CAMSAP3

Summary

CAMSAP3 (calmodulin regulated spectrin associated protein family member 3, HGNC:29307) is a protein-coding gene on chromosome 19p13.2, encoding Calmodulin-regulated spectrin-associated protein 3 (Q9P1Y5). Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization.

Enables actin filament binding activity and microtubule minus-end binding activity. Involved in several processes, including microtubule cytoskeleton organization; regulation of organelle organization; and zonula adherens maintenance. Located in cytoplasm; microtubule cytoskeleton; and zonula adherens.

Source: NCBI Gene 57662 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 204 total
• MANE Select transcript: NM_020902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29307
Approved symbol	CAMSAP3
Name	calmodulin regulated spectrin associated protein family member 3
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Nezha, PPP1R80
Ensembl gene	ENSG00000076826
Ensembl biotype	protein_coding
OMIM	612685
Entrez	57662

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 retained_intron

ENST00000160298, ENST00000446248, ENST00000593434, ENST00000595692, ENST00000867870, ENST00000867871, ENST00000867872, ENST00000930505, ENST00000930506, ENST00000930507, ENST00000930508, ENST00000930509

RefSeq mRNA: 2 — MANE Select: NM_020902 NM_001080429, NM_020902

CCDS: CCDS42489, CCDS45947

Canonical transcript exons

ENST00000160298 — 17 exons

Exon	Start	End
ENSE00000671221	7611095	7611168
ENSE00000671227	7611517	7611586
ENSE00000671238	7611687	7613163
ENSE00000671249	7615183	7615322
ENSE00001156480	7610877	7610931
ENSE00001254471	7617752	7618304
ENSE00001405077	7610476	7610615
ENSE00001405540	7610700	7610793
ENSE00001419315	7605226	7605479
ENSE00001420335	7606271	7606393
ENSE00001426925	7606476	7606571
ENSE00001433526	7608126	7608264
ENSE00003503424	7617326	7617438
ENSE00003513964	7617543	7617661
ENSE00003622698	7616523	7616622
ENSE00003651118	7615418	7615719
ENSE00003899332	7595863	7596150

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 96.74.

FANTOM5 (CAGE): breadth broad, TPM avg 5.2855 / max 85.3454, expressed in 762 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173578	5.2855	762

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.74	gold quality
skin of abdomen	UBERON:0001416	95.60	gold quality
zone of skin	UBERON:0000014	95.25	gold quality
skin of leg	UBERON:0001511	95.11	gold quality
mucosa of transverse colon	UBERON:0004991	93.83	gold quality
right lobe of liver	UBERON:0001114	93.03	gold quality
cortical plate	UBERON:0005343	92.70	gold quality
body of pancreas	UBERON:0001150	90.97	gold quality
cerebellar hemisphere	UBERON:0002245	90.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.22	gold quality
cerebellum	UBERON:0002037	90.19	gold quality
cerebellar cortex	UBERON:0002129	90.19	gold quality
esophagus mucosa	UBERON:0002469	89.34	gold quality
duodenum	UBERON:0002114	89.05	gold quality
right lobe of thyroid gland	UBERON:0001119	88.09	gold quality
metanephros cortex	UBERON:0010533	87.85	gold quality
saliva-secreting gland	UBERON:0001044	87.46	gold quality
minor salivary gland	UBERON:0001830	87.19	gold quality
liver	UBERON:0002107	87.08	gold quality
right uterine tube	UBERON:0001302	86.72	gold quality
right frontal lobe	UBERON:0002810	86.46	gold quality
right testis	UBERON:0004534	86.28	gold quality
left lobe of thyroid gland	UBERON:0001120	86.21	gold quality
adult mammalian kidney	UBERON:0000082	86.10	gold quality
thyroid gland	UBERON:0002046	85.88	gold quality
left testis	UBERON:0004533	85.43	gold quality
primary visual cortex	UBERON:0002436	85.32	gold quality
ganglionic eminence	UBERON:0004023	85.31	gold quality
pituitary gland	UBERON:0000007	84.77	gold quality
superior frontal gyrus	UBERON:0002661	84.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting CAMSAP3, 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-4267	99.96	66.53	2368
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-1233-3P	96.81	65.44	573
HSA-MIR-4652-5P	96.46	64.22	553
HSA-MIR-3943	95.87	64.57	523
HSA-MIR-4515	95.70	65.73	716
HSA-MIR-4524B-3P	95.52	64.12	964

