HSPB6

Summary

HSPB6 (heat shock protein family B (small) member 6, HGNC:26511) is a protein-coding gene on chromosome 19q13.12, encoding Heat shock protein beta-6 (O14558). Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state.

This locus encodes a heat shock protein. The encoded protein likely plays a role in smooth muscle relaxation.

Source: NCBI Gene 126393 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_144617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26511
Approved symbol	HSPB6
Name	heat shock protein family B (small) member 6
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32389, Hsp20, PPP1R91
Ensembl gene	ENSG00000004776
Ensembl biotype	protein_coding
OMIM	610695
Entrez	126393

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000004982, ENST00000587965, ENST00000592984, ENST00000906439

RefSeq mRNA: 1 — MANE Select: NM_144617 NM_144617

CCDS: CCDS12475

Canonical transcript exons

ENST00000004982 — 3 exons

Exon	Start	End
ENSE00000699587	35755772	35755894
ENSE00001920887	35756811	35757029
ENSE00002780484	35754566	35755683

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 201.3693 / max 5594.1606, expressed in 970 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180578	174.3814	951
180567	16.4873	731
180563	2.5057	513
180560	1.2869	337
180568	1.0255	322
180561	1.0139	320
180562	0.7253	261
180569	0.6695	292
180577	0.5700	222
180573	0.4118	183

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.80	gold quality
apex of heart	UBERON:0002098	99.63	gold quality
gastrocnemius	UBERON:0001388	99.62	gold quality
decidua	UBERON:0002450	99.62	gold quality
right coronary artery	UBERON:0001625	99.55	gold quality
left coronary artery	UBERON:0001626	99.51	gold quality
left uterine tube	UBERON:0001303	99.50	gold quality
endocervix	UBERON:0000458	99.48	gold quality
coronary artery	UBERON:0001621	99.46	gold quality
omental fat pad	UBERON:0010414	99.40	gold quality
popliteal artery	UBERON:0002250	99.32	gold quality
peritoneum	UBERON:0002358	99.32	gold quality
tibial artery	UBERON:0007610	99.32	gold quality
body of uterus	UBERON:0009853	99.30	gold quality
left adrenal gland	UBERON:0001234	99.25	gold quality
left adrenal gland cortex	UBERON:0035825	99.25	gold quality
right adrenal gland cortex	UBERON:0035827	99.24	gold quality
right adrenal gland	UBERON:0001233	99.23	gold quality
ascending aorta	UBERON:0001496	99.23	gold quality
thoracic aorta	UBERON:0001515	99.22	gold quality
aorta	UBERON:0000947	99.21	gold quality
heart left ventricle	UBERON:0002084	99.21	gold quality
cardiac ventricle	UBERON:0002082	99.17	gold quality
right ovary	UBERON:0002118	99.17	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.17	gold quality
right atrium auricular region	UBERON:0006631	99.16	gold quality
diaphragm	UBERON:0001103	99.12	gold quality
left ovary	UBERON:0002119	99.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.07	gold quality
lower esophagus	UBERON:0013473	99.06	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	669.43
E-GEOD-81547	yes	154.48
E-MTAB-6701	yes	138.99
E-ANND-3	yes	27.35
E-GEOD-84465	yes	23.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting HSPB6, 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-4283	100.00	66.42	2097
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311

Literature-anchored findings (GeneRIF, showing 40)

