Y490	940
SCIN	WASL	O00401	937
SCIN	TLN2	Q9Y4G6	936
SCIN	PFN4	Q8NHR9	892
SCIN	PFN3	P60673	879
SCIN	VCL	P18206	878
SCIN	GC	P02774	878
SCIN	PFN1	P07737	874
SCIN	CFL1	P23528	865
SCIN	VASP	P50552	854
SCIN	WAS	P42768	846
SCIN	CFL2	Q9Y281	844
SCIN	PXN	P49023	838

IntAct

36 interactions, top by confidence:

A	B	Type	Score
SLC30A5	SLC30A6	psi-mi:“MI:0914”(association)	0.840
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7C	SCIN	psi-mi:“MI:0915”(physical association)	0.560
SSH1	YWHAE	psi-mi:“MI:0914”(association)	0.530
TWF1	MYO1C	psi-mi:“MI:0914”(association)	0.530
TMOD1	GSN	psi-mi:“MI:0914”(association)	0.530
SCIN	OCIAD2	psi-mi:“MI:0915”(physical association)	0.400
NEK4	QSOX1	psi-mi:“MI:0914”(association)	0.350
LSP1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TMOD2	GSN	psi-mi:“MI:0914”(association)	0.350
BCL7A	DPF1	psi-mi:“MI:0914”(association)	0.350
BCL7C	DPF1	psi-mi:“MI:0914”(association)	0.350
TMOD3	MEIS2	psi-mi:“MI:0914”(association)	0.350
TMOD1	TBC1D4	psi-mi:“MI:0914”(association)	0.350
ACTR1B	DCTN3	psi-mi:“MI:0914”(association)	0.350
DAPK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
HASPIN	MYO1C	psi-mi:“MI:0914”(association)	0.350
GRB2	MYO1C	psi-mi:“MI:0914”(association)	0.350
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350
SCIN	POTEF	psi-mi:“MI:0914”(association)	0.350
TMOD3	PRPF4	psi-mi:“MI:0914”(association)	0.350
ACTB	MYO1B	psi-mi:“MI:0914”(association)	0.350
GRXCR1	VPS4B	psi-mi:“MI:0914”(association)	0.350
GPAM	SRC	psi-mi:“MI:0914”(association)	0.350
TMOD3	GSN	psi-mi:“MI:0914”(association)	0.350

BioGRID (71): SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Affinity Capture-MS), SCIN (Proximity Label-MS)

ESM2 similar proteins: A0A6B9KZ40, A8XV95, B8ATT7, O65570, O75366, O81644, O81645, O88398, O93510, P02640, P06396, P09327, P10733, P13020, P14885, P20305, P24452, P40121, Q07171, Q0J716, Q0JAD9, Q10L71, Q12792, Q17A58, Q24800, Q27319, Q28046, Q28372, Q29261, Q29297, Q298X4, Q3SX14, Q3SZP7, Q5R7N2, Q5RJR2, Q5ZIV9, Q60604, Q62468, Q67U26, Q68FP1

Diamond homologs: A0A6B9KZ40, A8XV95, B8ATT7, F8WK50, O15195, O61270, O65570, O75366, O81643, O81644, O81645, O88398, O93510, P02640, P06396, P09327, P10733, P13020, P14885, P20305, P24452, P34268, P40121, Q07171, Q0J716, Q0JAD9, Q10L71, Q13045, Q21253, Q24020, Q24800, Q27319, Q28046, Q28372, Q29261, Q29297, Q3SX14, Q3SZP7, Q5ZIV9, Q60604

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
Formation of the canonical BAF (cBAF) complex	5	102.3×	3e-07
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	5	73.7×	9e-07
Regulation of MITF-M-dependent genes involved in pigmentation	5	42.8×	9e-06
Sensory processing of sound by outer hair cells of the cochlea	6	39.5×	9e-07
FCGR3A-mediated phagocytosis	5	30.2×	4e-05
Sensory processing of sound by inner hair cells of the cochlea	5	26.3×	6e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	24.9×	6e-05
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	5	19.0×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	5	80.2×	2e-06
regulation of nucleotide-excision repair	5	71.7×	2e-06
regulation of mitotic metaphase/anaphase transition	5	59.0×	3e-06
positive regulation of double-strand break repair	5	40.9×	1e-05
regulation of G1/S transition of mitotic cell cycle	5	36.5×	2e-05
actin filament organization	6	16.9×	8e-05
chromatin remodeling	6	10.4×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	130
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2594 predictions. Top by Δscore:

Variant	Effect	Δscore
7:12570981:GCTCG:G	donor_gain	1.0000
7:12570982:CTCGG:C	donor_loss	1.0000
7:12570983:TCGG:T	donor_loss	1.0000
7:12570984:CGGTA:C	donor_loss	1.0000
7:12570986:GT:G	donor_loss	1.0000
7:12570987:T:A	donor_loss	1.0000
7:12578059:TTTAG:T	acceptor_loss	1.0000
7:12578060:TTAG:T	acceptor_loss	1.0000
7:12578061:TAGGA:T	acceptor_loss	1.0000
7:12578062:AGGAA:A	acceptor_loss	1.0000
7:12578063:GGAAA:G	acceptor_gain	1.0000
7:12578166:GATA:G	donor_gain	1.0000
7:12578217:AGG:A	donor_loss	1.0000
7:12578219:G:C	donor_loss	1.0000
7:12578219:G:GG	donor_gain	1.0000
7:12581034:T:TA	acceptor_gain	1.0000
7:12581051:A:AG	acceptor_gain	1.0000
7:12581052:T:G	acceptor_gain	1.0000
7:12581055:ATCAG:A	acceptor_gain	1.0000
7:12581057:CAGGC:C	acceptor_loss	1.0000
7:12581058:A:AG	acceptor_gain	1.0000
7:12581058:AG:A	acceptor_gain	1.0000
7:12581059:G:GG	acceptor_gain	1.0000
7:12581059:GG:G	acceptor_gain	1.0000
7:12581059:GGCT:G	acceptor_gain	1.0000
7:12581217:GCACC:G	donor_gain	1.0000
7:12581218:CACC:C	donor_gain	1.0000
7:12581222:G:GG	donor_gain	1.0000
7:12604513:GGAA:G	acceptor_gain	1.0000
7:12604638:G:GT	donor_gain	1.0000

AlphaMissense

4715 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:12629221:T:A	W440R	0.998
7:12629221:T:C	W440R	0.998
7:12651850:T:A	W657R	0.998
7:12651850:T:C	W657R	0.998
7:12604526:T:A	W177R	0.996
7:12604526:T:C	W177R	0.996
7:12649504:T:C	L640S	0.996
7:12649528:T:C	L648P	0.996
7:12625136:T:A	W296R	0.995
7:12625136:T:C	W296R	0.995
7:12629108:G:C	R402P	0.995
7:12636045:G:C	W440C	0.995
7:12636045:G:T	W440C	0.995
7:12581201:T:C	F166L	0.994
7:12581203:C:A	F166L	0.994
7:12581203:C:G	F166L	0.994
7:12622886:T:C	L251P	0.994
7:12625097:T:C	F283L	0.994
7:12625099:T:A	F283L	0.994
7:12625099:T:G	F283L	0.994
7:12625142:G:C	G298R	0.994
7:12625762:G:T	G298V	0.994
7:12651857:G:A	G659D	0.994
7:12651857:G:T	G659V	0.994
7:12652622:A:C	R685S	0.994
7:12652622:A:T	R685S	0.994
7:12652695:T:A	W710R	0.994
7:12652695:T:C	W710R	0.994
7:12570979:T:A	W65R	0.993
7:12570979:T:C	W65R	0.993

dbSNP variants (sampled 300 via entrez): RS1000007695 (7:12568888 C>T), RS1000016795 (7:12607619 A>G), RS1000071705 (7:12582852 C>A), RS1000088645 (7:12607790 A>C), RS1000092388 (7:12631839 G>A,C), RS1000184670 (7:12621170 T>C), RS1000185249 (7:12578454 T>C), RS1000188207 (7:12617932 T>G), RS1000208340 (7:12648285 C>G,T), RS1000221376 (7:12616956 T>C), RS1000236771 (7:12602590 C>T), RS1000266758 (7:12658426 A>T), RS1000274066 (7:12652963 C>T), RS1000291157 (7:12580488 C>A,T), RS1000319545 (7:12658118 A>G)

Disease associations

OMIM: gene MIM:613416 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004746_14	Small cell lung carcinoma	2.000000e-06
GCST008839_188	Height	2.000000e-11
GCST009391_1037	Metabolite levels	8.000000e-06
GCST009391_1272	Metabolite levels	9.000000e-07
GCST009391_1992	Metabolite levels	5.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009775	threonine measurement
EFO:0010546	uridine measurement
EFO:0010542	ureidopropionic acid 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
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
bisphenol A	decreases expression, decreases methylation	2
trichostatin A	affects expression, increases expression	2
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	2
mercuric bromide	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
NSC 689534	affects binding, decreases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1
Aflatoxins	increases expression	1
Ethanol	increases expression	1
Benzo(a)pyrene	increases methylation	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

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