Literature-anchored findings (GeneRIF, showing 12)

• KIAA1543 is a non-centrosomal minus end binding protein. It is termed Nezha(a character in Chinese mythic novel (Journey to the West)). (PMID:19041755)
• The CKK domain binds microtubules and represents a domain that evolved with the metazoa. (PMID:19508979)
• These findings demonstrate that apically localized CAMSAP3 determines the proper orientation of microtubules, and in turn that of organelles, in mature mammalian epithelial cells. (PMID:26715742)
• data suggest that CDH23-C is a CAMSAP3/Marshalin-binding protein that can modify MT networks indirectly through its interaction with CAMSAP3/Marshalin. (PMID:27349180)
• ACF7, a member of the spectraplakin family of cytoskeletal crosslinking proteins, interacts with Nezha (also called CAMSAP3) at the minus ends of noncentrosomal microtubules and anchors them to actin filaments. (PMID:27693509)
• in mammalian intestinal epithelial cells, the spectraplakin ACF7 (also known as MACF1) specifically binds to CAMSAP3 and is required for the apical localization of CAMSAP3-decorated microtubule minus ends. (PMID:27802168)
• CAMSAP3-dependent Golgi vesicle clustering and graded microtubule dynamics (PMID:28089391)
• Findings suggest that CAMSAP3 functions to protect lung carcinoma cells against EMT by suppressing Akt activity via microtubule regulation and that CAMSAP3 loss promotes EMT in these cells. (PMID:30282632)
• Rab14/MACF2 complex regulates endosomal targeting during cytokinesis. (PMID:33566684)
• CAMSAP3 negatively regulates lung cancer cell invasion and angiogenesis through nucleolin/HIF-1alpha mRNA complex stabilization. (PMID:37019300)
• CAMSAP2 and CAMSAP3 localize at microtubule intersections to regulate the spatial distribution of microtubules. (PMID:37567766)
• CAMSAP3, a microtubule orientation regulator, plays a vital role in manifesting differentiation-dependent characteristics in keratinocytes. (PMID:38190868)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	camsap3	ENSDARG00000059475
danio_rerio	CAMSAP3	ENSDARG00000091359
mus_musculus	Camsap3	ENSMUSG00000044433
rattus_norvegicus	Camsap3	ENSRNOG00000000986
drosophila_melanogaster	Patronin	FBGN0263197
caenorhabditis_elegans		WBGENE00004121

Paralogs (2): CAMSAP2 (ENSG00000118200), CAMSAP1 (ENSG00000130559)

Protein

Protein identifiers

Calmodulin-regulated spectrin-associated protein 3 — Q9P1Y5 (reviewed: Q9P1Y5)

Alternative names: Protein Nezha

All UniProt accessions (1): Q9P1Y5

UniProt curated annotations — full annotation on UniProt →

Function. Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization. Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization. Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization. In addition, it also reduces the velocity of microtubule polymerization. Required for the biogenesis and the maintenance of zonula adherens by anchoring the minus-end of microtubules to zonula adherens and by recruiting the kinesin KIFC3 to those junctional sites. Required for orienting the apical-to-basal polarity of microtubules in epithelial cells: acts by tethering non-centrosomal microtubules to the apical cortex, leading to their longitudinal orientation. Plays a key role in early embryos, which lack centrosomes: accumulates at the microtubule bridges that connect pairs of cells and enables the formation of a non-centrosomal microtubule-organizing center that directs intracellular transport in the early embryo. Couples non-centrosomal microtubules with actin: interaction with MACF1 at the minus ends of non-centrosomal microtubules, tethers the microtubules to actin filaments, regulating focal adhesion size and cell migration. Plays a key role in the generation of non-centrosomal microtubules by accumulating in the pericentrosomal region and cooperating with KATNA1 to release non-centrosomal microtubules from the centrosome. Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes. Through interaction with AKAP9, involved in translocation of Golgi vesicles in epithelial cells, where microtubules are mainly non-centrosomal. Plays an important role in motile cilia function by facilitatating proper orientation of basal bodies and formation of central microtubule pairs in motile cilia.

Subunit / interactions. Interacts with PLEKHA7. Interacts with CAMSAP2. Interacts with KATNA1 and KATNB1; leading to regulate the length of CAMSAP3-decorated microtubule stretches. Interacts with AKAP9; regulating Golgi assembly in epithelial cells. Interacts with MACF1. Interacts with AKNA.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Adherens junction. Cilium axoneme. Cilium basal body.