• Our results suggest that a variety of oligomers composed of different proportions of different sHSPs may form in cell types expressing multiple sHSPs. (PMID:16225851)
• Phosphorylation led to changes in actin cytoskeletal morphology in 3T3 cells, delineating strategies for the expression and activation of therapeutic molecules for intracellular protein based therapeutics. (PMID:17084643)
• Interaction of human 14-3-3gamma with the small heat shock protein Hsp20 was analyzed by means of size-exclusion chromatography and chemical crosslinking. (PMID:17109079)
• Data support a novel role for pHSP20 in the modulation of cyclic-nucleotide-mediated myometrial relaxation, through interaction with actin. pHSP20 represents an important new target for future tocolytic therapy. (PMID:18755793)
• AZX100, an analogue of the small heat shock protein, HSP20, reduces TGF-beta1-induced CTGF expression in keloid fibroblasts (PMID:18787533)
• Human mutation in the anti-apoptotic heat shock protein 20 abrogates its cardioprotective effects (PMID:18790732)
• Promoter methylation and differential gene expression of five markers: COL1A2, NPM2, HSPB6, DDIT4L and MT1G were validated by sequencing of bisulfite-modified DNA and real-time reverse transcriptase PCR, respectively. (PMID:19491193)
• Here, crystal structures of excised alpha-crystallin domain from rat Hsp20 and that from human alphaB-crystallin show that they form homodimers with a shared groove at the interface by extending a beta sheet. (PMID:19646995)
• Data show that the interaction between HspB6 and Bag3 requires the same regions that are involved in the HspB8-Bag3 association. (PMID:19845507)
• Report increased levels of phosphorylated Hsp20 in failing hearts. (PMID:19850943)
• The 14-3-3 zeta mutation mimicking phosphorylation of Ser184 does not markedly affect interaction with tau protein and improves the interaction of 14-3-3 zeta with HspB6. (PMID:21081103)
• Nevertheless, in solution, both alpha-crystallin domain proteins form stable dimers via the symmetric antiparallel interaction of beta7 strands. (PMID:21641913)
• Overexpression of HSPB1, as well as HSPB6, HSPB7 and HSPB8 independently protect against tachycardia remodeling by attenuation of the RhoA GTPase pathway at different levels. (PMID:21731611)
• A potential molecular mechanism by which Hsp20 acetylation can affect myometrial activity by liberating cofilin (PMID:21803775)
• Properties of the monomeric form of 14-3-3zeta protein and its interaction with tau and HspB6. This interaction requires phosphorylation of tau protein and HspB6. (PMID:21978388)
• Hsp20 serves as a novel cardiokine in regulating myocardial angiogenesis through activation of the VEGFR signaling cascade. (PMID:22427880)
• cofilins 1 and 2 only weakly interact with 14-3-3 and therefore cannot directly compete with phosphorylated small heat shock protein HspB6 for its binding to 14-3-3 (PMID:22450169)
• the cytosolic protein AKAP-Lbc (AKAP13) as the anchoring protein responsible for directing PKA phosphorylation of Hsp20 on Ser(16) (PMID:22731613)
• 14-3-3zeta and possibly other 14-3-3 isoforms may have additional functional roles conducted by the monomeric state (PMID:22794279)
• HSP20 directly associates with PI3K subunits and suppresses its activity in hepatocellular carcinoma, resulting in the inhibition of the AKT pathway, and subsequently decreasing the growth of hepatocellular carcinoma. (PMID:24223153)
• Findings strongly suggest that HSP20 directly associates with Bax and stimulates caspase cascade in human hepatocellular carcinoma cells. (PMID:24969689)
• Data suggest that heat shock protein 20 (HSP20) may have value as a prognostic tumor marker and its overexpression might be a novel strategy for colorectal cancer (CRC) therapy. (PMID:25187324)
• peptides in heat-shock protein Hsp20 (G71HFSVLLDVKHFSPEEIAVK91) and Hsp27 (D93RWRVSLDVNHFAPDELTVK113) with sequence homology to alpha-crystallin also have robust chaperone and anti-apoptotic activities. (PMID:25332102)
• HSP20 may play a protective role against the progression of ovarian cancer. (PMID:25423708)
• These findings strongly suggest that HSP20 might decrease the IKK-alpha protein level and that it down-regulates the TNF-alpha-stimulated intracellular signaling in HCC, thus resulting in the suppression of HCC progression. (PMID:25447820)
• N-terminal mutations increase stability of large HspB1 homooligomers, prevent their phosphorylation-dependent dissociation, modulate their interaction with HspB6 and decrease their chaperoning capacity, preventing normal functioning of HspB1. (PMID:25965061)
• multiple sclerosis lesions revealed exclusive induction of HSPB6 in astrocytes, as confirmed by co-localization of HSPB6 with GFAP. (PMID:26694816)
• findings strongly suggest that phosphorylated HSP20 inhibits TGF-alpha-induced HCC cell migration and invasion via suppression of the JNK signaling pathway (PMID:27046040)
• Structural basis for the interaction of a human HSPB6 protein with the 14-3-3 universal signaling regulator has been reported. (PMID:28089448)
• Data suggest that HSPB6 forms hetero-oligomers with HSPB1 under the following rules: (1) highly conserved motif RLFDQXFG is necessary for subunit exchange among oligomers, (2) a site about 20 residues downstream of this motif determines size of resultant hetero-oligomers, and (3) a region in the N-terminal domain that is unique to HSPB6 dictates preferential formation of heterodimers. (HSP = heat shock protein) (PMID:28487364)
• these findings reveal a new regulatory mechanism of HSPB6 in cell survival through its interaction with BECN1. (PMID:29157081)
• HSP20 affects the invasiveness of extravillous trophoblast cells via Akt signaling pathway, and the its dysregulation might contribute to the pathophysiology of pre-eclampsia. (PMID:30305007)
• Effect of Arginine on Chaperone-Like Activity of HspB6 and Monomeric 14-3-3zeta. (PMID:32188159)
• Physico-chemical properties of two point mutants of small heat shock protein HspB6 (Hsp20) with abrogated cardioprotection. (PMID:32353387)
• Prevalence of HSPB6 gene variants in peripartum cardiomyopathy: Data from the German PPCM registry. (PMID:36918127)
• HSPB6 Is Depleted in Colon Cancer Patients and Its Expression Is Induced by 5-aza-2’-Deoxycytidine In Vitro. (PMID:37241227)
• Cellular functions of heat shock protein 20 (HSPB6) in cancer: A review. (PMID:37844714)
• Overexpression of HSPB6 inhibits osteosarcoma progress through the ERK signaling pathway. (PMID:37861934)
• HSPB6 Deficiency Promotes the Development of Aortic Dissection and Rupture. (PMID:38237739)
• Inhibition of HSP20 Ameliorates Steatotic Liver Disease by Stimulating ERK2-Dependent Autophagy. (PMID:38466834)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspb6	ENSDARG00000077236
mus_musculus	Hspb6	ENSMUSG00000036854
rattus_norvegicus	Hspb6	ENSRNOG00000020922
drosophila_melanogaster	Hsp27	FBGN0001226
caenorhabditis_elegans		WBGENE00002011
caenorhabditis_elegans		WBGENE00002015
caenorhabditis_elegans		WBGENE00002016
caenorhabditis_elegans		WBGENE00002017
caenorhabditis_elegans		WBGENE00002018
caenorhabditis_elegans		WBGENE00002019
caenorhabditis_elegans		WBGENE00002020
caenorhabditis_elegans		WBGENE00008591
caenorhabditis_elegans		WBGENE00008592
caenorhabditis_elegans	hsp-12.1	WBGENE00011906