Domain organisation. The CKK domain binds microtubules and specifically recognizes the minus-end of microtubules.

Miscellaneous. ‘Nezha’ is a deity in Chinese mythology.

Similarity. Belongs to the CAMSAP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P1Y5-1	1	yes
Q9P1Y5-2	2

RefSeq proteins (2): NP_001073898, NP_065953* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR011033	PRC_barrel-like_sf	Homologous_superfamily
IPR014797	CKK_CAMSAP	Domain
IPR022613	CH_CAMSAP_2	Domain
IPR031372	CAMSAP_CC1	Conserved_site
IPR032940	CAMSAP	Family
IPR036872	CH_dom_sf	Homologous_superfamily
IPR038209	CKK_dom_sf	Homologous_superfamily
IPR058042	CAMSAP_N	Domain

Pfam: PF08683, PF11971, PF17095, PF25532

UniProt features (46 total): modified residue 17, compositionally biased region 13, region of interest 7, coiled-coil region 3, domain 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P1Y5-F1	60.70	0.23

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 (17): 184, 193, 334, 341, 347, 351, 368, 373, 382, 547, 554, 560, 685, 769, 799, 814, 1074

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_GOLGI_ORGANIZATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_MICROTUBULE_ANCHORING, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (20): DNA replication checkpoint signaling (GO:0000076), microtubule cytoskeleton organization (GO:0000226), in utero embryonic development (GO:0001701), cilium movement (GO:0003341), embryo development ending in birth or egg hatching (GO:0009792), regulation of cell migration (GO:0030334), establishment or maintenance of microtubule cytoskeleton polarity (GO:0030951), regulation of microtubule polymerization (GO:0031113), neuron projection development (GO:0031175), regulation of organelle organization (GO:0033043), microtubule anchoring (GO:0034453), replication fork arrest (GO:0043111), establishment of epithelial cell apical/basal polarity (GO:0045198), zonula adherens maintenance (GO:0045218), regulation of focal adhesion assembly (GO:0051893), regulation of microtubule cytoskeleton organization (GO:0070507), epithelial cell-cell adhesion (GO:0090136), protein transport along microtubule (GO:0098840), regulation of Golgi organization (GO:1903358), cell projection organization (GO:0030030)

GO Molecular Function (7): DNA binding (GO:0003677), calmodulin binding (GO:0005516), spectrin binding (GO:0030507), microtubule minus-end binding (GO:0051011), actin filament binding (GO:0051015), protein binding (GO:0005515), microtubule binding (GO:0008017)

GO Cellular Component (14): cytoplasm (GO:0005737), zonula adherens (GO:0005915), axoneme (GO:0005930), replication fork protection complex (GO:0031298), motile cilium (GO:0031514), ciliary basal body (GO:0036064), microtubule minus-end (GO:0036449), centrosome (GO:0005813), cytoskeleton (GO:0005856), microtubule (GO:0005874), adherens junction (GO:0005912), microtubule cytoskeleton (GO:0015630), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule cytoskeleton organization	3
cellular anatomical structure	3
protein-containing complex binding	2
cytoskeleton	2
cilium	2
microtubule organizing center	2
DNA integrity checkpoint signaling	1
cytoskeleton organization	1
microtubule-based process	1
chordate embryonic development	1
microtubule-based movement	1
embryo development	1
cell migration	1
regulation of cell motility	1
establishment or maintenance of cytoskeleton polarity	1
regulation of microtubule polymerization or depolymerization	1
regulation of protein polymerization	1
microtubule polymerization	1
regulation of supramolecular fiber organization	1
neuron development	1
plasma membrane bounded cell projection organization	1
organelle organization	1
regulation of cellular component organization	1
DNA-templated DNA replication maintenance of fidelity	1
negative regulation of DNA-templated DNA replication	1
polarized epithelial cell differentiation	1
establishment of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
establishment of epithelial cell polarity	1
adherens junction maintenance	1
regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of cell-substrate junction assembly	1
regulation of microtubule-based process	1
regulation of cytoskeleton organization	1
cell-cell adhesion	1
intracellular protein transport	1
transport along microtubule	1
microtubule-based protein transport	1
Golgi organization	1

Protein interactions and networks

STRING

1078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMSAP3	PLEKHA7	Q6IQ23	991
CAMSAP3	KIFC3	Q9BVG8	976
CAMSAP3	MACF1	Q9UPN3	890
CAMSAP3	CTNND1	O60716	835
CAMSAP3	CGNL1	Q0VF96	662
CAMSAP3	NIN	Q8N4C6	567
CAMSAP3	KIF3C	O14782	552
CAMSAP3	NEDD1	Q8NHV4	525
CAMSAP3	CTNNA1	P35221	512
CAMSAP3	CDH1	P12830	511
CAMSAP3	HAUS6	Q7Z4H7	491
CAMSAP3	MEMO1	Q9Y316	490
CAMSAP3	ADAP1	O75689	473
CAMSAP3	MAPRE3	Q9UPY8	462
CAMSAP3	CEP72	Q9P209	444

IntAct

107 interactions, top by confidence:

A	B	Type	Score
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAE	RGS12	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
NS1	PIK3R2	psi-mi:“MI:0914”(association)	0.560
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
MIS12	SPC24	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NCF2	BPGM	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
DCAF7	CLASP2	psi-mi:“MI:0914”(association)	0.510
CAMSAP3	PLEKHA7	psi-mi:“MI:0915”(physical association)	0.460
CAMSAP3	PLEKHA7	psi-mi:“MI:0403”(colocalization)	0.460
CAMSAP3	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
Camsap2	CAMSAP3	psi-mi:“MI:0915”(physical association)	0.400
CAMSAP3	NPM1	psi-mi:“MI:0915”(physical association)	0.400
CAMSAP3	GSK3B	psi-mi:“MI:0915”(physical association)	0.370
TCEAL4	USP11	psi-mi:“MI:0914”(association)	0.350
Cul4a	GPS1	psi-mi:“MI:0914”(association)	0.350
VPS11	GTF2I	psi-mi:“MI:0914”(association)	0.350
Smn1	CLNS1A	psi-mi:“MI:0914”(association)	0.350
ANKFY1	ERAL1	psi-mi:“MI:0914”(association)	0.350
Gbf1	MRPL3	psi-mi:“MI:0914”(association)	0.350
NAF1	C1orf226	psi-mi:“MI:0914”(association)	0.350
LRP8	TYK2	psi-mi:“MI:0914”(association)	0.350
ATXN3	HLA-A	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (160): CAMSAP3 (Proximity Label-MS), CAMSAP3 (Proximity Label-MS), CAMSAP3 (Proximity Label-MS), CAMSAP3 (Proximity Label-MS), CAMSAP3 (Proximity Label-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RR37, A1L170, A1L1I3, A1L260, A2AMM0, A4IFJ0, B5G1P1, D3ZQL6, E7F5E1, G5BQH4, O08919, O54724, O60237, O75420, P06759, P33622, P53814, P85125, Q2KI85, Q2TAL5, Q3T044, Q3UMT1, Q4RTJ5, Q4V882, Q5I1X5, Q5U2R6, Q63312, Q6NZI2, Q75AS0, Q80VC9, Q8BG95, Q8BGT6, Q8C0J6, Q8CI12, Q8IV56, Q8K382, Q8N3F8, Q8TEH3, Q8WUF5, Q91VJ2