Paralogs (8): HSPB1 (ENSG00000106211), CRYAB (ENSG00000109846), HSPB8 (ENSG00000152137), CRYAA (ENSG00000160202), HSPB3 (ENSG00000169271), HSPB2 (ENSG00000170276), HSPB7 (ENSG00000173641), HSPB9 (ENSG00000260325)

Protein

Protein identifiers

Heat shock protein beta-6 — O14558 (reviewed: O14558)

Alternative names: Heat shock 20 kDa-like protein p20, Heat shock protein family B member 6

All UniProt accessions (4): O14558, A0A1X7SC65, K7EP04, V9HWB6

UniProt curated annotations — full annotation on UniProt →

Function. Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state. Seems to have versatile functions in various biological processes. Plays a role in regulating muscle function such as smooth muscle vasorelaxation and cardiac myocyte contractility. May regulate myocardial angiogenesis implicating KDR. Overexpression mediates cardioprotection and angiogenesis after induced damage. Stabilizes monomeric YWHAZ thereby supporting YWHAZ chaperone-like activity.

Subunit / interactions. Homodimer. Small heat shock proteins form high molecular mass oligomers containing variable number of monomers; these oligomers display a very flexible quaternary structure easily exchanging their subunits. Heterooligomer with HSPB1; formed through oligomerization of HSPB1:HSBP6 dimers; subunit exchange leads to formation of at least two different heterooligomeric complexes, differing in variable quantities of HSPB1 and HSPB6 homodimers in addition to HSPB1:HSPB6 heterodimers. Heterooligomer with CRYAB; large heterooligomers consist of CRYAB homodimers and HSPB5:HSPB6 heterodimers but lacking HSPB6 homodimers. Interacts with BAG3. Interacts (phosphorylated) with YWHAZ. Interacts with PDE4A and PDE4D; required for maintenance of the non-phosphorylated state of HSPB6 under basal conditions. Interacts with KDR. Interacts with PRKD1.

Subcellular location. Cytoplasm. Nucleus. Secreted.

Post-translational modifications. The N-terminus is blocked. Phosphorylated at Ser-16 by PKA and probably PKD1K; required to protect cardiomyocytes from apoptosis.

Similarity. Belongs to the small heat shock protein (HSP20) family.

RefSeq proteins (1): NP_653218* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001436	Alpha-crystallin/sHSP_animal	Family
IPR002068	A-crystallin/Hsp20_dom	Domain
IPR003090	Alpha-crystallin_N	Domain
IPR008978	HSP20-like_chaperone	Homologous_superfamily

Pfam: PF00011, PF00525

UniProt features (22 total): strand 9, mutagenesis site 4, helix 2, modified residue 2, chain 1, domain 1, sequence conflict 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
4JUT	X-RAY DIFFRACTION	2.2
5OK9	X-RAY DIFFRACTION	2.35
5LU1	X-RAY DIFFRACTION	2.4
4JUS	X-RAY DIFFRACTION	2.5
5LU2	X-RAY DIFFRACTION	2.5
5LUM	X-RAY DIFFRACTION	2.6
5OKF	X-RAY DIFFRACTION	3.2
5LTW	X-RAY DIFFRACTION	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14558-F1	75.05	0.46

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 (2): 16, 66

Mutagenesis-validated functional residues (4):

Position	Phenotype
3	increases homodimer-based self-association properties; increases chaperone activity; when associated with g-5.
5	increases homodimer-based self-association properties; increases chaperone activity; when associated with g-3.
67	no effect on homodimer-based self-association properties; no effect on chaperone activity.
134	decreases heteromer formation with cryab.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, CAGCTG_AP4_Q5, AACWWCAANK_UNKNOWN, BROWNE_HCMV_INFECTION_48HR_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_APOPTOTIC_PROCESS, GOBP_PROTEIN_MATURATION, AP1_Q4_01, GOBP_BLOOD_VESSEL_MORPHOGENESIS, MODULE_99, TGANTCA_AP1_C, GOBP_PROTEIN_FOLDING, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, CREB_Q3

GO Biological Process (6): protein folding (GO:0006457), response to heat (GO:0009408), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), protein refolding (GO:0042026), negative regulation of apoptotic process (GO:0043066), positive regulation of angiogenesis (GO:0045766)

GO Molecular Function (6): structural constituent of eye lens (GO:0005212), protein kinase binding (GO:0019901), protein homodimerization activity (GO:0042803), protein folding chaperone (GO:0044183), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087)

GO Cellular Component (6): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein folding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular process	1
protein maturation	1
response to stress	1
response to temperature stimulus	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
structural molecule activity	1
kinase binding	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
protein binding	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1506 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPB6	HSPA4	P34932	835
HSPB6	BAG3	O95817	827
HSPB6	HSPD1	P10809	790
HSPB6	HSPB1	P04792	770
HSPB6	SHQ1	Q6PI26	766
HSPB6	DNAJB1	P25685	765
HSPB6	HSP90AA1	P07900	726
HSPB6	HSP90AB1	P08238	726
HSPB6	TSG101	Q99816	702
HSPB6	YWHAZ	P29213	697
HSPB6	HSPB9	Q9BQS6	685
HSPB6	YWHAG	P35214	663
HSPB6	SP100	P23497	662
HSPB6	HSPE1	P61604	632
HSPB6	HSPB8	Q9UJY1	619

IntAct

9 interactions, top by confidence:

A	B	Type	Score
HSPB6	BAG3	psi-mi:“MI:0914”(association)	0.530
YWHAG	HSPB6	psi-mi:“MI:0914”(association)	0.530
HSPB6	YWHAG	psi-mi:“MI:0914”(association)	0.530
HSPB6	HSPB8	psi-mi:“MI:0915”(physical association)	0.450
HSPB8	HSPB6	psi-mi:“MI:2364”(proximity)	0.450
E4	MCRIP1	psi-mi:“MI:0914”(association)	0.350
ezrA	HSPB6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): MAP1B (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), PNMA2 (Affinity Capture-MS), BAG3 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), ATG4A (Affinity Capture-MS), PNMA2 (Affinity Capture-MS), MAP1B (Affinity Capture-MS), BAG3 (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), HSPB6 (Reconstituted Complex), FBXO11 (Affinity Capture-MS)

ESM2 similar proteins: E2RDP2, O14526, O14558, O15197, O35878, O95382, P02512, P04792, P0C0K6, P0C5W1, P14602, P15991, P42929, P42930, P97541, Q00649, Q08DM2, Q13470, Q148F8, Q16082, Q2KHU9, Q2KIR4, Q3T033, Q3T149, Q4VYA0, Q5EBG6, Q5JR98, Q5JZY3, Q5RE82, Q5S1U1, Q6F5E8, Q6NY19, Q6P9Q4, Q6SJQ8, Q6ZW31, Q8C052, Q8CDY7, Q8N5L8, Q8TBH0, Q8TDZ2

Diamond homologs: A5JV83, O14558, P02487, P02488, P02489, P02507, P02510, P02511, P02512, P04120, P04792, P05811, P06581, P06582, P14602, P15991, P23927, P23928, P30218, P30219, P34696, P35385, P41316, P42929, P42930, P42931, P82147, P97541, Q00649, Q04757, Q05557, Q05713, Q148F8, Q1RI96, Q3T149, Q5EAC9, Q5ENY9, Q5R9K0, Q5RAB0, Q5S1U1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	down-regulates	HSPB6	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

583 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35755766:GCTCA:G	donor_loss	1.0000
19:35755767:CTCA:C	donor_loss	1.0000
19:35755769:CAC:C	donor_loss	1.0000
19:35755770:A:AC	donor_gain	1.0000
19:35755770:A:AG	donor_loss	1.0000
19:35755771:C:CA	donor_loss	1.0000
19:35755771:C:CC	donor_gain	1.0000
19:35755903:A:T	acceptor_gain	1.0000
19:35756807:GCACC:G	donor_loss	1.0000
19:35756809:ACC:A	donor_loss	1.0000
19:35756810:C:A	donor_loss	1.0000
19:35755680:CATC:C	acceptor_gain	0.9900
19:35755771:CCGGG:C	donor_gain	0.9900
19:35755894:CCTGA:C	acceptor_loss	0.9900
19:35755895:C:G	acceptor_loss	0.9900
19:35755900:C:CT	acceptor_gain	0.9900
19:35755902:C:CT	acceptor_gain	0.9900
19:35755681:ATCC:A	acceptor_loss	0.9800
19:35755682:TCC:T	acceptor_loss	0.9800
19:35755683:CCT:C	acceptor_loss	0.9800
19:35755684:C:CC	acceptor_gain	0.9800
19:35755684:CTGGA:C	acceptor_loss	0.9800
19:35755685:T:C	acceptor_loss	0.9800
19:35755868:C:CT	acceptor_gain	0.9800
19:35755895:C:CC	acceptor_gain	0.9800
19:35755909:C:CT	acceptor_gain	0.9800
19:35756760:AGACC:A	donor_gain	0.9800
19:35756796:C:A	donor_gain	0.9800
19:35756800:AGG:A	donor_gain	0.9800
19:35755682:TC:T	acceptor_gain	0.9700

AlphaMissense

999 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35755574:A:T	I144N	1.000
19:35755655:A:G	F117S	1.000
19:35755824:A:T	V90D	1.000
19:35755844:G:C	F83L	1.000
19:35755844:G:T	F83L	1.000
19:35755845:A:G	F83S	1.000
19:35755846:A:G	F83L	1.000
19:35755574:A:G	I144T	0.999
19:35755644:A:C	Y121D	0.999
19:35755650:G:T	R119S	0.999
19:35755654:G:C	F117L	0.999
19:35755654:G:T	F117L	0.999
19:35755656:A:G	F117L	0.999
19:35755667:A:T	V113D	0.999
19:35755673:C:T	G111E	0.999
19:35755791:G:T	A101E	0.999
19:35755830:A:T	I88N	0.999
19:35755845:A:C	F83C	0.999
19:35755846:A:C	F83V	0.999
19:35755846:A:T	F83I	0.999
19:35755860:A:G	L78P	0.999
19:35755574:A:C	I144S	0.998
19:35755580:A:G	L142P	0.998
19:35755580:A:T	L142Q	0.998
19:35755587:C:G	G140R	0.998
19:35755655:A:C	F117C	0.998
19:35755662:G:T	R115S	0.998
19:35755673:C:A	G111V	0.998
19:35755674:C:G	G111R	0.998
19:35755674:C:T	G111R	0.998

dbSNP variants (sampled 300 via entrez): RS1000309698 (19:35757631 T>C), RS1000338983 (19:35757363 CT>C), RS1000726103 (19:35758288 C>T), RS1001557310 (19:35757740 T>G), RS1002502974 (19:35756793 C>A,G), RS1002846349 (19:35756058 T>A), RS1003196488 (19:35757320 C>T), RS1003786289 (19:35755299 G>A), RS1004198414 (19:35757852 T>C,G), RS1004683547 (19:35756586 A>G), RS1004843934 (19:35756896 A>C,G), RS1005340898 (19:35756998 G>A), RS1005618052 (19:35756832 G>A,C), RS1005845938 (19:35755601 G>A,T), RS1008742681 (19:35757395 C>G)

Disease associations

OMIM: gene MIM:610695 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_277	Brain morphology (MOSTest)	2.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	increases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	increases methylation, affects cotreatment	1
trimellitic anhydride	decreases expression	1
bisphenol B	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
incobotulinumtoxinA	increases expression	1
N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Bleomycin	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression, increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Acrylamide	decreases 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