Diamond homologs: A1ZAU8, A2AHC3, A5WUN7, D3Z8E6, D4AEC2, Q08AD1, Q5T5Y3, Q6IRN6, Q80VC9, Q8C1B1, Q9P1Y5, U4PAZ9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 122 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
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	67.2×	1e-11
Activation of BAD and translocation to mitochondria	7	66.6×	3e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	58.8×	9e-10
Activation of BH3-only proteins	7	43.5×	9e-09
RHO GTPases activate PKNs	8	31.7×	7e-09
Intrinsic Pathway for Apoptosis	7	25.6×	4e-07
FOXO-mediated transcription	6	25.2×	4e-06
Translocation of SLC2A4 (GLUT4) to the plasma membrane	11	21.2×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	17.4×	3e-03
intracellular protein localization	10	10.0×	6e-05
mitotic cell cycle	7	8.9×	3e-03
microtubule cytoskeleton organization	7	8.1×	4e-03
protein phosphorylation	9	5.8×	4e-03
cell division	12	5.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	171
Likely benign	7
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2583 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7596080:G:GG	donor_gain	1.0000
19:7605214:A:AG	acceptor_gain	1.0000
19:7605214:AT:A	acceptor_gain	1.0000
19:7605215:T:G	acceptor_gain	1.0000
19:7605215:T:TA	acceptor_gain	1.0000
19:7605223:CA:C	acceptor_loss	1.0000
19:7605223:CAG:C	acceptor_gain	1.0000
19:7605224:A:AC	acceptor_loss	1.0000
19:7605224:A:AG	acceptor_gain	1.0000
19:7605224:AGA:A	acceptor_gain	1.0000
19:7605225:G:GG	acceptor_gain	1.0000
19:7605225:GA:G	acceptor_gain	1.0000
19:7605225:GAG:G	acceptor_gain	1.0000
19:7605225:GAGC:G	acceptor_gain	1.0000
19:7605225:GAGCA:G	acceptor_gain	1.0000
19:7605477:ATGGT:A	donor_loss	1.0000
19:7605478:TGGTA:T	donor_loss	1.0000
19:7605480:G:GG	donor_gain	1.0000
19:7605480:GT:G	donor_loss	1.0000
19:7605481:T:G	donor_loss	1.0000
19:7606393:GGTA:G	donor_loss	1.0000
19:7606394:G:T	donor_loss	1.0000
19:7606395:T:A	donor_loss	1.0000
19:7606473:CA:C	acceptor_loss	1.0000
19:7606474:A:AG	acceptor_gain	1.0000
19:7606474:A:AT	acceptor_loss	1.0000
19:7606474:AGACC:A	acceptor_gain	1.0000
19:7606475:G:GA	acceptor_gain	1.0000
19:7606475:GA:G	acceptor_gain	1.0000
19:7606475:GAC:G	acceptor_gain	1.0000

AlphaMissense

7946 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7610524:T:C	L270P	1.000
19:7611881:T:C	L463P	1.000
19:7617580:C:A	N1121K	1.000
19:7617580:C:G	N1121K	1.000
19:7617591:T:A	I1125N	1.000
19:7617599:G:C	A1128P	1.000
19:7617600:C:A	A1128D	1.000
19:7617611:T:C	C1132R	1.000
19:7617613:C:G	C1132W	1.000
19:7617624:G:A	G1136D	1.000
19:7617646:G:C	K1143N	1.000
19:7617646:G:T	K1143N	1.000
19:7617783:T:C	L1159P	1.000
19:7617789:T:C	L1161P	1.000
19:7617792:T:C	F1162S	1.000
19:7617794:C:A	R1163S	1.000
19:7617795:G:C	R1163P	1.000
19:7617798:A:T	D1164V	1.000
19:7617812:T:C	F1169L	1.000
19:7617813:T:C	F1169S	1.000
19:7617814:C:A	F1169L	1.000
19:7617814:C:G	F1169L	1.000
19:7617816:G:C	R1170P	1.000
19:7617824:T:G	Y1173D	1.000
19:7617872:G:A	G1189R	1.000
19:7617872:G:C	G1189R	1.000
19:7617872:G:T	G1189W	1.000
19:7617873:G:A	G1189E	1.000
19:7617885:T:A	V1193D	1.000
19:7617911:T:G	Y1202D	1.000

dbSNP variants (sampled 300 via entrez): RS1000011985 (19:7601494 T>C), RS1000059525 (19:7601884 T>C,G), RS1000184088 (19:7613700 G>T), RS1000223446 (19:7610188 C>T), RS1000239194 (19:7604528 T>C), RS1000742791 (19:7611382 C>A,T), RS1000886161 (19:7613820 C>A,G), RS1000957559 (19:7614044 G>A), RS1000960073 (19:7606206 C>G), RS1001013199 (19:7598732 A>G), RS1001136273 (19:7615231 C>T), RS1001743381 (19:7610097 T>C), RS1001794214 (19:7610388 G>A,T), RS1001921815 (19:7606045 C>T), RS1001974074 (19:7605835 T>G)

Disease associations

OMIM: gene MIM:612685 | disease phenotypes: MIM:613101

GenCC curated gene-disease

Mondo (2): breast ductal adenocarcinoma (MONDO:0005590), familial hemophagocytic lymphohistiocytosis 5 (MONDO:0013135)

Orphanet (1): Familial hemophagocytic lymphohistiocytosis (Orphanet:540)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007637_20	Diffusing capacity of carbon monoxide	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009369	diffusing capacity of the lung for carbon monoxide

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
C567752	Hemophagocytic Lymphohistiocytosis, Familial, 5 (supp.)

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
trichostatin A	affects expression, decreases expression	2
Benzo(a)pyrene	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Nickel	decreases expression	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Aflatoxin B1	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery